Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And we have a panel for you today with two UAB Medicine specialists discussing Expanding the Donor Pool: the Rise of DCD Heart Transplantation and Advances in Organ Preservation. Joining me in this panel is Dr. Rajamiyer Venkateswaran, he's a cardiothoracic surgeon; and Dr. Jose Tallaj, he's the Medical Director of the Heart Transplant Program.

Doctors, thank you so much for joining us today. And Dr. Tallaj, I'd like to start with you. For listeners who may not be as familiar with DCD heart donation, tell us a little bit about what it is and how it differs from a traditional donation after brain death.

Dr. Jose Tallaj: Thank you for having us in the conversation. So, the way we traditionally think about heart transplantation or donation is donor who is brain dead. That means that something might have happened to the donor to the point that they have no brain activity. Legally, that person is not considered alive. So, brain dead is considered the typical donation that we do. However, the patient is brain dead, but the other organs are working, the heart, the kidneys, the liver, and that's the usual and traditional method of harvesting organs for transplantation.

The new one is these patients who are still alive, they still have brain activity, but whatever condition they may have, either a CNS event or having some other disease, the family has decided to withdraw support. So, they have made the decision that the person is not going to survive the current illness, so the family decides to withdraw.

So during the withdrawing process, the brain is still alive, has activity. So, what we have done and that took a lot of—I know Dr. Venkat is a master in that—is that we allow the patient to die in a controlled environment. So as soon as the patient's activity, cardiac activity stops, then we give them some time, make sure there's no recovery of organs or cardiac function. And then, we do the harvesting of the organ. So, we do it once the patient's circulation has subsided; therefore, the name of DCD.

So, it's a little bit different than what we consider that. There are certainly way more patients whose care is getting withdrawn for whatever reason that may be otherwise suitable candidates for donation. We are actually taking advantage of that now, and that is a way of increasing the donor pool since donation is kind of sparse and we have more patients waiting for transplant than organs available.

Melanie Cole, MS: Thank you for that. So Dr. Venkat, why has DCD become such an important area of focus in heart transplantation over the past several years? Is this lack of donor organs? Is this more need? Tell us why this is so important.

Dr. Rajamiyer Venkateswaran: Thank you again for having us. And as Dr. Tallaj mentioned earlier, the DCD is a concept where we were using only the brain-dead organ. Now, just to add a few points, prior to 1980s when the concept of brain death was not established by the academy of the all the colleges and the medical societies, all the donation happened as DCD because the only way the death was declared was the heart stopping.

So, it's almost that it's not something new. We are going back to how it was in the past. So, we are revisiting because some of those patients are not really brain dead, but they're not going to have a full survival or meaningful survival. So, the doctors decide to withdraw support, including all the life-sustaining treatments and the tube in the throat, and then the donor basically stops breathing and hypoxia leading to cardiac arrest, and the heart stops, the circulation stops, and the death is declared.

Now, why it is important? Because we are seeing more and more donation after circulatory death. That's because of the neurosurgical care is improved and the treatment for the road traffic accidents and also for the drug overdose or whatever it is, where with an improvement in the medical facilities and care, we are seeing more and more patients who probably would have become a brain dead in the past are probably turning into DCD donation.

And if that means if they are not brain dead, then if we don't start using DCD, these organs would go to waste, unless otherwise we are able to use them. What is happening in the Western Europe is that almost fifty percentage of the organ donors are turning as DCD donors. So in the past, it used to be 90% brain dead, 10% DCD.

But slow and steadily, the number of DCD donations increased to the extent that it's almost fifty percent of the activity in the Western Europe. So, that means if you don't use them, you're going to have less donor pool, so we have to find a way to use them. And that's when the Australian medical cardiologists are the ones who did a lot of research along with the people in Cambridge. And then, the first DCD heart transplant in the current era was performed in Sydney, followed by in Cambridge in England. And I was working in Manchester, and that was that fourth center in the world to start the heart transplant from the DCD donor. And that led to widespread acceptance worldwide. And now, DCD transplant almost is a thirty percentage of the activity in the US.

And in UAB, we have done almost thirty-five percentage of the current year's activities from the DCD. So, it is to increase the activity and also to make sure that we accept these organs otherwise would have gone wasted.

