Adult patients with CHD represent the fastest growing segment of adult cardiology care at 20,000 new patients per year. Heart failure is the leading cause of death for this patient population, but transplant rates remain low. Guest speaker Dr. Jonathan Menachem, with Vanderbilt University Medical Center, explains why that is and how we fix it.
Phoenix Children's Grand Rounds - January 31, 2023. CME credit provided only for participation during live sessions.
Me, I think I know everyone in the room but everyone online. Um Jordan Arabe, I'm Director of the Adult Conde Disease Program here at Phoenix Children's. It's really my pleasure and a privilege to introduce uh Doctor Doctor Meno uh to give Graham round today. Uh Doctor Meno is a, is a good friend of mine. I was doing the math last night and known each other for, you know, just of 20 years. Uh so not quite 20 years yet. Um but uh doctor MDO did his medical training and he went to medical school at Tulane University and then completed an internal medicine residency at Duke University. And after that, uh went to University of Pennsylvania where he completed an adult cardiovascular disease scholarship. And after he completed his adult cardiovascular disease fellowship, he really carved out uh an area for himself. And Taylor made his advanced training combined in adult heart disease and uh and to advance heart failure and transplant and really focused in on that area, which I think for a long time has, has uh been lacking in our um sub specialty area. Uh And I think we all anyone who does adult and ja heart disease does some heart failure, does some transplant, but not everyone does it well. And he said, you know, I really want to do this and do it well and figure out how do we, how do we get these patients surviving into transplant and surviving transplant? So once he completed his training, he um uh started at Vanderbilt where he's now an associate professor in the departments of internal medicine and pediatrics. Uh He is the director of the uh uh congenital cardiac therapies um division and associate director in the uh heart failure and transplant division. And he's really can be credited with really starting their adult congenital heart transplant program and building it up. And in a relatively short period of time since he's been there has turned it into a national referral center and an expert center uh in uh heart disease transplant. Uh And uh he's really one of the, I say one of the really the world experts now in John heart disease transplant, he's written extensively on the subject. He's frequently requested lecturer. Um And it's really been a pleasure and a privilege to hear him today talk about uh transplant in these donor population. It's always a little scary when your good friends from a long time introduce you. You don't know where that's gonna go. That was, that was really nice. Uh Thank you. So, thanks for having me. I'm gonna talk to you about this, an intersection between adult congenital heart disease transplant. Uh Here, my disclosures and I do have to tell you that. I'm pretty excited to be here because we're doing this in person. And when Doctor Franklin calls you and asks you to give a talk, it's just kind of a big deal. So, uh I'm really excited to be here. Thanks for having me. I'm just gonna talk to you a little bit about how I got to where I am. I grew up in New York, which also you should know, I, I talk with my hands and I walk a lot. So if the zoom people can't see me, someone texts, I guess I'll try to stay still. And so I was a Duke undergrad and then I did investment banking and decided that wasn't for me. And then I worked for a medical device company as sort of a bridge to going uh to med school. But somewhere along the line, I've read this book called a Walk On Water about Roger me as a surgeon at Cleveland Clinic and what they were doing for pediatric uh for kids with um with congenital heart disease. And so then I got to Tulane Jordan and I were the first class right after Katrina, which was quite an interesting time to be in New Orleans. And while I was there, I did my pediatric uh med school time at Oxner. And so Oxner had probably the biggest congenital program at the time and, and um doug moody who we were talking about at dinner last night was one of the people there who said to me, you know, if you're really interested in both adults and congenital, then what you gotta do is you gotta go to Emory and work with Wendy book while you're a med student because she's doing adult congenital heart disease and sort of one of the experts in our region. So I went there and Wendy had also done transplants. So this sort of got the bug in my head. And long story short. So I go to Duke where I worked with Tom Bashore, um who is trained, credited for training a lot of uh Wayne was there. Uh um a lot of Anne Marie Valente Joe Kay, there's a whole bunch of leaders that have come through Duke. And then I went to Penn where we sort of carved out this niche of combining uh adult congenital heart disease and transplant. And I, I think this is more geared towards residents of fellows. But my goal was to do adult congenital heart disease and know a lot about heart failure and transplant. And one of my mentors at Penn was Mariel Jesse, who at the time was the president of the A H A. And she told me you're doing this wrong. She said nobody in. She said there's a lot of people in adult congenital heart disease that are interested in heart failure transplant. But there's very few people around the country around that are, that are in heart failure and transplant as their primary focus and are trained in congenital heart disease. So we sort of revamped everything. And in four years, I did both training and now I'm in uh Vanderbilt where I am in the uh adult transplant world, but I focus on um failing congenital patients. That's sort of a long way to tell you how I got to where I, so let me just tell you, I like to start, you guys all know this. But from an adult side, I always find this fascinating when you look at congenital heart context is that in Osler, right? The big principles of medicine, there were essentially four pages given to congenital heart disease, which essentially said there's nothing to do. They all die. And now, as you all know, this is the fastest growing segment of adult cardiology. So there's 20,000 new patients per year that are coming to the adult side with congenital heart disease. And there's actually more um there's more adults, right? With, with congenital heart disease than there are kids. So it's a fast growing area. The problem we're finding though is that now the biggest, the number one cause of death for adults with congenital heart disease is heart failure, but they're not undergoing transplant. We're gonna talk a little bit about why that is and how we fix this. So when I got to Vanderbilt part of the way I got to Vanderbilt was Mariel Jessop's closest friend, uh, is, uh Joanne Linden Feld, who at the time was the president of the HFS A. And Mariel said to me, you go work for Joanne in Nashville. And I said, I don't know anything about Nashville other than it's known for country music and I don't know anything about Vanderbilt. She said go work there because this is how your mentorship and how we're gonna get you to where you wanna go. So when I got before I got to Vanderbilt in the five years before I got there, there were only two adults with congenital heart disease that underwent transplants. And so I sat down with Joanne and we sort of planned this whole thing out of, we gotta fix this problem because we know