Efforts underway to shorten highest mortality wait in transplant medicine
November 17, 2010
Boston, Mass. - Donor hearts from infants who died from sudden infant death syndrome (SIDS) appear to be as safe for the transplant recipients as hearts from other infant donors, report researchers at Children's Hospital Boston and their colleagues. The findings may help alleviate a shortage that puts infants listed for heart transplants at greater risk of dying on the wait-list than any other age group or category of organ recipient.
In the last decade, hearts from infants who died of SIDS have increased to about 10 percent of all infant heart transplants, but uncertainty about the safety of SIDS hearts has lingered.
"The outcomes are essentially no different from transplanting hearts from kids who died of other diseases," says Children's transplant cardiologist Christopher Almond MD, MPH, senior author of the study in the November 2010 Journal of Heart and Lung Transplantation. Boston Children's cardiology transplant team conducts about 15 to 20 heart transplants a year and typically has about 20 to 25 children on the waiting list.
In their study, Almond and his colleagues analyzed the results of 1,033 infants younger than 12 months who underwent heart transplants between 1994 and 2008 in the United States. Of the total, 66 infants (6.4 percent) received a heart from an infant who died of SIDS. Overall, the transplanted hearts survived in their recipients for 14 years, with 307 deaths and four re-transplants.
"It doesn't mean all SIDS hearts are acceptable for transplant," Almond said. "They must go through the same screening process as all potential donor hearts. But if all the tests look normal, a heart that comes from a child who died of SIDS may be a reasonable way to expand the pool of eligible donors." The findings may save the lives of dozens more infants every year.
Nearly two years ago, Almond and his colleagues found that infants and toddlers suffered a disproportionate share of the 533 deaths in the 3,098 children younger than 18 listed for heart transplants from 1999 to 2006. In response to the excessively high deaths on the waiting list for pediatric hearts, the United Network for Organ Sharing has convened a committee to review the heart allocation system in children. Almond is on the committee.
"The question is, can we utilize available donors in a way where the overall benefit to society and to children is maximized," T.P. Singh, a Children's transplant cardiologist and a co-author on the study said. "The idea is to minimize mortality both pre- and post-transplant."
Concern about the safety of SIDS hearts stems from scientific uncertainty about the precise mechanism of death and the potential that an unrecognized cardiac issue could also affect a heart transplant recipient. Evidence suggests that SIDS involves multiple minor events, including cardiorespiratory and neurological, whose chance convergence results in a tragic outcome, concluded Children's pathology researcherHannah Kinney, MD, and a colleague in a August 20, 2009, review article in the New England Journal of Medicine. Kinney and her group have reported several abnormalities related to the neurotransmitter serotonin in the lower brainstem of SIDS infants in regions that help control breathing, blood pressure, heart rate, and temperature.
"Only a small proportion of these SIDS infants can be expected to regain a spontaneous circulation with cardiopulmonary resuscitation to become a candidate for heart-beating organ donation," Almond and his colleagues noted in the paper. But, they added, "unpublished 2004 data from the Pediatric Health Information System database suggests that more than 100 infants with a final diagnosis of SIDS had sufficient circulatory function to be admitted to an inpatient pediatric bed before their eventual death."
The SIDS hearts selected as suitable in their study likely had normal-appearingelectrocardiograms and echocardiograms, while those with abnormal findings were likely rejected. That likelihood provides "real-world evidence" that carefully selected SIDS-donor hearts may have similar post-transplant survival, the researchers conclude.
Almond, Singh and their colleagues are tackling the issue from a number of other directions. Almond is the co-principal investigator of a national clinical trial of the Berlin Heart, a miniaturized mechanical circulatory support device to improve survival of infants and smaller children on the waiting list.
Earlier this year, the team reported that infants listed for hearts of incompatible blood types, known as "ABO-incompatible transplants," in the US had a meaningful reduction in waiting list time. The developing immune systems of infants younger than 6 months seem to accept the incompatible organs equally well. So far, the strategy tends to be used for the sickest infants, but could benefit many more immunologically eligible infants, the team concluded.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 392-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Boston Children's visit: Vector Blog.