Dr. Jose Tallaj: So, the one that we haven't discussed, but one of the main issue is that in cardiology in general and CV surgery, we're getting better with everything else that we do. So if you have a heart attack, we have a better way of rescuing somebody in the cath lab, if you're having bad hypertension for many years. And so, patients are living longer with more diseases. So, a lot of the patients, I assume, and this is going to be true for the upcoming future, more patients will reach a point of having end-stage heart disease, certainly more so than 20 years ago where maybe your chances of dying from an MI in the cath lab was much higher than what it is now.

But then, what happens is over time, those patients will reach end-stage heart disease where nothing else could be done, meaning interventions or defibrillators, but they will definitely benefit from a heart transplant. So, the need for transplantation and advanced therapies for heart failure, I think, is going to continue to increase over time.

Melanie Cole, MS: This is a fascinating topic. So, Dr. Tallaj, I want to jump right to this question because I think that it's top of mind for everyone listening to this podcast is, what are some of the misconceptions or concerns about DCD hearts that you think clinicians should understand? And indeed, patients and their families as well as you're withdrawing other support, but there's still some possible brain activity. Are there some ethical concerns? Do patients have concerns? Do other clinicians have concerns about the hearts themselves and the transplant?

Dr. Jose Tallaj: Yeah, that's a great question. So, most of the limitations that we have these days has to do with ethical considerations. Interestingly, I don't think I've had a patient kind of refuse getting a transplant from a DCD donor. A lot of the ethical consideration comes from the medical community more than anything else. Remember that these patients that are DCD donors, the family has already decided to withdraw. So, it's not like they are like you and me walking around and doing well. These are patients who have a terminal disease that is going to lead to their withdrawal of care.

So, at that particular point, they are approached and then, "Hey, what about if we do it in a controlled environment and we can utilize the organs afterwards?" And actually, most families actually do agree with that, same as they do with the brain death donation. And the medical community has more of a harder understanding of the process whether the patient is alive and has brain activities when the organ is retrieved. But remember, we wait for the donor to actually cease circulation. So by all sense, that person has actually passed, has no circulation, the heart has stopped. And then, after a five-minute period or waiting period is when we start harvesting the organ. But my experience, and I don't know what yours is, Venkat, the ethical considerations are coming more from the physician side than actually the patients and families and even the donors' families' concerns.

Dr. Rajamiyer Venkateswaran: Absolutely. I think I agree with that. And this also to do with the way the heart is procured from these donors. There are two techniques currently available. One is called normothermic regional reperfusion, which is the thoracodominant perfusion, which means to restart the circulation on the dead patient in the operating room by putting them on a bypass machine. And as soon as the heart gets oxygenated blood, it'll start beating again.

So, the ethical point comes here is five minutes before the patient was alive, and we declared the patient dead because of the heart stopped. And then, another five minutes later, you are actually restarting the heart within their body. So, that's where the ethical issue comes in the regional perfusion.

There's other technique of taking the heart out is what's called the direct procurement, where the dead patient's brought to the operating room, quickly chest is opened, and the blood from their own blood is drained into a machine. And then, the heart is flushed with the cold solution with high potassium, and the heart's taken out and then reperfused in the machine. And then, it starts beating outside the body. It's called ex situ perfusion. So when it's perfused outside, then there is no ethical issue because you're not restarting the heart inside. So at the moment, there are certain countries, especially in the United Kingdom in England, the heart is not allowed to restart within the patient's body. So, everything has to be done outside. But in the US, there are some states, completely against restarting the heart in situ. That's where the ethical dilemma and worry comes from.

Dr. Jose Tallaj: Yeah. A lot of the time, it's actually hospital specific. So, each hospital has their own criteria as to what's considered a suitable retrieval process or harvesting process for DCDs. Some will allow the NRP to resuscitate the heart inside the body. Some will not and has to be done with direct procurement only.

Melanie Cole, MS: Well then, Dr. Venkat, what does current data tell us about the outcomes with DCD heart transplantation compared with traditional donor hearts, and how much has it contributed to increasing that number of heart transplants being performed nationally?