that that's not, that's not nearly enough. So we define what are our goals and how we're gonna define success. So number one was, we were gonna figure out how to find all the patients, they gotta be there, but where are they? Then we're gonna figure out how to improve patient care, which is an ongoing problem and then grow our research efforts. And then we're gonna sort of figure out how to mix all of this together. Excuse me. So let's talk about finding the patients. That was the easy part. So I got to Vanderbilt. I said, well, we're gonna, we're gonna start it in Nashville and we're gonna look just at the children's hospital here and that's where all of our patients are gonna come from and turns out that's not actually the case. We've now had referrals from all of these different, um, states. I'm, I'm partly here in hope of getting a red dot in Arizona. But, uh, but what we, um, what we found was there was a need and that, um, these patients were, were coming from all over to be evaluated right now. Um And I'll show you more of the data later in the talk, but we're evaluating between two and four congenital patients per week for transplant. So clearly, that has grown, then we gotta figure out how we can improve care because one of the things was that we looked at this and gave Hernandez as one of our fellows who's now at the University of Mississippi, was that outcomes don't tell the whole story, right? So when he looked at the NIS data base, which you all know is not a perfect database. Jordan can go into why? Statistically it's all messed up. But um what we know is that well that everyone says, well, congenital heart patients don't do as well. Well, a lot of that mortality is early mortality after transplant and a lot of it is existing in the Fontan patients and a lot of it then one more step is when we're getting these patients. So we said all right. We got to take a step back and figure out identify which patients are at highest risk and how we get patients safely through transplant. So I came in really excited. We're gonna just do this. And this was the first patient that we did a Fontan who underwent heart liver. This is James. He was a hypoplastic with ple uh his kidney function was sort of crummy and he did awful and he didn't, he came out on ECMO after going back three different times for bleeding and he subsequently died. And um we think about James all the time and I always start by talking about him because we learned a ton about what we were doing wrong and what we need to do differently. And so we went back to the drawing board and said, all right, we gotta rethink about risk, we gotta rethink about surgical plans. We gotta think about how often we're gonna see them and I'll show you what we've done. But the other major thing that we learned from James and, and I won't read all of this to you. But when we talked to his mother after the fact this was something that our team struggled with a lot because they said, oh my God, look what we just did to this kid. He's, you know, this has been a horrible death. And as all of, you know, to take care of congenital heart patients, these patients and families have been told, they're at least from the era that I'm seeing them, they've been told they're gonna die their whole life and they're not gonna survive. So, the patients and families, when they're feeling bad, they're willing to undergo this risk and it's not like we're doing things to hurt them and they're on board. So we said, all right, let's, let's sort of revamp this and think about how we can do this. So we started by saying, all right, let's, let's look at patients based on anatomy. And so I don't, it's nice when you give these talks to congenital folks, I don't have to go through all the specifics. But anyway, um we started thinking about, right? How are we gonna look at them from a risk perspective based on anatomy? Right? And I think this is important for centers to realize is that when you think about transplants, surgeons, I'm sure will tell you like transplanting a te of is way different than transplanting a Fontan with PLD that needs a heart liver. So that was one thing we, we looked at is how we're gonna risk stratify them. And then we also looked at all the different risk factors about things that make them high risk going in. How does ple um work in here? How does sensitization, what's the role of pulmonary hypertension? I'll spend the rest of the talk sort of talking to you about how we've looked at some of these things and then we had to develop the team to do this. And what's interesting is so when I got to Vanderbilt, if you think about an ach D patient, this is all these are all the teams I could possibly fit on the, on the, on the slide, but it's all these different people, right? And all these different teams that have to take care of these patients. When I got to Vanderbilt, these were all there, which was nice. They just didn't have one lunatic who wanted to pull it all together. And so that was my role when I got there, we formed a group of the advanced congenital cardiac therapies, which was sort of a way of us saying, OK, we're gonna be, we're gonna quarterback this team and figure out how to get all of these patients uh to the right people and evaluated by everybody so that we can improve their outcomes and then we want to focus on. So now going back now, how do we, how are we gonna be prepared? And I, I start with this because we um we wrote an editorial about a paper and you guys were probably involved in this where they looked at, they looked at um Fontane patients in the pediatric population. And I think pediatric centers have done a way better job of collaborating and, and providing data across centers but said, well, if you have a Fontan patient, how many of them need to see a heart failure doctor, right. So I would argue and I think most of you would agree that heart failure is, is the final common pathway for most Fontan. Ok. So if we all know that they're gonna develop heart failure and they're probably a large number of them are gonna need transplant or mechanical support. I would argue that it'd be beneficial for them to see a heart failure doctor. But in what you'll see here is that mol uh 45% said they don't need to see a heart failure doctor. Uh despite we all recognize where they're head. So if you extrapolate this to adults, it's even worse because at least in pediatrics, everybody's been trained in congenital heart disease, in pediatrics. It's I mean, in the adult world, it's way different because, you know, uh there's very few people outside of congenital that are paying attention to these patients. So I said, you know, we gotta get people around the country and, and around our region to focus on the fact that these patients don't fall off a cliff, right? Everyone always talks about, well, these congenital patients, they fall off a cliff. And what I would argue is it's all about knowing where the cliff is. So when we use this from a big power stand, so we use this Steamroller reference like, oh the steam roller is coming, these patients are gonna die. Well, it all depends on how far away you are from the cliff. So there's no really need to panic if you know what's coming. And so I think we need to be prepared. So, how do we prevent the fall? So, one of the things that we've done is we use a lot of cardio pulmonary exercise testing and, and Sasha and that grew up in, um, in Boston when he was there has done, has done a lot of work on this. And I think essentially what you'll see is that the patients that do worse as, you know, on uh exercise testing, uh have