Transplanted pig heart works differently in humans, here is the proof

In January this year, the heart of a genetically modified pig was transplanted into a human for the first time. The patient, David Bennett, managed to survive for two months with the pig heart, and this unique organ transplant operation led to various exciting findings and further research work.

One recently published research reveals that the electrical conduction system (network of cells, signals, and nodes in a heart that collectively controls heart functions and heartbeat) of the genetically modified pig heart differs from that of an ordinary pig’s heart. The findings are based on the ECG (electrocardiogram) readings of the pig heart transplanted to David Bennett.

Differences measured by the ECG

After successful transplantation, the electrical conduction system of the transplanted pig heart was monitored using a 12-lead ECG. The researchers studied the ECG data recorded after one day of the xenotransplant operation (organ transplantation in which the donor and recipient are of different species). They examined factors such as the QT interval, the PR interval, and the QRS complex.

The former indicates the time electric current takes to travel from the heart's lower chamber to perform a complete cycle. Whereas PR and QRS denote the time, electricity goes from the top chamber to the lower chamber of the heart. Both these parameters are associated with the movement of electric current through the heart during a heartbeat.

The researchers started out expecting that the xenotransplant may behave the same way that pig hearts usually behave. Electricity travels quickly from the top to the bottom chamber (due to some well-described anatomic differences between the pig heart and the human heart). This allows the pig heart to go through a full heartbeat cycle faster than the human heart.

“We expected to see that in the xenotransplant as well: that the timing intervals on the 12-lead ECG would be faster than what we typically see in human hearts. However, the timing intervals were longer, not only as long as typically in humans but even longer than that,” one of the authors and cardiologist at the University of Maryland Medical Center (UMMC), Dr. Timm Dickfeld told IE.

The PR, QRS, and QT time intervals for the heart of a normal pig inside a pig's body range between 50-120 milliseconds (ms), 70-90 ms, and 260-380 ms, respectively. Whereas for the genetically modified pig heart inside the human patient, the PR, QRS, and QT times were 190 ms, 138 ms, and 538 ms, respectively. The researchers also noticed prolonged PR and QRS intervals for some time in the ECG readings taken later.

What do these differences in the ECG suggest?

The researchers believe that the current study's findings would allow them to understand the various complexities of xenotransplantation. The differences in ECG readings highlight the impact of xenotransplantation on the heart’s electrical conduction system, and these results could enable us to increase the success rate of future xenotransplant operations.

Even now, thousands of US patients are waiting to have their hearts transplanted. Xenotransplants could end their wait, but before that, doctors and scientists need to understand this approach's various aspects and outcomes.

Explaining this further, Dr. Dickfeld wrote, “The ultimate goal is that if someone needs a heart, xenotransplantation may be an option. 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.”

Currently, the researchers are also looking into several possible explanations for why the differences in the heart's electrical activity exist in the first place. One of the reasons could be that xenotransplant results in a pig's heart functioning without the pig’s body. So most of the innervation that provides input from the pig’s brain toward the pig’s body is missing.

The researchers suggest denervation in human hearts can also have long-lasting effects on some heart functions. Secondly, the patient got many different medications to make sure that the transplant did not get rejected or that no infections would happen. Some of those medications are novel, and very little is known about potential effects on the ECG criteria.

Additionally, a variety of substances that the heart is subjected to before transplantation may affect the ECG findings. Plus, the effects of how the human body, with all its circulating human molecules and a pig’s organ, work together is also not known. The authors are exploring multiple such hypotheses.

However, the results of the current study are based on only one xenotransplant. So more studies are required to be conducted to further confirm the above-mentioned theories' validity.

The study will be presented at the American Heart Association’s Scientific Sessions 2022.