We’re getting closer to understanding why the man who received the first pig heart transplant or Xenotransplantation, passed away after 61 days.

When a 57-year-old man with fatal heart disease underwent the first-ever transplant of a genetically modified pig heart in January 2022, xenotransplantation – the technique of implanting an organ from one animal species to another – took a significant step forward. The patient survived for 61 days.

For more than 30 years, scientists have been developing this novel pig-to-human transplantation method. If successful, genetically modified pigs’ hearts, whose genes have been changed so they may be safely transplanted to people, could one day be harvested for human use.

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

After a heart transplant, ECG monitoring is one approach to evaluate the electrical conduction system. A 12-lead ECG monitors the electrical conduction of the heart at 12 distinct electrical angles.

Researchers specifically looked at the PR interval/QRS complex and the QT interval, two ECG measurements. The PR interval and QRS complex measure the amount of time it takes for electricity to move from the top chamber to the bottom chamber and across the bottom chambers, thus pumping blood through the heart.

The QT interval counts the number of beats it takes the lower chambers of the heart to complete one complete electrical cycle.

The ECG data of the transplant patient were gathered for this study once a day after the transplant. Previous studies showed that the pig heart’s ECG characteristics exhibited short PR intervals (50 to 120 milliseconds), short QRS intervals (70 to 90 milliseconds), and short QT intervals (260 to 380 milliseconds).

“In contrast, the first-ever ECG of a genetically modified heart xenotransplant found a longer PR interval of 190 milliseconds, QRS duration of 138 milliseconds and QT of 538 milliseconds, which is longer than what would be expected from a pig heart in a pig body,” Dickfeld adds.

“In a human heart, when those parameters get longer,” as explained by the professor, “this can indicate signs of electrical or myocardial disease.

“The pig heart ECG parameters were extended to what we see in a human heart and often the measures even extended beyond what we consider normal in a human heart.”

Additionally, the ongoing ECG measurements show that prolonged PR intervals averaged about 210 milliseconds following the transplant and remained constant. During the 61-day post-transplant period, the QRS length remained prolonged at around 145 milliseconds, but decreased subsequently.

“The QRS duration may prolong when, for example, the muscle and the electrical system itself is diseased, and that is why it takes a long time for electricity to travel from cell to cell and travel from one side of the heart to the other,” Dickfeld adds. “In general, we would prefer for this QRS measure not to prolong too much.”

In conclusion, the study demonstrated an elevated QT duration of around 509 milliseconds with dynamic changes. Day 14 saw the lowest QT duration recorded.

“In the human heart, the QT duration is correlated with an increased risk of abnormal heart rhythms,” highlights Dickfeld. “In our patient, it was concerning that the QT measure was prolonged. While we saw some fluctuations, the QT measure remained prolonged during the whole 61 days.”

The findings, in the opinion of the researchers, lay the groundwork for future studies to better comprehend the effects of xenotransplantation on the heart’s electrical system and to better prepare for xenotransplantation instances in the future.

According to the American Heart Association’s 2022 Heart Disease and Stroke Statistical Update, the United States had the highest number of heart transplants performed with 3,658 transplants in 2020 (the most current data available).

As of February 2021, the update said that 3,515 people were waiting for a heart transplant and 49 people were waiting for a heart and lung transplant.

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

This is the first study of its kind, and it only involved one patient, which is a major downside.

Future research will be able to build on a better base of known facts.

Image Credit: Getty

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