worse outcomes or increased risk for death transplants or hospitalization. And what we've used is we've used their, the change in, in, in uh exercise testing. I don't think the numbers on their own tell you the whole story. And so we'll frequently put our patients as we think they're getting worse even on the treadmill every 3 to 6 months to see if we can pick off changes. And we don't just look in changes in peak bo two. We also look at, uh, obviously saturations, we look at slow, but we also look at time because time on a treadmill if you're able to do 10 minutes on a Norton protocol, and then six months later, you're only doing three minutes, that's a big change. You know, there are barriers to this and we looked at this when we were at, um, at Penn. Is that one of the problems in getting patients referred to heart failure and transplant. When we looked at barriers is that people will often say, well, we know that we know the data in the adult world of based on Donna Mancini's historic papers on, you know, peak vo two greater, less than 14 or less than 12, they're on beta blockers. So we don't, we don't want to send them to you until we reach those thresholds because you're gonna say no. And what we showed here was that of our 20 patients at Penn. Um Only one of those patients had actually met that peak vo two number. So this tells some of the story, but it doesn't tell the whole story. We focus a lot on arrhythmia and that we didn't always um in the beginning um I hope I don't insult any of my EP colleagues, but you know, the um the ablations are not benign. And um and we see this outside of congenital heart disease, like, you know, sometimes if the third BT ablation doesn't work in our cardiomyopathy patients, it's probably the fourth one. It's not gonna work either. And so we gotta start thinking about things and this was a patient who was a Glen, a repaired Glen who was blue, who under was listed for transplant, who underwent a, an a fib up at Penn, one of the best EP departments in the country. And then she subsequently developed a te fistula. Um uh Yeah, tracheole that had developed on the atrial cuff. So we transplanted her. She did well. And that one remaining part that was from the old part that stays a fistula uh developed and she died. And so this has sort of put us on a mission to say, ok, if patients are having worsening arrhythmias, we really need to use that as a warning sign that they may need a transplant or mechanical support. Sooner. We like to tell patient people to plan ahead. And um this is now a direct hit at my cat friends. But you know, this was a patient. You know, we frequently, I think that the field has struggled in the past and that we didn't have options for these patients. And so everybody was always doing everything we could possibly think of to fix whatever we could. And now if we do have options like transplant and mechanical support, we have to think about what are the implications of everything we're doing. So this was a patient. Uh This was a setting um who had undergone AAA follow up stenting of his superior limb, which we do and then, but he didn't get much better for very long. It was about six months and I show you this and this is what it looked like when they took all of this out at time of transplant. This young man almost had a catastrophic outcome in the in the or at time of transplant due to the bleeding and the, the S BC issues that occurred in pulling all of this out. So it's something that has to be kept in mind. We look at, we're trying to look more at labs. Um, high sensitivity CRP seems to be a pretty good marker of worsening. Um, we, although it's not, it's not perfect, but we try to, we don't know how to actually track it is the problem meld I, which is a combination of liver disease and in state and uh kidney disease has been shown as a marker. It's interesting that this was the original data that they did up from Boston. And then the Boston group did another analysis and showed that they don't think that this impacts it. I don't know, I, we don't, I don't wanna use specific numbers. But again, when we start to see liver function getting worse and kidney function getting worse, irrespective of the, the, the number worsening is a sign that we should be starting to think more about aggressive uh therapies. And then ple. So first talk I've done in a while where I don't have to explain ple, which is fantastic. So, you know, what do we do about ple? So, you know, Kurt Schumacher, who probably most of, you know, did this really nice analysis and said, well, ple doesn't affect transplant outcomes and I think that's true and it's not true. And Kurt and I have talked about this on the pediatric side, that's probably true. So if you take a, if you take a kiddo and transplant them, because they're having really bad ple, remember that age plays a huge role. I, I would argue that. So if you take a 10 year old who's had ple and you take them for transplants, they haven't had time to beat up the whole body when we get referred a 40 year old Fontan with ple that is a sick, sick patient. And so we're trying to figure out in adults, how do we deal with ple? It's interesting that um that these patients are the ones that I always make sure that I meet in clinic and not just my partners because inevitably when they get, if they are seen by one of my partners, my partners will say they look terrible. And I'm like, yeah, yeah, that, that's how they're supposed to. We, we got it. But um uh but my group is having to learn a little bit more about what a Font uh failing Fontan looks like and, and the, the spectrum. So what we've done is we've, we've started to think about how do we, what are therapeutic options we can do to sort of fix Poe. So this was a nice paper that was done by an Angela who is now one of our attendees who was a fellow at the time. And this was all based on a Wendy book idea where Wendy started from Emory started putting these patients on minori. And what? So we looked at the patients we had done at uh Vanderbilt and at Emory and what we found was for a variety of reasons maybe which, you know, it's all I should say. It's cytokines, it's all hand waving. But uh it's, it probably a combination of increased blood pressure in increased blank invasive constriction. Um I think it has something to do with um alpha receptors on lymphatics that's been shown by the Michigan group. But what we saw was in a number of these patients when we were putting them on miniature and their alums would go up, their lymphocyte count would go up and their um and their IgG was going up. So we had seen a number of patients that we had listed that we put on minori and that their ple got better and then we delist and there's a couple of these patients that we're now following. So why, why is that important? Well, I think it's important because I don't think that those patients are not gonna need transplant, they're probably gonna need transplant at some point. However, on the adult side, taking a 30 year old, first of all, if we can kick the can down the road and get them longer until transplant is better, but we're now able to say, ok, if we're gonna take someone into transplant, we're now taking someone who's less likely to have a bad outcome due to nutrition or due to infection. And in fact, now we're, we're moving up the the pathway now because we finally got mentioned, uh this paper got mentioned in one of the major guidelines. Uh it's still way down. But anyway, the hope is that this will start to come about. The the group at uh Michigan has done this with dopamine and had really