Right, uh, I think we're ready to move on. Andrew, thank you for stimulating talk. Um, uh, next I'd like to introduce, uh, Andre, uh, Andrew Lotz, who's the medical director of our VAT, uh, program, and Andrew has also had a long-standing interest in the Fontaine circulation. And I, uh, frequently ask Angie for advice on, uh, some of our Fontaine failing patients. Um, so, Angie, uh, again, we look forward to hearing, uh, uh, you teach us on VATs and transplantation options for the Fontaine. So I have one disclosure that's on the slide that's, um, we will be talking about off-label use of various devices. Um, these devices are not being used in the fashions that they have been approved by the FDA for. Um, but my only other disclosure is that as a ventricular assist device community, we don't have, um. A ton of experience at each center and we are getting patients as fast as we can think about them. Grecian, thank you. Um, and so as a community, a ventricular assist device physician community, we are all trying to get our cases together and try to figure out the best way to support these patients, um, and get that done quickly so that we can support everyone that, um, the rest of the adult congenital are sending to us. But I'm gonna be very simple, um, here as I talk about transplant and Fontans, and the reason is, I have 10 minutes, um, and I think that this is probably an entire day webcast. Um, so when you think about, when you think about how I'm presenting this, just remember there's a part to each slide that is probably another hour. Um, so to simplify Fontian failure as we think of it, um, when we're getting patient referrals, is that we think of the early phase, which is right after surgery or in the months post-op, the late phase, which I think is there's something we can do there with these patients, and then the end-stage phase. The end-stage phase is those patients that are long-standing have had PLE, very poor nutrition, thrombus in many different vessels, end organ failure, cirrhosis, and sometimes plastic bronchitis in the end-stage or late phase. So we're trying to prevent those end-stage patients from coming to us and more focusing on that late-stage, um, patient and what we can do for them. Quickly, the early fontan failure, I'm not gonna focus on too much because I think this is, this is the case, the 4 year old girl, um, post-op day 15 from an extra cardiac fontan that is doing very poorly post-op, pancreatitis, pleural effusions, fluid overload, high fontan pressures on cath, um, may not be a great, is not a great transplant candidate and need to think about other things that you can do. But we sometimes do get referrals for these early fontan failures. And so just thinking about these patients, um, are they the best transplant candidates when we're talking about a limited organ, um, or a limited number of organs. This paper, um, I can't see very well, but, um, is from Dan Bernstein from 2006, and I, uh, it's a little bit old, but it really is the largest Fontan series that is multi-centered. Looking at Fontan outcomes and the risk factors in this paper, which we'll talk about on the next slide as well, really was is looking at who does poorly in the Fontane cohort and those patients that are requiring mechanical ventilation at listing. Our younger age, you know, status one, so on the highest um status for getting an organ, and shorter time interval from Fontan were all risk factors that were significant for the failing Fontan transplant outcomes. This graph just focuses on, um, once again, Bernstein's study. This is the pediatric heart transplant study group, which is, um, multiple up to 100 sites looking at all of their Fontan, um, outcomes. If you look at the upper left here, a, um, if you're on a ventilator at transplant, you can see the outcomes are much poorer or much worse, the less than 4 years or 0 to 4 years of age, and then less than 6 months from your fontan. Um. All vote for poor transplant outcomes. But what about these later fontan failures? I think this is really the group that we as transplant physicians and VA physicians need to focus on. These are the patients that are coming 10 years, 8 years out from their fontan. They have had PLE, but it hasn't been long standing. They may have plastic bronchitis, but their end organs appear well. But they may, may have myocardial dysfunction and have some evidence of um diastolic and systolic dysfunction in some symptomatology. Are these patients good transplant candidates? So there's been multiple single-center studies um looking at the transplant outcomes with Fontan. Um, this is just a highlight of one of them, and I just highlighted the conclusion that really talks about, you know, if you pick the right patients, they do just as well as your other dilated cardiomyopathy patients, um, post-heart transplant. So the late Fontane patient. So this is just a case of what I'm thinking about when we're thinking about a Fontan that