Dr. Rajamiyer Venkateswaran: When people started doing heart transplant from DCD donors, we chose low-risk heart recipients from the waiting list because we needed to understand how it's done, the outcomes are good. So, we didn't want to put it into a very high-risk sick recipient.

But as the experience improved, people started using it as any other brain-dead donor heart. So in the current climate, we are just using it for all status 1 and status 2 patients who are very sick, who are on machine support and multiple inotropes pre-transplant. And I must say, as per the International Society of Heart and Lung Transplant report, as well as from the UK's Cardiothoracic Transplant report, the 90 days and the one-year survival for the DCD heart transplant and also the five years heart transplant survival is no different to a brain-dead.

However, there is some increased risk of the needing temporary ECMO support after heart transplant from the DCD donor. That's because this heart that was perfused in that machine called heart in a box machine, they slightly become heavy and edematous and waterlogged. So, they develop dysfunction in the recipient, so they need to be supported on ECMO machine. We call it as primary graft dysfunction, but that is slightly higher than a brain-dead, but the results in the end are no different to a brain-dead donor, even one year, even up to five years.

So, the second question is, has this contributed to an increase in transplant activity? If you look at the UNOS, there is definitely a slight increase in the heart transplant number in the US. But that doesn't mean that we have solved the problem of the supply and demand issue because, as Dr. Tallaj mentioned, the waiting list still remains high. But at least we are continuing to maintain a equal number of heart transplant activity with slightly higher level because of the DCD utilization. If we hadn't, we would probably lose thirty percentage of the heart transplant numbers, and the numbers would be much lower. So, this is probably helping us to keep our activity with good outcomes.

Melanie Cole, MS: Well, thank you for that. And, Dr. Tallaj, what has the experience been like at UAB? How has this changed access to transplantation? And as Dr. Venkat just mentioned, for patients on the wait list, how is this affecting them?

Dr. Jose Tallaj: So, that's a great question. So when DCD started several years ago, just like Dr. Venkat mentioned, it was a way of getting patients who were lower risk transplanted, so status 3, 4, and, maybe even 5. Well, that's not the case anymore. As we know more and understand more how to manage these patients, how to manage these transplants and the early post-op management, we actually open up to everyone.

So because the allocation system is now nationalized, meaning that we may have a donor here, even in our own hospital, but we may not be primary, maybe primary may be elsewhere, so we go through a national and regional list. I guess we have taken the decision that certainly the DCD donors will be just like a regular donor. They go through the list as status 1 and status 2. We're approaching this year probably 30%, 40% of the transplants that we have done that are done are DCDs. There's a little bit of difference in how we manage them post-op or post-transplant just because this heart may take a little bit longer to recover, they may need some support early on, but the outcomes have been excellent.

And certainly, we consider a DCD donor as good as a regular brain-dead donor, and that's the way we present it to the patients and the patient's family.

Melanie Cole, MS: Dr. Venkat, I'd like you to speak a little bit about the perfusion systems. What information can transplant teams learn from the heart while it's on a perfusion device that they couldn't access before? And this has been one of the bigger advances, has been this ability to preserve and assess the donor's heart outside the body, and we're learning about that for kidneys as well. Tell us a little bit about how it works and what information you've been able to gain from it.

Dr. Rajamiyer Venkateswaran: Oh, that's a very highly complex subject. We are probably still learning as we do more and more. The currently available system either uses a normal temperature, which is 34 degrees, what was used, so it's called normothermic perfusion. There is a new machine which is currently going through a FDA trial. It's called hypothermic perfusion, which is a four-degree centigrade cold solution. So, it's called HOPE, H-O-P-E, which is hypothermic oxygenated perfusion machine. So, they are the two in the pipeline, but the currently utilized fully FDA-approved device is the normothermic perfusion, which is a company called TransMedics based in Boston. They are the ones who run it.

So, what we know is that when the heart is perfused, what we get it's a pulsatile pump, which pumps blood into the aorta. So, that means the coronary arteries that supply the heart gets the blood supply. And then, the coronary artery blood comes back to the right side through what's called as coronary sinus. Then, this gets pumped through the pulmonary arteries, and there is a cannula into the pulmonary artery, and then that blood goes back into a reservoir, gets oxygenated, pumped back. That's the principle of that machine. So, it's a sort of a small mini bypass circuit like, but perfuses the heart.