good results. The the problem is as you all know, with dopamine is it involves a pick line in a continuous fusion. So we've been trying to use a little bit more. The other thing we're having to do and, and we've, we've done is to say, ok, let's start using our heart failure medications more and let's be more aggressive. So we know that Entresto works really well in the adult population. Why aren't we doing it in the pediatric or the congenital population? Fontan are a little bit different, but let's say two ventricle patients. And so they finally did this study, um which showed it's no surprise that Entresto improved six minute walk, it improved cognitive function and sleep, which I'm all I'm convinced did two things. I think it improves sleep. I can't prove this, but I think it improves sleep because it helps to decongest patients. So they're not having pulmonary demon in short breath. And I think it improved cognitive function because the patients were less low output and were increasing oxygen to the brain. It's funny that we we got asked, uh a ach a had asked us about enrolling patients in a clinical trial where we would do a randomized control trial, putting our congenital patients on Entresto. And I turned it down simply because we all believe it works. And most of our patients are getting started on it now. So I don't think there's any reason we, we have enough data from adult two Venable patients from a heart failure model to prove that this drug works. And it's safe to say that we should be at least trying it in all of our two Venable patients. What are we doing about pulmonary hypertension? This is another thing we looked at. So there there was a large period of time, right where more of these congenital were getting heart lung transplant, which in case you missed it, it's quite an operation and the outcomes are not as good as hard alone. So, but we're seeing a lot of these two ventricles, specifically the systemic right ventricle patients that have pulmonary hypertension. Is it true? Pulmonary hypertension or is it, is it reversible pulmonary hypertension? So, we looked at this one patient who had come to Penn young man who uh he was uh congenitally corrected, had presented as you see in the, the top line there, he was 33 he's output in it. He's clearly in shock and his PB R was 13. So this guy got presented, he needs a heart lung and then, and then there was like, well, he's way too sick. We, we're gonna send him home with hospice. And there were a group of us that were like a 30 year old guy with two kids. Like we can't just send him home to the hospital. We gotta come up with a different plan. So we have got, we started thinking how do we treat him just like every other heart failure patients that we saw and got our pulmonary hypertension folks more involved. And what we did was we put them on nitro pros and dobutamine. And what you'll see is that as we expected, his cardiac output comes up because he gets decongested and offload. So this was all who group two left sided disease that with enough time reverses in a way that we were able to successfully transplant him with a heart alone. Sometimes they come in way too sick. This guy, we were able to try try this, this, this was a woman that came to see me in clinic and came on a Friday. We admitted her on Monday and then she was bad at the following Friday because she was too sick. But we, this was a woman who we did at heart made three. And for just that sole reason, she was really debilitate, she was really debilitated and had elevated filling pressures and pulmonary hypertension. That was for group two. So we put a bat in her and I'll tell you a little bit more about her story later. Then the other thing is what we're trying to do more of although insurance makes it difficult is is using CardioMEMS. So cardio MS is a well proven uh therapy in adults with heart failure to reduce hospitalizations based on de congestion. So I don't know how often you guys use it kids, but essentially it just sits in the, there you see, it sits in the, in the P A. We can monitor pressures from home and then adjust diuretics. The first woman we did this in was a uh CCTG a dextrocardia who had been admitted about every, I don't know, three or four months we were being eval, she was being evaluated for transplant, but there were a bunch of barriers. We put a CardioMEMS in her and she hasn't been readmitted in three years. She's now getting worse and we're gonna, we're gonna plan to um complete her transplant evaluation now, but it's nice that she hasn't been in the hospital. Sorry. And then we said, when I say we said, Joanne Linden Feld said to me, the research is really important. I was never that into researching, I was into solving problems. Um And I wanted and was pretty decent at building teams. And Joanne said um said we gotta do more research and get this stuff out there for two main reasons. One will be able to change how people think about things and we'll also build collaborations around the country by involving research because research is a really good way to bring everybody together. So like most things I do what Joanne tells, I listened to Mary, I listen to Tom and now I do it, Joanne tells me. So the first thing we looked at was this idea that where should these patients be transplanted? Right. There's all everybody wants to talk about this. So we just said, well, let's just look at it. So we looked at, you know, and it should be no surprise, right? Low volume centers, low volume transplant centers had worse outcomes in transplanting congenital patients. Um Now we looked at this every different way. This has nothing to do with number of congenital transplants. This has everything to do with total volume of transplant. Now, I'm not arguing that congenital should be transplanted where there's no congenital surgeons with no ach D and none of that. But I'm saying that the high volume transplant centers, there's gotta be something that we're doing differently. And I think what a lot of it comes down to is this idea of failure to rescue and ability to rescue in that. Like at Vanderbilt right now, we have an intensivist overnight in our IC U, we have AC T surgeon that's available in house, usually a fellow. So our ability, if something goes wrong to get someone on EO or get them back to the or is pretty quick, which doesn't exist every quick there was this, there's this other thing that uh I have to say I'm guilty of talking about, but Tara had uh published this. Um and this idea that, oh, we need to oversize the donors, right? So this idea that congenital patients have pulmonary hypertension that we don't know how to deal with and we have to oversize the donors because the right part is gonna fail. And so I got to, I got to Vanderbilt and I talked to the surgeons and I said, I don't understand this. I'm happy to do it, but should, why are we doing this? And they said, don't do that, just get us the best heart that you can get us with a short ischemic time. If we can avoid it, let's be prepared. Let's get the best hearts and, and, and uh see which is what got us thinking like maybe we've just been saying stuff that's wrong. So we looked at this Dan Clark who's uh I'm still mad up for leaving us. He's now at Stanford, but he's a phenomenal fellow who does M MRI, he's now uh attending out of Stanford. But we looked at this and you know, and said, ok, how does sizing matter? And it turns out that undersized if you put a small heart in a big body that doesn't work. Ok? But that's, that's not right. But it turns out that if you oversize, you try to put a bigger heart in