Cardioprotective Flush, Without Reanimation, Safe and Effective in DCD Transplant

A new method of recovering hearts for transplantation from a broad group of deceased donors after circulatory death (DCD) is safe and efficacious, according to results from a single, high-volume transplant center. With this novel method—known as rapid recovery with extended ultraoxygenated preservation (REUP)—donor hearts are recovered without reanimation inside the donor’s body and without the assistance of ex situ machine perfusion.

Aaron Williams, MD (Vanderbilt University School of Medicine, Nashville, TN), who led the JAMA-published study, said REUP, pioneered at his center, involves a modified flush circuit that resuscitates the heart and protects it sufficiently so that it can be transported and transplanted.

“It really goes against the historic dogma that we’ve had in DCD heart transplantation—that has been the need to always reanimate or to look at the heart to see if it looks good or if it’s going to function well after someone’s passed away,” he told TCTMD. “The first two heart transplants in the history of heart transplant were reanimated, and ever since this time people have been restarting the heart, whether it’s in the donor or on a machine. We’re not restarting the heart. We are not reanimating it. It really just goes to show that what we’ve done for the last 50 or 60 years, you don’t need to do.”

Maryjane Farr, MD (UT Southwestern Medical Center, Dallas, TX), said the REUP technique developed at Vanderbilt University is a demonstration of the type of innovation that can occur at a high-volume center with dedicated time and resources to address the most important problem of transplant: increasing the donor pool.

“How can we do that safely, more economically, and how far can we do distance wise?” she commented to TCTMD. “What can we do to push the field?” While industry has been an important partner in improving care in donation and recovery, said Farr, “to really move the needle, [there’s a need to] focus and develop program capacity to do the type of work that they did.” 

In the US, according to the United Network for Organ Sharing (UNOS), DCD was used for 43% of all deceased donors in 2024. Only a minority of heart transplants occur following DCD, although the percentage is growing. There is increasing pressure from the US government to increase transplant volumes, and REUP represents a strategy that all centers can use, Farr said.

“It’s a little more like [donation after brain death] transplant where it’s standard organ procurement, flushing, and then cold storage and travel,” said Farr.

Pushing Ischemic Times Outward

The thoracoabdominal normothermic regional perfusion (TA-NRP) technique has been increasingly used as a way to decrease the ischemic insult that occurs between the stoppage of life-sustaining treatment and the confirmation of circulatory death. It involves restoring partial circulation in the donor’s body after circulatory death is declared, but some have raised concerns about whether it violates the “dead donor rule.” The worry, and it’s unproven, is that reanimation might result in brain or spinal cord reperfusion. There’s a moratorium on TA-NRP in several countries and in many parts of the US. 

That moratorium, said Williams, results in lost opportunities for those in need of a transplant.  

With direct procurement and perfusion (DPP), on the other hand, the heart is reanimated on an extracorporeal perfusion machine and assessed. While there are no ethical challenges with DPP, it’s technically challenging and requires significant personnel and planning. DPP costs about $100,000 per transplant and only organs of a certain size can be placed on the machine, said Williams.

“There’s high discard rates with this platform, too,” he said, noting that around 10% of hearts aren’t used after DPP. 

REUP is dramatically less expensive than DPP using commercial ex situ platforms—it costs around $2,000 per transplant—and eliminates the ethical challenges associated with TA-NRP, said Williams.

We’re not restarting the heart. We are not reanimating it. Aaron Williams

The REUP technique involves the use of an oxygenated perfusate, which consists of blood, del Nido cardioplegia solution, and other cardioprotective additives including valproic acid, administered as an extended flush over 10 to 12 minutes. Williams and his colleagues previously published outcomes of three early cases in the New England Journal of Medicine in 2025. 

In this series, 24 REUP-recovered hearts (83% male) following DCD were transplanted between November 2024 and July 2025. There were zero hearts discarded. The mean donor age was 32 years, with nine donors older than 40 years. The median time from the withdrawal of life support to flush was 28 minutes, while the time from the declaration of donor death to flush was 9 minutes. The median total ischemic time was 258 minutes, with a maximum total ischemic time of 8 hours.

Among recipients, 30-day survival was 95.8%. There was a single case of primary graft dysfunction and one case of secondary graft dysfunction. On day 7, all patients had a left ventricular ejection fraction > 55%.  

Implications of REUP

To TCTMD, Williams said their initial cases involved lower-risk donors with shorter ischemic times. Historically, in transplant, doctors aim to keep the total ischemic time under 4 hours.

“In our first series, those are the patients that we tended to focus on using this technique,” he said. “Once we figured out this technique works, we then tried to push the limit. We wanted to try to use it in older donors, which are higher risk. Older hearts don’t work as well as younger hearts. Not a lot of people feel comfortable pushing the ischemic time above 4 hours. We thought, we know this technique works, let’s push it. Let’s do 5, 6, 7 hours. Lo and behold, it works in all those scenarios with excellent outcomes.”

With REUP effective in older donors and longer total ischemic times, “we’re really talking about how we can get more people transplanted,” said Williams. “You may consider taking an older donor or some organ that’s farther away.” Regarding the single case of clinically significant graft dysfunction, the rate is significantly better than with the other recovery methods where rates range from 12% to 16%, he added.   

It’s team research that has immediate implementation [implications]. It will save lives. Maryjane Farr

Farr noted that the TransMedics Organ Care System, which is approved in the US for normothermic ex vivo perfusion, allows hearts to travel extended distances, all the way across the country, if necessary. The new study suggests that REUP may represent another way of doing things, although she still believes there will be a role for other procurement techniques.

“We’ve just added another platform to how this can be done,” said Farr. “It’s team research that has immediate implementation [implications]. It will save lives.”

In terms of what will become standard practice, time will tell, she said. “I think it’s too early to call [REUP] standard of care, because I think you need a little bit more data on 1-year survival and to compare that to other DCD [procurement and recovery] modalities, but it’s exciting work.”

Farr noted that one limitation of DCD, in general, is that the agonal period is limited to less than 30 minutes, but some donors do not pass away within that window. In the current series, the time from the agonal phase, which included several definitions based on oxygen saturation or systolic blood pressure, to flush ranged from 12.5 to 23 minutes.

“One benefit of maintaining the in vivo NRP platform is that if you’re worried that you went a little longer on the agonal time, you put the patient on [venoarterial extracorporeal membrane oxygenation] and reanimate the heart and do an echo to see if the heart still works. So, there’s a role, even with this advance, if you still want to see the heart beating.”   

Williams said it may take some time for other transplant surgeons to get on board considering that reanimating the heart has been the norm for decades. He believes, however, that the recovery technique is superior, noting that there is a single ischemic period with REUP as opposed to two ischemic periods with DPP and TA-NRP.

“I just think we need to keep having conversations about it,” he said. “The interesting thing is that we really formulated this technique out of the scenario that you can’t use NRP at certain places and [there’s a] cost associated with the perfusion machines. What’s amazing is there’s so many countries worldwide where NRP is not allowed or they don’t have access to the machines. This really is an answer for countries that can’t use the other two platforms.”