The death of the world’s first pig heart transplant patient is deeply regrettable, and there are many questions about the cause of death.
According to the University of Maryland website reported on June 30, after a year of research, the famous medical journal The Lancet published a case report on the operation, giving the latest conclusions on the analysis of the reasons for failure.
The first pig heart transplant patient died two months later
The Lancet published the reasons for the failure
On July 2, comprehensive News, Global Science and Technology reported that in January 2022, physicians at the University of Maryland School of Medicine performed the world’s first genetically modified pig heart transplant, and a 57-year-old Maryland man received a “gene-edited pig heart transplant.”
The man received the world’s first genetically modified pig heart transplant because he was bedridden and on machine support, making him unfit for a human heart transplant, Xinhua reported earlier. The University of Maryland Medical Center implanted the pig heart after receiving emergency authorization from U.S. regulators and the patient’s consent.
The genetically modified pigs were supplied by Levi-Vicor, a biotech company based in Virginia.
In the first few weeks after the transplant, the man showed no signs of acute rejection. But two months after the transplant, the man suddenly died of heart failure.
The surgeon (left) and the transplant patient (right: University of Maryland Medical Center)
Since then, the transplant team has studied the causes of heart failure in patients after surgery. Mohammed Mohiuddin, professor of surgery and director of the Heart Xenotransplantation program at the University of Maryland School of Medicine, and Bartley Griffiths, a pig heart transplant surgeon, are the study’s lead authors.
The new study, published in The Lancet, confirms that there may be a combination of factors contributing to heart failure in patients.
First, the patient had extensive endothelial damage, indicating the presence of antibody-mediated rejection. The patient was in poor health before the transplant, resulting in his severely compromised immune system, which also limited the use of effective anti-rejection protocols used in preclinical studies of transplants. As a result, the patients’ organs may be more susceptible to rejection by antibodies produced by the immune system, the researchers found.
Then, patients treated with intravenous immunoglobulin (IVIG) – a drug containing antibodies – after transplantation may also cause damage to heart muscle cells. In the second month after the transplant, the patient received two injections to help prevent infection and may also trigger an immune-activated response to the pig heart.
Finally, the new study suggests that latent viruses of porcine cytomegalovirus/Porcine roseola virus (PCMV/PRV) may be present in xenografted pig hearts, which could lead to graft dysfunction. After the patient reduced the antiviral regimen, the virus may have been activated, possibly triggering an inflammatory response that led to cell damage. However, there is no evidence that the virus infected patients or spread to organs other than the heart.
Previously, on June 22, 2022, the medical journal NEJM published for the first time the results of the world’s first study of pig heart transplant patients, believing that the patient’s heart autopsy results were inconsistent with typical xenograft rejection. The MIT Technology Review reported on May 4, 2022 that the cause of death may have been the presence of the virus in the transplanted pigs.
“We hope that the next patient will not only survive longer with the transplant, but will be able to return to a normal life for months or even years,” Griffiths said.
There is a severe global shortage of transplanted organs
The scientists decided to change tack
Although the world’s first pig heart transplant ended in failure, it still opened the imagination of all kinds of organ transplants.
According to a Xinhua report last year, the United States will perform more than 41,000 organ transplants in 2021, a record, including about 3,800 heart transplants. However, the gap between supply and demand for organs is huge. There are more than 106,000 people on the national organ waiting list in the United States, and thousands of patients die each year waiting for organs.
“The main difficulty of heart transplantation is the shortage of heart transplant donors, which is in contradiction with the large number of patients with advanced heart failure who need to receive heart transplants,” Shanghai Wenwei Po previously reported. Professor Zhao Qiang, vice president of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and an expert in cardiac surgery, said of the organ shortage by analyzing the case in the United States, “At present, there is a serious shortage of transplanted organs worldwide, and people die every day while waiting. In China, there are as many as 1.5 million patients with advanced heart failure every year, but about 500 to 600 patients can actually receive transplants.”
Professor Zhao Qiang said that from the technical point of view, the heart transplant is basically no difficulty, the success rate of the operation is more than 95%, and the survival rate of one year after the operation is as high as 94-95%. The first heart transplant in China, and also the first in Asia, was performed in Ruijin Hospital in 1978. Since then, heart transplants have been carried out continuously in China, and there are reports of patients surviving for more than 20 years after transplantation.
So the question is, where does the heart come from? “To solve the shortage of transplanted organs, scientists have turned their attention to animal organs.” Professor Zhao Qiang said.
The medical community has long been interested in xenotransplantation, with experiments dating back to the 17th century. Early research focused on obtaining organs from primates, but in recent years the focus has shifted to pigs.
Most xenotransplants fail because the recipient quickly rejects them. The pig heart implanted in the man came from a genetically modified pig, which is also the genetic modification program mentioned in the pig heart report. Scientists removed genes that cause rapid rejection in pigs and added human genes to make pig organs better accepted.
“Rejection” is the difficulty that organ transplant engineering needs to face. In short, the body’s immune system may reject foreign tissues or organs, and the results of this reaction can be small or large, and can be fatal. Scientists genetically modified pigs to suppress these rejections and prevent the patient’s immune system from attacking the pig’s heart.
“Pig hearts are similar in size to human hearts, but from the point of origin of species, it is far different from humans, so zoonotic diseases are less. With the development of gene editing technology, scientists can cut out the gene expression of pigs and transfer human genes into pig hearts, so that when pig hearts are transplanted into humans, rejection will be reduced.” Analysis by Professor Zhao Qiang.
Professor Zhao also said that pigs can reproduce quickly, so it is appropriate for doctors to choose pigs as a heterogeneic source of donors.
“Of course, the pinnacle of transplant technology development, in the case of heart transplantation, is to use the patient’s own cells to create an artificial, flesh-and-blood heart in a laboratory culture, such a heart is ethically, theoretically and technically perfect donor.” In terms of genomics and immunology technology, China is keeping up with the international frontier and making unremitting exploration.” Professor Zhao Qiang said.
Whether genetically modified organ transplantation is for the benefit of mankind or opens a “Pandora’s box” still needs to be discussed and improved in terms of ethics, laws and regulations. In order to prevent life from dying while waiting, humans have a longer history of “transforming” organs, and in general, there have been more failures, but that has not stopped scientists from opening new explorations in frustration.
The death of the world’s first pig heart transplant patient may have a certain impact on the implantable pacemaker market, but the specific impact needs to be considered according to the following aspects:
- The cause of patient death: If the patient’s death is related to the pig heart transplant operation itself, it may raise questions and concerns about the technology from the public, which in turn affects the market demand for implantable pacemakers. If the patient’s death is not related to the pig heart transplant, the impact on the market may be smaller.
- Demand for implantable pacemakers: Implantable pacemakers are a common treatment for arrhythmias, and patient demand is related to the degree of acceptance of pig heart transplant surgery. If public acceptance of pig heart transplants decreases, it could reduce the need for implantable pacemakers.
- Implantable pacemaker market competition: There are already several competitors in the implantable pacemaker market, including major medical device manufacturers and biotechnology companies. If the pig heart transplant technology becomes widely used, it could increase the competitive pressure on these competitors.
- The development of future technology: With the continuous progress of science and technology, there may be more options for implantable pacemaker technology in the future, such as products based on artificial intelligence or nanotechnology. If these new technologies are widely used, they may have an impact on the existing market landscape.
In general, the impact of the death of pig heart transplant patients on the implantable pacemaker market needs to be comprehensively considered in light of specific circumstances. But in any case, medical device manufacturers and related enterprises should pay close attention to future market dynamics and technological developments, and do a good job in response.
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