just to protect so that the right ventricle doesn't fail. There's no, there's no difference in outcomes. And we looked at this based on height weight bmilv mass ratios predicted heart mass. We tried every possible thing and we could not find any benefit to oversight. There's probably small reasons to do it um in certain patients. But one of the problems is if you wait for this perfect heart that you really want, you're extending wait times and the longer we wait to get a heart, the worse the patients get. There's this other idea that we need extra parts. All right. So what does this mean? Our, our surgical colleagues know exactly what I'm talking about but everybody else may not. So the idea that um we're going to the procurement surgeon must be aware of the need to obtain extended donor veins, a order and or pulmonary arteries. And this was a really nicely done state of the art and Jack. Um And I have to say that I have written that same thing in papers that I've done about. We need, we need extra parts. So what does that actually mean? All right. So if we, so usually what we do when I say we, our surgical colleagues do is they, they uh the most of the pulmonary trunks they disconnect. So um when you see that black line, they take the donor heart and they, they uh that's where the cutting occurs. But then the idea is though with a, with a Fontan, as you see, right, the pulmonary arteries have all been disconnected and reenact the most and operated on. So we gotta do it differently. So what we gotta do is we have to, we have to make sure that the donor heart, we get all of the pulmonary arteries all the way out so that all of that piece can get sewn into the, to the recipient. And uh now what, what does this mean? So this is great and our, our surgical colleagues are always happy if we can do this, but this assumes that no one's gonna use the lungs. So if the lungs are going somewhere else, and that means that we're, we're having to wait where the lungs get wasted. So our, again, our surgical colleagues said to me, don't, don't do this. We'll, we manage to ANAs the most and and rebuild the pulmonary arteries, just get us the best part. So again, we looked at this and it turns out there's no benefit looking at uno's data and waiting for where you get the pulmonary arteries. So, um again, wait times this increases the wait times pretty much. Then we decided we're gonna see well and this is what everyone wants to talk about that. All Fontana are the same who needs heart, who needs liver. This is a talk for a whole different day which usually involves people getting angry. But when I was at Penn, we published this that every Fontan that has bridging fibrosis, 100% of them need heart liver. And I was dead set on this and I thought that was 100% right. The pediatric folks, uh Doctor Simpson published this from and said, nope, nobody needs heart liver. They all, all the livers get better and they're all fine. So as I will tell you that my data was flawed. This data is also severely flawed because as we said, a 13 year old getting transplant is way different than a 40 year old. But also we still haven't figured out how we're gonna define cirrhosis. So if you look at these 20 who underwent heart transplant with that seven had cirrhosis, that's cirrhosis by CTC, only two of those had biopsy proven cirrhosis. So I don't know who's really cirrhosis. And then you see that in this group, some of these patients with cirrhosis died. So were they not put in the right group? I don't, I don't know, I'm not knocking this paper any more than I would knock my own my own paper. And just to say that the answer is sometimes they need dual organ because what we've seen is when we looked at our explant, uh Sasha Shaina who was in Vanderbilt submitted this when we looked at our, our explanted liver compared to biopsy lo and behold, it doesn't always match. And sometimes we've seen where the biopsy is F three. So bridging fibrosis and we take it out and it's, the rest of the liver is, is frankly erotic. So, what we've had to do is just pretty much say, which is uh humbling in times is just to say we're gonna trust our liver team on how they want to evaluate this. And we're not gonna hold to um any specific rules about who gets hard and who gets liver. Because, you know, the other thing that keeps coming up is this idea that liver prevents rejection. And this was shown in the, the Mayo clinic did this in five patients and says, well, you know, if you put the liver in, they don't reject. These patients were highly desensitized. I mean, if you look, they all got clicks, they all got thymoglobulin, they all got a TG. And when we looked at our data, we've had a number of our heart livers that have projected early on. And if I, when I get to it, I'm in the paper is sitting on my desk that I have to finally submit, but we're gonna submit this because I, again, I don't think it's, there's a right or wrong, but it's not always the case. And lastly just to talk about how the old idea of like list, we changed the listing process for congenital and said, well, you know, listing is just unfair in adults because look at this, our congenital um in the new system, they're all lumped into, to force and uh they're gonna all die and it's gonna be terrible and, and a looked at this and it turns out that that's actually not true. So this new listing system really hasn't negatively impacted us. What it has done though is it, it's, it's forced us to change the way we're doing things. And so, um I won't bore you all with all the details of, of exception pathways. But uh Aa Raley, who was one of our fellows looked at this and what we're seeing is we're writing a lot more exceptions, trying to plead our case to, you know, and to our surrounding areas to say this Fontane. I know you've got them at a four, but they're way more sick than a, than a four and we need to move them up and we need to get them transplanted. And so far 100% of the time when we've written an exception for a congenital patient, they've been uh uh upgraded on the list. Um I know this is being recorded, but I'll still say this. I think part of that is that usually my exception starts off with one of the, the old school pediatric introductions of a full paragraph of anatomy starting at birth. And I think what happens is when they read my exception, they just eyes glaze over and they just stop reading it just to say yes. But, but in all honesty, I think I think part of the rule is about exceptions is you have to just make your case and just explain to them that when you have a Fontan, it has questionable kidney disease is gonna need a heart liver that's sensitized. Like this is an unstable patient. And then again, this idea that, you know, well, there's no hearts for these patients. And I think, you know, we just have to be aggressive. We talked about at dinner about this a little bit. We're using Hepatitis C hearts in our congenital patients. And then, um this was the first time we did it in a heart liver. Um And then we're also starting to use D CD hearts, which are donors before brain death, which is a whole different uh realm of opportunity for these patients. Um They have no chance of neurologic recovery for those of you that are not transplants. Um savvy. Huh? So I wanna just now take, tell you a little bit more about specific patients because I think, I think this idea of success for significance is really important. I went to a, a phenomenal, there was a, a foundation dinner and Tim Tebow got up there and talked and it as we all know him as a football player, but also he's, he's been very, very