A 'Game Changer' for Heart Transplant?

Recorded March 4, 2023. This transcript has been edited for clarity.

Ileana L. Piña, MD, MPH: Hello. This is Ileana Piña. I'm at Thomas Jefferson University, and this is my blog.

I am thrilled today to have one of my good friends here with me, Dr Adam DeVore, who's the director of transplant at Duke University. There's been conversation about heart donations, and as most of you know, the hearts are not sitting on the shelf.

When our patients are sick, we really struggle — sometimes for months and maybe even years — to get a heart that is suitable for them, that is the right match, that has the right everything. Hence, many of these patients will die and others will need some kind of circulatory support.

Adam, you have presented on donation after circulatory death (DCD). Define that for us.

Adam D. DeVore, MD, MHS: In the field of heart transplant, DCD or donation after circulatory death is really a game changer. For decades now, we've been doing heart transplants from donors who die or have been declared brain dead.

There's a whole population of potential donors who have very similar neurologic injuries — they're just not technically declared brain dead — whose organs the family would like to donate. We didn't have a way before.

We and many other centers around the world have been working on trying to figure out a way to be able to use those hearts to transplant those people in need, as you mentioned.

Timing of Death Declaration and Recovery

Piña: What's the timing of, let's say, the true death and the recovery of the organ?

DeVore: This has evolved quite a bit. We were lucky at Duke to be the first center in the United States to do a DCD heart transplant in an adult in 2019. It's changed really quickly.

Piña: Has it been that long? My goodness.

DeVore: We started in December 2019, but it's changed so much in just a couple of years. We've learned that different hospitals initially had different protocols, and I think we're getting more and more aligned about what that looks like, what donation looks like.

Protocol Varies By Donating Hospital

Piña: What's your protocol like?

DeVore: In general, we're reliant on the donating hospital, but the hospital will withdraw care. Often, the family will be present.

Piña: Does your organ procurement agency help you?

DeVore: They do. We have a team, and then there is a service now that can also help with this through TransMedics.

Piña: They give you a call, and they let you know that there's a potential donor?

DeVore: That's right.

Piña: Does one of you go to that sister hospital to be present?

DeVore: We either send our surgeons or we use the National Service. One thing that's important to remember is we also tell our recipients that we've identified an organ, but not all of them will be able to be used. It really matters in the way the donor passes away, which is a little different than brain-dead donation.

Piña: And the status of that heart.

DeVore: That's exactly right, because that's something outside of our control, and we're never quite sure.

Piña: Do you cath them?

DeVore: Sometimes, we do. Often, because they haven't been declared brain dead, that's not allowed by the donating hospital.

Piña: The history becomes important, too, of that patient.

DeVore: The history, age, everything that's happened. We have done a cath on a heart that was outside the body in one of the ex vivo machines, but it doesn't provide the greatest pictures. We've also advocated for coronary CTAs that we've done in potential donors.

Piña: That might be a way to get around having to cath.

DeVore: That's right. We can still learn about the heart. There are two mechanisms. The family would withdraw care. Somebody affiliated with the hospital would declare that the donor has died. There's usually a standoff period. That is a little variable, but it's around 5 minutes.

Piña: They get declared.

DeVore: They're declared deceased.

Piña: That's when the clock begins.

Normothermic Regional Perfusion vs Direct Procurement

DeVore: Then there is a 5-minute standoff period before donation. This is the part where I think we still have much to learn.

There are then two ways where that heart could be resuscitated or revived, either outside the body on the organ care system. Or it could remain in the body through normothermic regional perfusion, or they'll go on cardiopulmonary bypass and re-perfuse the heart.

Piña: In the room?

DeVore: In the room, and then look at the heart and try to evaluate it before donation. The rest of that donation looks just like every other brain-dead donation.

Piña: How does the family handle this? I would think it may be tough for some families.

DeVore: I remember when we were first starting this, I was thinking of how we would explain this to potential recipients and what would this look like. It turns out that something terrible has happened, and families that want to donate organs are relatively enthusiastic and less focused on the details.

Piña: Maybe they've already gone through their grieving process.

DeVore: The same thing on the recipient side. As we talk to patients, they're in need. As you said, they're fearing death. The exact mechanism of the donation becomes a little less particular to them.

Piña: How did you set up the program at Duke?

DeVore: Well, it wasn't me. It was a large amount of work over the years. Jacob Schroder, our head of transplant surgery, was a big advocate for this for a long time.

Piña: You have a good surgical partner.

