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

Research highlights:

• Electrocardiogram (ECG) measurements performed after the first pig-to-human heart transplantation showed that the electrical conduction properties were significantly different compared to those found in native porcine hearts (porcine hearts transplanted into pigs). It turned out to be very different.
• Common ECG readings are usually shorter in pigs than in humans, but the January 2022 pig-to-human heart transplant unexpectedly made these ECG readings longer.

embargo until 4am (CT/5am) E.T. October 31, 2022 (Monday)

DALLAS, OCTOBER 31, 2022 — Electrocardiographic heart rhythm measurements of the first pig-to-human heart transplant show predictive benefits for the electrical conduction system of genetically engineered porcine hearts compared to unmodified porcine hearts. I could see the difference outside. It will be presented at the American Heart Association Scientific Sessions 2022. Held in person from November 5-7, 2022 in Chicago and held online, the conference is the premier venue for sharing the latest scientific advances, research, and evidence-based clinical practice updates globally. is. cardiovascular science.

Xenotransplantation — the process of transplanting organs from one animal species into another — is January 2022, when a 57-year-old man with terminal heart disease received the first ever genetically modified pig heart transplant. The patient survived for 61 days.

Researchers have been working on this new pig-to-human transplant technology for more than 30 years. If successful, harvesting hearts from transgenic pigs that have been genetically altered so that they can be safely transplanted into humans could one day become a reality.

“There are several potential challenges in transplanting pig hearts into humans. is an arrhythmia and that’s where the electrocardiogram (ECG) comes in,” said Tim Dickfeld, M.D. D. is Professor of Medicine and Director of Electrophysiology Research at the University of Maryland School of Medicine, Baltimore. “It is truly a novel finding that the ECG parameters of pig hearts after being transplanted into humans were very different compared to those commonly found in wild pig hearts.”

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

Specifically, researchers identified two ECG measurements: the PR interval/QRS complex and the QT interval. The PR interval and QRS complex measure the time it takes for electricity to travel from the upper heart to the lower ventricle and pump blood across the lower ventricle. The QT interval measures the time it takes for the lower chambers of the heart to go through a complete electrical cycle associated with the heartbeat.

For this study, ECG data of transplant patients were collected typically once a day after transplantation. In previous studies, porcine heart ECG parameters in pigs have short PR intervals (50–120 ms), short QRS (70–90 ms), and short QT (260–380 ms). was shown.

“In contrast, the first-ever electrocardiogram of a transgenic heart xenograft found a long PR interval of 190 ms, a QRS duration of 138 ms, and a QT of 538 ms. It’s longer than you’d expect from a pig’s heart, body,” said Dick Feld.

“In the human heart, prolonged periods of these parameters may indicate electrical or myocardial disease,” he said. “The electrocardiographic parameters of the pig heart extended to those found in the human heart, and in many cases the measurements extended beyond what is considered normal in the human heart.”

Furthermore, continuous ECG measurements show that the prolonged PR interval is stable after implantation, averaging around 210 ms. QRS duration remained prolonged by approximately 145 ms, but these shortened later in the 61 days post-implantation.

“For example, if the muscles or the electrical system itself are diseased, the QRS may last longer. So the electricity can travel from cell to cell, moving from one side of the heart to the other. It takes a long time,” said Dickfeld. “Generally, this he wants to avoid prolonged QRS readings.”

Finally, this study revealed an increase in QT duration of approximately 509 ms on average with dynamic fluctuations. The lowest QT duration was observed on his 14th day. “Prolonged QT measurements were a concern in our patient. Despite some variability, QT measurements remained prolonged throughout his 61 days.”

The researchers believe that these findings provide a basis for future studies to better understand the effects of xenotransplantation on the heart’s electrical system and prepare for future xenotransplantation cases.

According to the American Heart Association, in 2020 (latest data available), the United States had the highest number of heart transplants, with 3,658 heart transplants performed. 2022 heart disease and stroke statistics updateAs of February 2021, 3,515 people were on the waiting list for heart transplants and 49 were on the waiting list for heart and lung transplants, according to an update.

“The ultimate goal is that if someone needs a heart, xenotransplantation might be an option,” Dickfeld said. We need to make it viable, in the areas of rejection, infections, pump problems and definitely abnormal electrical signals and heart rhythms.”

A major limitation is that this study is the first to include a single patient. Future research will give us a better base of knowledge to build on.

“This was a real milestone in research on xenotransplantation, the transplantation of organs from one species to another, in this case from pigs to humans. There were steps, but they were mostly centered around genetic manipulation to reduce organ rejection, and solving the rejection problem would ultimately lead to this method being used to help many patients with progressive heart failure. Professor of Medicine and Biotechnology at Stanford University and Editor-in-Chief of the Journal of the American Heart Association Circulation: arrhythmias and electrophysiology.

“It is of great interest to understand the factors that influence the parameter changes observed by comparing Pig-in-Pig and Pig-in-Human values, such as rejection and hemodynamic status. “Further analysis of the electrocardiogram, including ST-T wave abnormalities, may also provide unique insights.” ”

Co-authored by Calvin Kagan, MD. Richard Sandeep Amara MD. Dr. Muhammad Haq M.D. Muhammad Mohiuddin, MBBS. Susie N. Hong-Zohlman, MD. Mandurah Ananslam, MBBS. Charles C. Hong, MD, Ph.D.; Vincent Y. See, MD. Stephen Shorofsky, MD, Ph.D. and Bartley Griffith, MD Author disclosures are in the abstract.

The study authors report no external funding sources.

Research statements and conclusions presented at an American Heart Association scientific conference are solely those of the study authors and do not necessarily reflect the policies or positions of the association. The Association makes no representations or warranties as to their accuracy or reliability. Abstracts presented at the Society’s scientific meetings are not peer-reviewed. Rather, they are curated by an independent review board and considered on the basis of their potential to add to the diversity of scientific issues and views discussed at the conference. Findings are considered preliminary until publication as a full manuscript in a peer-reviewed scientific journal.

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