Science often raises large questions. The extraordinary surgery David Bennett, a Maryland resident underwent on the 7th of January when he received a transplant from a pig with a genetically engineered heart was not an exception.
The 57-year-old with end-stage heart failure was repeatedly rejected for a standard transplant and was considered a poor candidate for an ventricular assist device. His new heart is now running well and is accepted by his immune system. Bennett and his doctors at the University of Maryland performed the procedure. The world was a new place with many unknowns.
“I believe that even few years ago there was a belief that transplanting the heart and other organs was a from the reality of today. It seems that it’s moving very quickly,” Larry A. Allen (MD, MHS), University of Colorado School of Medicine Aurora told theheart.org – Medscape Cardiology.
Demand for donor hearts exceeds supply, and despite the advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations for them in terms of clotting, stroke, and infection. We’ve observed that the use of those devices plateau,” Allen said. “So, the idea of a non-human source of organs seems exciting and very important in the event that it can be made to work.”
Obviously potentially paradigm shift, but still a huge number of issues around immune tolerance and xeno-infection to be understood. Challenge for the field is how to develop evidence around such a novel approach
— Michael Felker (@DukeHFDoc) January 11, 2022
“I am thankful to the University of Maryland surgeons for their brave clinical work and amazing scientific innovation. However, it’s always in implementation that we must wait for the right time,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview.Heart xenotransplantation is an old idea that “has never been successful before,” he said. The the standard heart transplantation has set a high standard, with a 1-year survival of around 90% and a low 1-year risk for rejection. It isn’t known whether the new procedure can be able to meet the standards. There are other potential complications such as chronic rejection and cancers caused by long-term immune suppression. These are “major issues that require more time and careful monitoring.”
“Still a Nascent Technology”
“This is an exciting and brave step forward in the field of heart transplantation,” said Mandeep R. Viela, MD, Brigham and Woman’s Hospital Boston. However, “there are many difficulties there.”
Fascinating! Not to downplay the importance – but for me one of the most interesting parts was the flurry of messages I rec'd from folks outside of medicine. I wish the same excitement could be generated for GDMT w its applicability to more people @gcfmd @AndrewJSauer @dranulala
— Robert Mentz, MD (@robmentz) January 11, 2022
Mehra explained that the procedure’s 10 gene changes were designed to prevent acute rejection and the excessive expansion of the heart following transplantation and make the organ less immune-friendly. Even if these objectives are achieved, could the same changes may hinder the heart’s adaptation to human physiology, like during ambulation or stress?
That kind of adaptation may become important. For example, Mehra observed, normally the pig’s heart “provides flow through a four-footed structure and the temperature of pigs is significantly higher than humans by several degrees, so it is operating in a comparatively cold environment.”
Transplantation remains the gold standard for patients suffering from advanced heart failure, despite advances in medical and device therapy, Allen agreed. Allen said that if we can create pig hearts that can serve as the organ and manage rejection with genetic editing and targeted immune suppression and ad hoc immune suppression, then we could see this very quickly replacing a lot what we do in advanced heart failure and transplantation.
Absolutely, it would be a major advance when the gene editing procedure is successful in improving the heart’s immunologic compatibility, Yancy noted. But can we utilize our knowledge of genomics to make the best selections for gene deletions as well as insertions? “We must be aware that this technology is still in its infancy and that there may be consequences we didn’t expect.”
A true watershed moment in the world of ❤️ #Transplant. Xenotransplantation is the next stage of evolution for organ transplantation and will save the lives of thousands. @HFSA@ISHLT
First, Man Receives a Heart From a Genetically Altered Pig https://t.co/rItJ5AcBA3 pic.twitter.com/pFoo7MEr28— Ali Nsair, MD (@AliNsairMD) January 10, 2022
For instance, he stated that xenotransplantation as well as gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men as well as people of different races and ethnicities.
“There could be some differences based on ancestry, based on gender, or aging, that will influence the way in which these engineered donor hearts are viewed clinically,” Yancy said.
He also pointed out that the potential negative impact of xenotransplantation on health equity should be considered. “Almost certainly , it will be a very costly technology that will be utilized only in a very few population.” “We require a wide-angle lens to take into account all possible implications.”
“This Field Needs to Evolve”
Mehra also outlined the possibility of cost if it become a standard. Perhaps that could spur dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”
It might also teach the field to take more advantage of the numerous donated hearts that are considered to be suboptimal. “The general usage rate for offered organs is about 1/3,” despite opportunities to expand the use of organs that are “less than perfect,” Mehra said. “I believe that the field will develop by focusing the community on reduced discards of current available heart organs, but not necessarily grow because of the availability of “xeno-organs”.”
An amazing first and opportunity for our patients, but are we truly ready: infection,rejection,other options?
How does one do the first with appropriate learning ?@MRMehraMD @DukeHFDoc @robmentz @HeartBobH @califf001 https://t.co/pEKDggugVK— Christopher O'Connor (@coconnormd) January 11, 2022
“This field must evolve because we are currently transferring patients at the moment. However, in my opinion the ultimate goal is to have such an knowledge of the biology of left ventricular dysfunction that transplantation is a rare event,” Yancy proposed.
“I don’t believe that heart transplantation in itself is the ultimate goal. I believe that avoiding transplantation is the real end game,” he said. This might be controversial but I don’t think that we’ll ever have enough animals to transplant. My vision for the future is that heart transplantation becomes obsolete.”
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