Fewer Kids Now Die While Awaiting Heart Transplant, but There’s Room for Improvement

Mortality has substantially dropped over the past two decades for children awaiting a heart transplant, but still one in eight die while on the wait list, according to an analysis of US data.

Researchers argue that a new allocation system based on a multimodal score might be better than the current three-tier system, last updated by the United Network for Organ Sharing (UNOS) in 2016.

Similar calls have been made to change allocation of adult heart transplants, which evolved from a three-tier to a six-tier system, also in 2016. The pediatric protocol is similar to what’s used for adults, but involves different cutoffs for various measures (eg, creatinine) and accounts for children having fewer treatment options.

“The biggest issue is that kids who are wait-listed for a heart transplant in the United States continue to face amongst the highest wait-list mortality of any organ, and we're always looking for ways to try to improve upon that,” senior author Christopher Almond, MD, MPH (Stanford University School of Medicine, Palo Alto, CA), told TCTMD.

“We had somewhat thought that the work that was being done to improve the heart allocation system in 2006 and 2016 may have been helping. And I think it did in some ways,” he explained. “There are probably some subgroups that have benefited and others that may not, but on balance, it was a little bit difficult to find evidence that it made a major difference in mortality.”

Speaking with TCTMD, William F. Parker, MD, PhD (University of Chicago, IL), said he was not surprised to see pediatric data mirror that of what has been seen among adults.

“I was encouraged to see that the overall survival on the wait list or the rate of death without a transplant has declined significantly over time, but clearly their findings show that there's a lot more work that needs to be done on the actual prioritization of children on the wait list,” said Parker, who did not take part in the current study. “The allocation system rules could be improved to prevent even more deaths.”

Mortality Down by Nearly 40%

For the study, published in the August 13, 2024, issue of the Journal of the American College of Cardiology, Alyssa Power, MD (Stanford University School of Medicine), Almond, and colleagues looked at data from the Organ Procurement and Transplantation Network (OPTN) on 12,408 children listed for heart transplant between 1999 and 2023. They stratified the patients into three groups based on when UNOS implemented allocation changes: 1999-2006, 2006-2016, 2016-2023.

Wait-list mortality significantly decreased by a relative 38% over the three study eras from 21% to 17% to 13% (P < 0.01 for trend), with an overall mortality of 16% observed. The researchers found that children listed for transplant in the final era were less sick than those listed in the first, with less pretransplant use of extracorporeal membrane oxygenation (ECMO; 6% vs 12%), ventilator use (16% vs 27%), and dialysis (2% vs 3%; P < 0.01 for all). There was a greater use of ventricular assist devices (VADs; 17% vs 4%), and VAD mortality also decreased (10% vs 19%; P < 0.01 for both).

Additionally, mortality among nonwhite candidates went down from 24% to 14% and from 26% to 13% among children with blood group O, respectively, from the first to last era studied. Specifically for infants with type O, the death rate went down from 35% to 22%. At the same time, ABO-incompatible listings increased from 5% to 32% (P < 0.01 for all comparisons).

On multivariable analysis, the 2016 allocation changes were not associated with lower wait-list mortality, but VAD use, ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were tied to better survival.

“The current system we have to risk stratify patients doesn't risk stratify them very effectively,” Almond said. “A patient who's assigned tier 1 status maybe on average has higher risk than patients in tier 2 and then tier 3. But there the averages oftentimes don't describe most of the people. . . . Ultimately, I think the failure of risk stratification is because we aren't using enough data to risk stratify individuals.”

We aren't using enough data to risk stratify individuals. Christopher Almond

Instead, Almond said he’d rather see a system take patients’ individual characteristics and denote a continuous distribution or risk probability where they can be sequenced more according to their specific risk. Additionally, he’d like to see better measurement of factors like malnutrition.

Almond stressed that those who were invested in making the previous changes to the allocation system did so from a good place. “The intentions of people doing this are wonderful,” he said. “It just turns out that it's a really difficult task, and it's clear we can do better than what we're currently doing, but the devil's in the details.”

The good news from these findings is that the pediatric heart transplant community has pinpointed some things that are in fact leading to better wait-list survival, Almond added. “One of those is pediatric heart pumps; we're getting better at managing them,” he said. “There's a huge problem that companies aren't making pediatric pumps because there's so few kids that can benefit from them that it's not profitable for them. So, we're dealing with very old-fashioned pumps, but we're getting better at using those old-fashioned pumps and survival's getting better; we're supporting kids for longer.”

Advances that allow infants to receive transplants not limited by blood type—something that can only be done before the child turns 1 and develops antibodies—have led to better survival. Lastly, physicians for getting better at knowing when not to list a too-sick patient as eligible and taking steps toward narrowing the racial gaps over the years, he added.

What Is the Goal of Transplant?

“One of the main objectives of allocating scarce organs is to maximize or increase the benefits from the transplant, which means increasing survival benefit from transplantation,” Parker said. That means getting hearts to the patients who need them before they die and ensuring good survival after their transplant, he said, while simultaneously being mindful of ethics.

In an accompanying editorial, David L. S. Morales, MD, and Benjamin S. Mantell, MD, PhD (both from Cincinnati Children’s Hospital Medical Center, OH), agree that “although the intent of the policy changes in 2016 may have been to prioritize the patients with the highest wait-list mortality, the data presented by Power et al demonstrate that the policy change missed the mark in aligning medical urgency with listing status.”

They ask the question: “Should getting to transplant be the ultimate goal?”

Morales and Mantell, as well as Parker, agree that an ideal allocation system would be based on a continuous score rather than a three-status system. Moreover, the editorialists say this system should “integrate not only wait-list survival but also posttransplant survival, system efficiency, and equitable access to organs.”

Although this dream, potentially aided by artificial intelligence, may not become reality for several more years, the editorialists suggest a stopgap: “a rank-order continuous listing allocation system using multiple patient- and donor-specific factors to best determine which donor/recipient match results in maximized overall survival (both pre- and posttransplantation survival).”

Parker said he would like to see a pediatric-specific score created similar to the US-Candidate Risk Score for adults that his team published in JAMA earlier this year.

“That score, once developed, should be considered for implementation in continuous distribution for heart allocation, simulated and compared to the status quo, and see how many additional lives could be saved with a more accurate way of rank ordering children on the wait list,” he said. “Because ultimately that's the goal here, right? We want to give these hearts out in such a fashion to prevent children from dying, and the current system . . . has the rank ordering very mixed up.”