supportive of the Down Syndrome community and as, as an offshoot for the congenital heart um community. And so he, he talked about so at this, what he does is every year is that he auctions off his Heisman trophy for someone to, to, to take for six months or a year to their house. And he talked about why he does this. And he says, look, I, yes, it's cool that you can have my Heisman trophy and you can have it there. But the goal is not for you just to have your Heisman trophy and say, hey, look at this Heisman trophy. The goal is for you to have this Heisman trophy. And when someone says, why do you have this Heisman trophy? And you say, well, I use that this came because I donated money to a congenital heart foundation that is doing research for congenital heart kids and, and uh helping the Down Syndrome community. And so he said, I don't want to be someone whose life is focused on success because success is about us, but significance is about other people. You or we can take our success and turn it into significance. And this has really driven a lot of what we've done and how we think about things. And I think you guys would all agree. So I'll tell you a little bit about success. That's not really significant. Um Is that I, in the five years before I came, we had done two adults with congenital heart disease. This is what our numbers have done since then. This year alone in January, we've just, we've done five congenital transplants at at Vanderbilt so far. So overall, we've done 40 transplants. Um and five patients have gotten bad. There's um and there's a couple in the hospital that are currently waiting and I'll just show you this uh because I know everybody's sort of interested in this miscellaneous category. Um uh or my, you know, I think every congenital person has like a favorite lesion and the least favorite lesion and, and uh I really like taking care of LTG A and I cannot stand shows anymore because um I think show and part of that is, is that I think shows is an underappreciated uh systemic illness where patients are way more sick than we ever gave them credit to. And a lot of it has to do with their uh pulmonary function and their pulmonary arterial hypertension. Um And then we've done um the other thing is is that Joanne was right about is that we've had some success in terms of research, but mainly the, with the way we've been successful I think is that we've, we've worked with a lot of different institutions to build these bridges that have brought the patients in. And we've also um included and it sort of forced a lot of our fellows um to be involved in congenital heart training and research because on the adult side, there's only two weeks of required congenital heart training in adult cardiology, which to me is crazy. So, uh of all of these um fellows and residents that you see here, only two of them, uh three of them were actually congenital heart trained or had any interest in congenital heart, which is important because as they go out, you wanna make sure that they know something about congenital heart. And so now I'll just show you. So our, this was our first attempt with James which, who we rethought everything, how we're doing things operatively. Um Planning, we put Sean and Sean on the right. Uh um And we put him on a treadmill every 3 to 6 months and he's uh almost five years out. Now. That was when he celebrated his 30th birthday with his son Mason. He had been told he was never gonna get to 30. So this is a big birthday. He's also a quirky dude and made had his family make the most disgusting cake anyone has ever had in their entire life. I don't know who ate that. But um he's, he's been a big supporter and, and what's amazing is that with James? And this is all credit to our surgical colleagues um games. We pretty much emptied the blood bank, uh two units of packed red cells for that operation. Now, that's not always the case, but there was, there was a different plan going in. I think we've learned a lot. Uh Pete Hottinger was a guitarist, a famous, very famous guitarist um who was from Nashville uh a few years before I got there. He had um congenitally corrected. Um, transposition couldn't get transplanted in, at Vanderbilt because we didn't have the tools of the team. He actually got, um vetted at, he got vetted at um Texas Bud Frasier. Did it. I don't remember where you said. No, he's hard text. Um which likes rub in everybody's nose a little bit. But the, um, you know, this was something where we learned from Pete and this is Miss Go Miller on the right who had exactly the same anatomy. And about seven years later, she's now undergone transplant. I wish she would stay off the motorcycles. Um, but, um, she's done, you know, we learned a lot from Pete in order to sort of propel forward our ideas and how we could be successful here. The truth is that we're in uncharted territory and we've got to be aggressive about trying new things with patients and it seems like the patients are into it. So this was Miss Hodges that I told you about. This was a woman, she's here. Um, she was the woman who was, and I'm sure you guys see this. She was out in the community. Uh, her ep care was being taken care of somewhere between Nashville and Chattanooga. Uh her ep doc was doing the best he could. He just kept upgrading and changing her pacemaker when needed. And then she showed up in my uh clinic and I was like, oh my God, this lady looks like she's, and so this is the woman that I saw on Friday we brought in on Monday and because I couldn't convince her to stay and, uh, and she was vetted on the following Friday. So these patients are out there. These are like ones that we don't even know. Um, so she underwent VAD and then she's now almost three years. Oh, no, she's now three years out from transplant. She, we got this other thing where all of our patients are getting these humongous tattoos to celebrate. Uh um uh it is kind of cool out of all the things we're gonna get angry about. I think we'll leave that one alone. Um But again, we use what we learned from Mrs Hodge for uh Mr Cochran who had been sitting in another hospital awaiting transplant for six months with really elevated pulmonary pressures. I don't know if there was, I, I don't know why. Exactly. It sounds like there was they wanted to transplant him, but there was no real clear way to transplant him. So anyway, he came to us. We thought he was too sick for transplant at the time he underwent bad. And now he's close to almost a year out. He's uh we have a bell that everybody rings when they leave the hospital. So he just said he's celebrated. Now he's now post transplant. I think this is something you guys all see. Um Mr Burns, I feel I feel fine. I'm doing fine, which we usually say, you know, do you really? But as you guys know, when you've grown up with congenital heart disease, you think you're fine, you just get slower and we kept putting him on a treadmill. Uh He was a mustard patient that underwent transplant. He's almost a year out now. Then I think one of the things is you gotta just be willing to take on certain risks and, and try to break down barriers. This is Joe here, Joe is, he just turned 40. He's um Down syndrome, unbalanced canal who was uh Fontane was done um in, in Philadelphia early on. Um and he struggled, we learned a lot from Joe both surgically but also where we had to go back to the drawing board to say, how are we going to deal with a 40 year old Down Syndrome patient? Because uh he would have been best served by all pediatric nurses. Attempt to be honest, not from a medical standpoint, from a psychosocial