DeVore: We do. We started thinking about this all the way back in 2016, when we first started using the ex vivo organ care system from TransMedics. As soon as we started using that, he was familiar that they had done this in Europe and said that we really need to bring this to the US.

I think you have to credit him and a bunch of other surgical investigators who really pushed for a randomized trial. They said, look, we know this is feasible. We've seen it done for other organs. We've seen this in Europe.

Piña: You need the science.

DeVore: You need a randomized trial to show that it's safe for patients. Otherwise, how are we going to talk to patients about this?

Piña: Did you do that?

DeVore: We did. The OCS DCD Heart Trial is one of the very few randomized trials that happened in the heart transplant space, as you know.

Piña: It's really amazing that you were able to do that. How many patients?

DeVore: There were 180 patients randomized, with 90 in each arm.

Piña: Were all of them at Duke?

DeVore: No, not all were at Duke. This was around the United States. Duke did happen to be the highest enroller, but there were others. The patients were randomized right at the time they went on the transplant list to a strategy. Did they have access to DCD hearts, or did they not have access to DCD hearts? If you think about that for a minute, it's really complicated. You can't randomize at the time of acceptance. We had to randomize upfront.

It was run as a noninferiority trial, and there was no difference in terms of outcomes. If anything — we looked at 6-month outcomes of the trial — it favored the DCD arm, which is really encouraging and really reinforces that this is a strategy we can do to expand the donor pool and offer transplant to more patients.

Piña: How many have you done at Duke?

DeVore: I've lost track. We recently did our 100th transplant. We've done quite a few.

Piña: Wow, that's a lot. Is that from 2019 to now?

DeVore: That's correct. Yes, until now.

Learning Curve and Delayed Graft Function

Piña: What would you tell other programs that would want to do this?

DeVore: A couple of things. One, there is a bit of a learning curve, and we had to really think through which patients would be the first ones for us to do this with. For those patients in the hospital who are critically ill, this was a really important strategy to try to get them transplanted faster before complications happened on mechanical support. Our outcomes have been great. There is definitely something we call delayed graft function as opposed to traditional primary graft dysfunction (PGD).

Piña: It takes a little while.

DeVore: If you think about it, it's gone through more of a stress than a heart that would for brain-dead donation.

Piña: Do you cross-match the plasma reactive antibodies (PRAs)?

DeVore: We have basically the same approach. No difference.

Piña: You have to know the PRAs of the donor heart as well.

DeVore: Yes.

Piña: When you say it's sluggish, how sluggish?

DeVore: It's relatively common for people to have to come out on a balloon pump or ECMO support, but we've published on this. It's actually a shorter amount of time. It's not quite the same as we've seen with traditional PGD, where the heart struggles for 24-48 hours. It's really a couple of hours. As you get used to that, you plan for it and are able to support the patient, and they do fine. We started with sicker recipients, but we were able to then back up and offer [DCD transplant] to other patients.

Piña: What do you do with immunosuppression? Do you give it early?

DeVore: No difference. We haven't observed earlier rejection. That hasn't been studied in a very rigorous fashion.

Piña: You do your tacrolimus and your CellCept and everything just like you would normally?

DeVore: Everything's the same. We don't treat them any different. We haven't really observed any differences.

When we first started, we were doing MRIs on patients before they went home to see if there was any early dysfunction that we should be worried about, since they did go through that extra ischemic period. We didn't see any differences.

Piña: How long is your longest survivor now?

DeVore: The first one from December 2019 is still doing well.

Piña: Amazing. This is so welcome because we've been through accepting hepatitis C hearts. Then we asked, should we accept previous COVID-19 patients? There are so many of these. How horrible for those families, but it almost sounds like a little bit of a redemption to be able to donate.

DeVore: As you know, this goes on and impacts many lives.

Piña: Well, I hope you get this published soon, and I'll be excited to see if it comes to Jefferson.

DeVore: That would be great. We'd love to work with you guys and your program.

Piña: Thanks for joining me.

To our audience, this is a very exciting and different approach to getting some of our patients the organs that they so need. In your own communities, encourage donation and encourage individuals to become organ donors, because that is equally important.

Thank you for joining me today. This is Ileana Piña signing off.

Ileana L. Piña, MD, MPH, is a heart failure and cardiac transplantation expert. She serves as an advisor/consultant to the FDA's Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982. Originally from Havana, Cuba, she is passionate about enrolling more women and minorities in clinical trials. She also enjoys cooking and taking spin classes.

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