US doctors have reported the first experiences of heart transplant in three infants after cardiocirculatory death, rather than brain death, in the donors [1]. Lead author Dr Mark M Boucek (Joe DiMaggio Children's Hospital, Hollywood, FL) told heartwire this was, to his knowledge, the first published account of heart transplant in children after donor cardiac death, although organs other than hearts are transplanted after cardiac death.
Boucek et al report their investigational findings in the August 14, 2007 issue of the New England Journal of Medicine; the transplants were conducted at Denver Children's Hospital, in Colorado. The paper is accompanied by three perspectives [2,3,4] and an editorial [5], as well as a round-table discussion on the New England Journal of Medicine website [6], all of which ponder the many scientific, medical, legal, and ethical questions arising as a result of this work.
In one perspective [2], medical ethicist Dr Robert M Veatch (Georgetown University, Washington DC) says: "The results appear to open the door to heart transplantation after cardiac death."
And in the editorial [5], New England Journal of Medicine editors Drs Gregory D Curfman, Stephen Morrissey, and Jeffrey M Drazen say that despite the many controversial and differing opinions of the perspective authors and the ensuing debate–which they welcome–"one conclusion is clear. As a result of their investigational protocol, three babies are now alive; had the procedures not been performed, it is virtually certain that all six babies would be dead."
Heart Transplant After Cardiac Death Feasible, Especially in Kids
The practice of donating organs after cardiac death, rather than brain death, has gained acceptance in recent years, but only for organs other than the heart. There has been one report of a successful heart transplantation in an adult that involved a donor who died from cardiocirculatory causes, but concerns about the vulnerability of the heart to ischemic injury has limited further cardiac transplantation in adults from donors who have died from cardiac causes, Boucek et al explain.
But in children, heart transplant has been performed after prolonged ischemic injury in a donor, and the results were similar to those for donors without ischemic cardiac injury, they note. And the need for more pediatric donors is pressing, Boucek stresses.
"There are a significant number of kids who have congenital heart disease or develop disease of the heart muscle that prevent them from surviving, and their only chance is a heart transplant," he explains. And "the worst age for donation is in those under one, not because there are not a large number of children who die at this age," but because doctors feel a little less comfortable with declaring even brain death in such infants, he says, "so many of these children are not offered the option."
However, the parents of dying children are amenable to organ donation, he says, stressing the positive feelings that arise for the donor's family from giving the potential for life to another child.
Three Children Still Alive Three Years Later
When kidneys, lungs, livers, and other organs are transplanted after cardiac death, there are a number of differing opinions as to the length of asystole required before pronouncement of death, with times ranging from two to five minutes routinely used. But autoresuscitation of the heart has never occurred any later than 60 seconds after asystole, so this two- to five-minute period is a somewhat arbitrary concept, Boucek explained to heartwire.
And when the discussion moves from transplanting other organs to transplanting the heart, this time period is vital, he notes, because "the heart is the most vulnerable organ, and it needs to work at its optimum right after transplantation." The longer the period of time following asystole that is required before pronouncement of death, the more likely the heart to be transplanted will become damaged, jeopardizing the recipient.
Hence, in their protocol, Boucek et al started with a period of three minutes after asystole for the first transplant they performed, but thereafter "the feeling from the entire team was that we should shorten this, as we may have jeopardized the recipient." So, following extensive discussions including the hospital ethics committee and the data and safety monitoring board, they adopted a period of 75 seconds for the next two transplants.
"The outcomes after transplantation of hearts from donors who died from cardiac causes were similar to those associated with traditional organ donation," Boucek and colleagues note in their paper. "All three recipients survived despite being at high risk for death," and the six-month survival was 100%, compared with 84% for 17 control infants who received transplants procured through standard organ donation. And the three children are still alive three and a half years later, they note.
Distant Sharing of Hearts After Cardiac Death Would Have Great Impact
The legal and ethical issues surrounding this investigation that are debated in the perspectives and editorials are welcomed by Boucek, who told heartwire, "Discussion is healthy. There are a number of angles that are taken that are relatively extreme, and that's excellent, as the discussion should be full and uninhibited, and these are rational people with differing opinions. The whole thing should be done as transparently as possible. My hope is that this leads to more opportunities for transplantation."
He added that there is no reason why the protocol developed by his team, with perhaps certain adjustments to take into account local conditions, could not be performed anywhere in the world.
The one great limitation of this procedure, said Boucek, "is that you have to have a donor and a recipient at about the same time." If, however, the concept of heart transplantation after cardiac death could become mainstream and a donor heart procured following cardiac death could be flown anywhere within reason–as is the case currently for hearts donated after brain death–"this would have a huge impact," he stressed.
"For pediatric heart donation and transplantation involving patients who die from cardiocirculatory causes to become a more frequent option for end-of-life care and to affect significantly the nationwide risk of dying while waiting, the concept of distant sharing of donated organs from these donors should be considered," he and his colleagues conclude.
Boucek MM, Mashburn C, Dunn SM, et al. Pediatric heart transplant after declaration of cardiocirculatory death. New Engl J Med 2008; 359:709-714.
Veatch RM. Donating hearts after cardiac death–reversing the irreversible. New Engl J Med 2008; 359:672-673.
Truog RD and Miller FD. The dead donor rule and organ transplantation. New Engl J Med 2008; 359:674-675.
Bernat JL. The boundaries of organ donation after circulatory death. New Engl J Med 2008; 359:669-671.
Curfman GD, Morrissey S, and Drazen JM. Cardiac transplantation in infants. New Engl J Med 2008; 359:749-750.
Perspective roundtable. New Engl J Med. Available at: http://media.nejm.org/Data/DataSupplements/NEJMp0804161/664/ds.aspx?DSID=664.
Reviewed by Ramaz Mitaishvili, MD