standpoint. Um If you want to hear more about his story, he was featured on, they did this uh documentary he likes when I tell everybody that he was on television. Um They did a really nice show on Discovery Health about transplant. Um but he struggled as you see, he was on oxygen, having needed a trache. And uh that was right him after a transplant from Philadelphia, he connected us with the, the gentleman to his right was a patient that was also up in Philadelphia on a Fontana heart liver who was sent home with hospice. Joe's family contacted us and said you can't let this guy go home on hospice. So we, he's been transplanted. Um And now Joe is two years out. He's boxing, he's put on weight and he's doing really well living his best life in uh in Philadelphia. So what's camp mono? So we've got a bunch of these are quirky, funny patients as you know. So there was a period where we had, these were so Liz on the left, Liz Camille and Jen were all um Fontan that needed heart liver. Ray was a shows that needed heart liver. Um They were all in the hospital right around the same time. Um And so they all became friends and they decided they were gonna call this Camp Monaco. Um And uh just to clarify, I had nothing to do with this, but this is how they define class mono. Uh But this, this is an important group for, for us to look at because, you know, Liz, um Liz was not our patient. She had come from a Tom Young who was her doctor down. There was one of my mentors going back to med school who called and said she needs help. Uh Ray had been sent to us by UCL A uh Camille. Um is a uh really interesting story. He's from Poland his father was a, a family medicine doc in, in Poland. When he was born, they realized that he couldn't be cared for there. So they moved to the, to the States. They were in Kansas. He was sent to us by the University of Kansas where we have friends. And then Jen is a uh a pediatric uh cardiac IC U nurse up in DC who they told her there was nothing to do. And she told me her favorite word is the F word. So, uh she said, uh I'm going somewhere else. So she came to Vanderbilt and now this is Jen more than a year out. She said she wears a, she always makes sure she wants everyone to see her scars. So they ask her what's going on and, and hear about her story. This was Liz who told me that she, all she wanted to do was try to feel normal. And a year ago, her, her plan was to climb red rocks. And so she just, uh she just, she's living her best life. Now, she told me she, um, the funniest thing was she said was, she said, um, you know, I didn't know that trick or treating could be done easily. And I was like, what do you mean? She's like, why didn't I have to stop and break? Like I went with all the kids, all the houses. And I was like, wow, we really have these congenital have really learned how to adjust and have a new normal. And then this was Camille who told us uh that after all he really wanted to do was be able to hug his daughter. And um this was him celebrating uh uh Christmas this year with his daughter who's growing up. And then lastly, one of the best stories we've had is uh Ray. So Ray was in the hospital waiting for transplants. So he was waiting for heart liver um as it shows he had pulmonary hypertension, um we could not keep him dry no matter what we did. He was very uh uh very diuretic resistant so needed IV dire. So he was in the hospital about three months waiting for transplant. Got to know all of the nurses who all became part of his family. And he proposed to his fi uh now as a fiance on the day of his discharge. So that was, that was quite something he's getting married in July. So just to conclude, I think, um I think how do we change this paradigm? And what are the, some of the keys to success? At least in my mind is one is we got to get to these patients sooner. And I think, I think um I think we make a big mistake to put up any barriers to referral. I tell everyone just send me to patients whenever everyone and me saying you don't need a transplant now is not a bad thing and I'm happy to see them and I think we have to, we have to do more of that. I think we have to do a better job. Um especially on the adult side, I think as pediatric teams are better at this, but we have to come up with a better collaborative treatment option. We gotta stop just saying this stuff and we just say stuff and, and, and get up and, you know, oversize donors and all of this. We don't know if it's actually true. And I think we've got to do a much better job of demanding data and looking at those studies and the truth is it's there. We just just takes a little more effort. We have to try new and unproven techniques, you know, these D CD hearts, hepatitis C. We got a lot of pushback. How can you do this in congenital patients? And the best part is is that like I told you early on with James is that the patients and the families, to be honest, they want to be the first of anything new. So if they're on board, I don't know what's holding us back. And then I think always, and I think this is really probably more important for residents of fellows to think about is that, you know, what we do can be a grind, especially when you're here all the time. But I think sometimes you got to stop and think about the significance of what we're actually doing because we are getting to make meaningful differences in the lives of a number of different patients. And with that I will end. And I'm happy to answer any questions or your comments. I see a lot of people were writing in the front row. I don't know what, so Dave, who's our chief surgeon? Oh, I'm sure he'll start out with an easy question. I share some reason also point. So uh first of all, thank you for accepting his invitation. It's always that you have achieved more than success and you know, at least um taking this pathway um in training here and all these, some of which I've gotten to know some, it was, I'm sure it wasn't easy because that even though you knew there was like at the end, you couldn't see it at the beginning. Um I have some common for you to potentially elaborate and then one actually specific question. Um I'm curious as to um what is the conversation of your surgical team in your location? What are the responsibility? Not only for hearing because I agree with you um delaying and we do that in strad by if the patient is doing OK. I rather wait to na tissue to bring that. Uh particularly when I think of adult con general transplant and embarking on that. If I'm not the one driving, it's very hard to operate through somebody else's hands to elaborate a batch in three dimensional fashion that they're not used to. The best thing that an adult guy, you know, respect his respect can do or does is actually putting two big circles of important together. They're not think, thinking about, you know, and so on, I'll create those batches. So uh we mitigate that also by what we have to do it, we bring the donor cardio or reconstruction. Uh So I'm here on to the composition. Um The current team. Uh by the way, I'm very surprised that somebody took a shot at doing a single go down. Um because that's not the norm, right? Um But also, um I wanna comment that we, I still see the liver as a crazy black box because, you know, you think you can make the call before they cliff. But as soon as you get into the operating room, that's the cliff. Yeah. And, and um and I can see how we just think that the function of the liver or the synthetic function is OK. And then we're now granted, we also found ways to be ahead of that and somewhat, I was somewhat successful and