Owen Monroe, the little one transplanted in the USA in 2022, is doing well. The study with positive results was published in Jama: the implanted heart valves integrated into the body and developed. Also used less immunosuppressive drugs
Little Owen Monroe celebrated his birthday with a double champion achievement: becoming the first newborn in the world to receive a partial heart transplant in September 2022 and, now, having spent another year of life during which the tissue used to repair his heart has grown alongside his development. The positive results of these first 13 months of life are evident, looking at the photos and videos taken by Nick and Tayler Monroe, his parents, after the transplant.
But they are also reported in a scientific guise in an article published on Jama by the team of Joseph W. Turek, first author of the study and head of pediatric cardiac surgery at Duke Health (Duke University School of Medicine, United States). The partial heart transplant procedure has been so far performed 13 times in four centers around the world, including nine at Duke Health. As heartbreaking as this was for our family, we knew from the start that Owen was in the best hands, she reiterated Nick Monroe. Our greatest hope is that Owen’s success story will change the way organ donation and transplants are handled not just for children with congenital heart disease, but for all patients.
Kathleen Fenton, pediatric cardiac surgeon and bioethicist at the US National Institutes of Health, defines the partial heart transplant performed at Duke Health as a pioneering intervention and a paradigm shift in neonatal cardiac surgery and pediatric heart transplants, in an editorial appearing in Artificial Organ. The new procedure has also caught the attention of Hollywood screenwriters, who included the story of little Owen in a recent episode of the television series Grey’s Anatomy.
Owen’s disease: a rare, congenital heart defect
The idea is very good – agrees Professor Lorenzo Galletti, head of Cardiac Surgery at the Bambino Ges hospital in Rome – because it fills a gap that exists precisely in certain very rare heart diseases: using the valves of hearts that otherwise would not be used because they do not have the perfect muscle. In this case, the child’s heart disease we are talking about is a truncus arteriosus (trunk arteriosus, a rare congenital heart defect in which from the heart, through a single valve defined as truncal, with only one large part artery instead of two, which are normally: pulmonary artery towards the lungs, aorta towards the rest of the organism, ed). But in reality the idea can also be used for other heart diseases.
What is partial heart transplant
Partial heart transplant a new approach to provide heart valve implants that grow with the baby: the part of the heart that contains only the outflow valveswhile I ventricles natives are spared. Partial heart transplants differ from homologous transplants (or homotransplants) from a cadaver because they are treated like heart transplants to maintain the viability of the valves. It allows partial heart transplants to grow just like the valves in full heart transplants.
What has been used up to now are valves of human origin which also come from hearts not used for transplantation, but treated in a certain way, that is cryopreserved at minus 180 degrees centigrade – explains Professor Galletti -. Cryopreservation allows the valves to be preserved for 5 years. However, the possibility of degeneration of these valves, which then fail to grow and calcify, greatly increases. The cryopreserved valves require frequent replacements and therefore the child must undergo new operations which increase mortality and morbidity over time.
The risk of rejection and immunosuppressive therapy
This publication proves that the technology works, the idea works and can be used to help other children, says Joseph W. Turek, first author of the study and chief of pediatric cardiac surgery at Duke, who performed the valve transplant. In transplantation, one of the major obstacles to overcome is the rejection of the organ which is recognized as an enemy by the immune system of those who receive it and are attacked. To limit the damage, immunosuppressive drugs are used, used to reduce the activity of the body’s defense system.
The study also revealed that This type of transplant requires about a quarter of the amount of immunosuppressant drugs needed compared to a full heart transplant, potentially sparing patients from harmful side effects that could worsen over decades. Compared to a whole heart transplant in which, if rejection occurs, cardiac function is depressed, the problem here is minor – explains Professor Galletti -. Because, if there is rejection, in the end the implanted valve becomes like a valve of those used traditionally, i.e. cryopreserved, which will undergo degeneration but does not have a direct negative effect on cardiac function.
Domino heart transplant
According to Joseph Turek, the new approach paves the way for domino heart transplantation, where a heart capable of saving two lives. During such a transplant, a patient who has healthy valves but needs a stronger heart muscle receives a complete heart transplant; the healthy valves are then donated to another patient awaiting surgery, thus creating a domino effect. It potentially doubles the number of hearts used, benefiting children with heart disease, Turek points out.
Of all the hearts donated, approximately half meet the criteria to be used for complete transplantation, but we believe there are an equal number of hearts that could be used for valves. “If you introduce donated hearts that have not been used into the supply chain and add valves from domino heart transplants, you can create substantial change,” Turek continues.
Regarding approaches to providing neonatal heart valve implants with the potential for growth, the path totissue engineering. This is a procedure that uses the 3D printing or the decellularization of organs. In practice, cells are combined with some support structures called in technical terms scaffold, i.e. scaffolds, necessary for cells to exist and function. In 3D printing, scaffolds are printed layer by layer and assembled based on a mathematical model. In the decellularization, instead, scaffolds are produced through the destruction of the cellular compartment of a human or animal tissue. However, this type of approach has so far failed to have important clinical applications.
Unfortunately a very difficult procedure – specifies Professor Galletti -. Ideally the perfect solution, because not only is a “human” valve created but also with the cells of those who need it. So at that point you really overcome the problem of rejection. Technology has not yet given us answers that can be translated into the clinic.
The partial heart transplant procedure has been performed 13 times at four centers worldwide, including nine at Duke, many of which were domino heart transplants. Turek convinced that bringing this innovation into one clinical trial it would be the next step to reach the volume of interventions necessary to significantly change the availability of hearts. This innovation adds a lot to the entire donation community, Turek said, because it allows more children to be treated while honoring the wishes of the altruistic donor parents who gave the ultimate gift. It allows them to offer hope to another child.
That of partial heart transplant a line of research also followed in Italy? Maybe from tomorrow it will become one – replies Professor Galletti -. The study just published will certainly make us reflect. The rationale of the study is based on rough bases that are simpler to implement. A paradigm is probably opening up. Then whether in five years we will have really implemented it, we will have to see.
Pediatric heart transplants in Italy
What is the picture of heart transplants on children in our country? In Italy they are performed approximately 25 pediatric heart transplants per year. More or less between 1/3 and half we do them to the Child Jesus – says Professor Galletti -. Then there is the whole world of artificial heart pediatric, where in reality technology is not helping us much because the pediatric artificial heart is not simply the miniaturization of an adult artificial heart. The problems are more complex, so much so that even the American trials on this technology have produced nothing, because the development of these technologies is very expensive and the group of potential recipients is very small. Furthermore, it is not like in adults, where the model is more or less unique. In pediatrics, there are different models depending on the child’s weight class (under 8 kg, between 8 and 20, between 20 and 30, between 30 and 40).
With regard to the valvesreplacement in pediatric age is another issue because, even if the technology of mechanical valves, which are used in adults, has allowed their miniaturization, there is the problem ofanticoagulation. And anticoagulation brings with it a number of accidents related to or thrombosis or the hemorrhage being evaluated approximately zero 5% per year. So if I transplant at sixty and life lasts 80 on average, I expose a person for twenty years. But if I intervene in the pediatric age, I expose that patient much more. Biological valves traditional ones, it is better not to use them because, as already mentioned, they degenerate and calcify very quickly. So the possibility opened up by the Duke Health study is to have valves with living tissue which can grow together with the transplanted child – even if not for the whole life, but let’s say for a phase of development which then allows perhaps to make a single replacement with an adult-sized valve -, already a potential improvement and not a small one , concludes the heart surgeon.
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January 5, 2024 (changed January 5, 2024 | 08:30)
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