What we get is the information about how much is the blood is flowing, what is the pressure at which it's perfusing the aorta, which is called the aortic pressure. We also get how much is the blood into the coronary arteries, called coronary blood flow. We also get some saturations, and finally, we get lactate levels.

Now, lactic acid is primarily utilized by the heart when it works. So, what we measure is a lactic acid from the coronary artery side or from the aorta and from the coronary veins, which is the coronary sinus return, which comes out of the pulmonary artery. So, we measure the lactic acid at both. And what one would like to see is a arterial level is slightly higher and the venous is lower, which means the heart is eating lactate. And you should see a slowly reduction in the lactic levels as the heart's on organ care system for a few hours. Because these donors are anywhere in the region, like Dr. Tallaj mentioned. So, you could have an hour of all this in the donor hospital and then transported to the nearest airport and then flown to Birmingham. All these things could take three hours. So, the heart will be monitored on that. And what we see is all these parameters, and we would like to see a good perfusion, good coronary blood flow, and reducing lactate.

And again, there is not much published, and we are still learning from it. Because I have done this before when I was working in Manchester, and I understand some of these concepts, around forty percentage of the transplant centers in the US have not done a single DCD heart transplant because of this worry about understanding and how difficult it is to manage a heart on the TransMedics machine. So, people are very apprehensive, and that's why around fifty-five percentage of the transplant centers in the US have used DCD, and around 40% still haven't used a DCD donor for heart transplant.

Melanie Cole, MS: What an exciting time in both of your fields, and I'd love to give you each a chance for a final thought here. So, Dr. Tallaj, how have the technologies changed the way donor hearts are transported over long distances? You know, we've all heard about the coolers, seen it in the media, that sort of thing. And now with the perfusion systems and everything you've been discussing here today, what are some of the exciting technologies going on that can really help these transplants be more efficient and effective?

Dr. Jose Tallaj: I think we have several new devices, and then there are a few other ones that are under evaluation. All has to do with the temperature of the cooler, what solution we're using, whether they are beating or non-beating. I think the exciting issue, the exciting thing for patients is that we are getting better. We are getting better at preserving the heart, knowing the heart is good or bad. And I think that's what's led us to kind of embarking something like DCD, that it was a concept that we really didn't think about it several years ago, when we can actually try to resuscitate the heart before it is implanted.

So, that has led and will lead to certainly more transplants, hopefully get additional distance added to transplantation as opposed to have local go farther and farther away, and that will hopefully lead over time to an increased survival and outcome in transplant recipients.

Melanie Cole, MS: Yeah, that's very interesting. And what a fascinating discussion this is. Dr. Venkat, last word to you. If you're to look ahead, what innovations do you think will have the greatest impact on heart transplantation over the next five to 10 years? Give a little blueprint for research on the horizon.

Dr. Rajamiyer Venkateswaran: Do we really need the heart to be beating? Could it be just kept perfused at a lower pressure and with a little bit of oxygen so that we can avoid the heart becoming waterlogged edematous, as I mentioned before? So again, that's a huge research sort of concept.

And this is where that hypothermic oxygenated machine called HOPE, which is undergoing FDA trial at the moment. And they have used that machine in Australia and New Zealand, where the distance between Australia to New Zealand is so far, and the organs from Australia have been transported to New Zealand and been transplanted with over six to eight hours ischemia. And also, there are some case reports where an organ moved from Atlantic Island to almost to the city of Paris over a commercial flight.

So again, with all these research and improvements, we can save maybe some money by not having to use chartered flights. Maybe we could send a heart from Boston to Birmingham on a commercial flight because these organs can stay eight to ten hours rather than spending money. Maybe it will become the cost of doing this transplant cheaper without affecting the outcome. So, these are all very exciting times for our heart failure patients.

Melanie Cole, MS: Well, they certainly are. Thank you both so very much for joining us today. This was an honor for me to discuss this topic with you and really for sharing your incredible expertise for other clinicians. Thank you so much. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.