deserved to do that. Um And then, lastly, I'll ask you uh to see if you can share with the team here. What are your measures, preoperative measures to deal with? Basically, it seems that we can connect, we can take advantage of hypertension as a, that's one of the uh uh tools to control hypertension but boy, I mean, it can be very, very challenging to care for these patients even though they do IC U counterproductive for function. So just yeah, so uh let me try to hit all of them. And so we do all of these transplants at the adult center. I mean, Vanderbilt is a little bit different than you guys. So we're, we're sort of, we're connected, it's one hospital system. Um but our IC U, they see uh last year, last year we did 100 and 23 adult transplants. So like our IC U team is used to see transplant. So that's that our surgical team is almost always. So I required that uh our congenital surgeon and our adult transplant surgeon to review the cases beforehand. I'm sort of forced to make everybody work together sometimes, which is not the easiest, although they always do like operating almost. So every Fontane has been done by a co by our adult transplant surgeon and our and a congenital surgeon. There have been one or two like a techology that's been done by one of our senior adult transplant surgeons. But there's always discussions about who who's gonna do bloods. Our to be fair. Our most senior transplant surgeon, I mean, he's been ASHA has been doing this for 25 years and was also a lung transplant surgeon. So like if any of our juniors, sorry if any of our kids, the uh if any of our junior surgeons are gonna be involved then on the transplant side, then absolutely. Our, our congenital surgeons are involved. Ok. So I think, I think all these patients benefit from more, more views. Um That was question number one, question number two about the liver. We don't know. Um, I think it's a, we're doing all of the testing. I think, I think um, the CT scans aren't super helpful except where they've looked when the patients have a lot of varices or have, uh, recanalization. A recan of a can of a, uh, like umbilical vein or something we've said, ok, they're, they're frank frankly c we should be doing heart liver. Um, the, we're doing biopsies on everybody just to sort of match things up. I think. Uh, the last, I don't think it's worth anything. To be honest. We're doing it just to see. But I think the other thing is that really age plays a big role. It's tough to imagine that a 40 year old has had a Fontane circulation for 40 years is not, their liver is ok. Um, but we did do a 40 year old that we did a hard alone or she did fine. So, it, there's a lot of back and forth. It's no easy answer. Uh, I don't know how to deal with the hypertension. I don't think any of us do. I think what we've done well though is we've been more aggressive about putting patients on uh ECMO coast, if we think there's gonna be bleeding issues or hypertension, which I know is not always an indication for ECMO. But what we're finding is is that as you know, like if you've, if you do the heart transplant and then the kidneys start to go and then they're getting their lungs start to get congested, then we wind up with more problems that we started with. So the hypertension, I think we do all the things that you guys probably do, but we're trying to be more aggressive on supporting the rest of the body along the way. And then in terms of your question about Down Syndrome is a very good one. I don't think there's that many of these patients. I think he was turned down by a fair number of centers who were concerned that he was down syndrome. Um I didn't think that was a fair reason to turn him down. Um He had other reasons that centers turned him down to, but um I think if we were going to do that again, we'd have to rethink the training and who was going to take care of the patient. I think I got most of them. So choose the same questions. So one was uh according to the video, do you start to see and is it somewhere related with this? Can I just say yes? The uh we're not really sure. Um I think, I think probably some of it is decongestion. Also, you probably increase the forward flow to the kidneys. They're dire, they've become less dia resistant. Um We, most of our patients are getting put on midodrine now and it's, it's varied. We have some patients, we put them on five of midodrine T ID and they start doing great. Then there's some that have to get up to 20 before and then there's some patients, we have one patient in the hospital. He had no response and I, I can't have no idea who's responding and who's not like how to judge upfront. I do think the other thing that we've seen and we used it in our Down Syndrome patient, Minori, he didn't have complete ple but he was having a lot of aides and in plural effusions and it does help in those cases too to sort of he was on oxygen before we put him on Minori and then came off because his plural effusion sort of started to go away. I think some of it is, you know, it's like magical thinking with Merin, but it, it does seem to benefit the patients. And my second question was regarding the use of micro, how long could we see the increase in pressure? Yeah. Um Well, so if their pressures will tolerate it, right? When we're in the cat level, if we put them on high enough doses of Nipride, they, they should baso dilate enough that you can drop their way at a, now, the problem with that method, right? Is that that's only trans eat. So, I think, um, I, I think that usually gives us a sense of who's gonna respond in the gentleman. We did that for 37 days. We don't typically do that. There was no interest at Penn in batting that patient. Now, looking back if he came in now, I would probably push to bat him because there's really good data that if you decongest patients uh with cardiomyopathy with that uh that their pulmonary pressures were remodeled. So, um I think we should get a, we should get an early signal that they're what type of pulmonary hypertension they have. And in fact, the group in um uh uh in Europe published this, that over 90% of our systemic right ventricle patients that have pulmonary hypertension. It's who group two. So postcapillary pulmonary hypertension that reverses. Awesome. Well, thanks, I was allowed a couple of times. If you're allowed to what I say, it's not a risk. Like, you know, one of the things that I would do is to improve the writing because writing CPR B, we, you're not able to tell us the good data about all of these things that you're learning. Um But it's true that le over the time is dramatically different to the, we see that a big of a problem, you know, I hope so, really big speed because the reason we exception, all people don't realize that over 40% of our PD application, about 3% of spread that out of the program. Um And so this is, this is a great thing for that whole population in the country. But eventually this research, things like this, you don't have to teach everybody else how to have this all in. I wish more people would do it because it's, um it, it's, it's problematic, not just for, I mean, I, we love what we do but, you know, these patients that I'm showing you, like, they have to move to Nashville and it changes their whole, they have kids, they have families, they have been so, um, we need to have other centers of excellence that are willing to undertake this sort of past past time now. Um, I think it was a, it was a phenomenal talk. That's a great question. We all learned a lot. Thank you for having. Mhm. I don't get referrals until they're already. He used to.