may be a good transplant candidate. So you have a 12-year-old boy, he had his extra cardiac fontan at age 5. He's 35 kg. He's referred for protein losing enteropathy, maybe has been admitted a couple of times to the hospital. His albumin is 1.5. He gets routine albumin infusions. And it's been a pretty short time since diagnosis of PLE. He has no anatomic abnormalities, but he does have severe myocardial dysfunction. His EDP's elevated to 15 without Brian's fluid bolus. So, just focusing a little bit on protein losing enteropathy and how it affects our transplant and bad outcomes is that you're accruing risk factors as you're having these kids sit with PLE. And so although we sometimes let them um come in and out of the hospital for years and years, they're slowly getting more edematous. They have low albumin, poor nutrition, um, electrolyte disturbances. Their IgG levels are low, so they're getting more and more infections, and they're becoming malnourished. I think this is really important to think about. They're also prothrombotic because all of these bullet points are very important to our transplant and our bad outcomes. So if you have a patient that's been sitting with PLE for 5 years and then we wanna put a VAT in them, they're very prothrombotic, and I think Doctor Palumba will talk more about that in a little bit. Um, and so you've had a patient that's been malnourished, now wants a transplant, now thinking about a VAT, and they're in very poor shape. So when should we refer patients with PLE and should we continue to attempt medical management? And what are the PLE outcomes? So I, I assume during this morning, someone else will present this data as well. So I'll briefly just um highlight that these are the two PLE studies that we in transplant quote the most, that the older study um by Martin's Luke was in 1998 looking at um PLE patients, and there was about a 50% survival at 5 years after diagnosis of PLE. Or more recently in 2014, um, this paper showed that there was an 85% survival five years after diagnosis. But if we're somewhere in between. Sorry, I'm losing my oh. We're somewhere in between. Um, we'll have to think about the transplant outcomes and what those, um, compare with the um PLE outcomes. And then plastic bronchitis, um, so we talked a little bit. Everyone's kind of touched on it this morning, but is it a reason to send patients to, um, the transplant team as well? This is um Schumacher from Michigan's uh paper looking at freedom from death or transplant in those patients diagnosed with um uh plastic bronchitis, showing that there's a 50% mortality at transplant at 5 years. You can see the cast to the right. And having taken care of a handful of these patients that have gone through to transplant, they do do very well post-transplant. Um, the interesting part is how they wait and they're waiting at home with these casts having respiratory insufficiency at times that's pretty severe. Um, so how to get these or coming up with a good plan for how to refer these patients into the transplant team and then how to, how to, um, support them while they wait. So, how do we compare the PLE and plastic bronchitis outcomes to the transplant outcomes? Um, so this is not meant to be able to read quickly, but just looking at that last green line, if you look at all the single study, or some of them are multi-study, small, pretty small studies though, um, of the mortality rate of transplant post if you had a fontan, it's about 80% survival at one year. So if you look at all pediatrics, 1 year pediatric survival, 92% is really what we quote right now across all centers. 5 year survival, 86%. And then in the Fontans, if you kind of collect all your data and think about this and what patients they are, it's about an 80% survival at 1 year, 5 year survival of 75%. Once again, this is taking into account all of those early fontans that were transplanted that may not have been as good of candidates as some of those that are later. So just summarizing those post-transplant Fontan multi-center studies in the interest of time, um, most of them show that there's a higher weightless time and mortality when you're comparing them to dilated cardiomyopathy, and we'll highlight why this is in a minute. The standard listing criteria really underestimates their degree of illness. There's increased risk for early graft failure post-transplant. Death from sepsis is more common. Bleeding is more common since they're multiple time redo, and then PLE does resolve in survivors, which is important to note, and plastic bronchitis. So just to highlight this concept, because I think it's very important to those in the room who don't take care of patients waiting for transplant, is that Fontane with PLE will wait a long time. So while you, um, as congenital physicians may hold on to your PLE patients and want them transplanted in a certain time point, they will sometimes wait for years. And the reason is, is that if you see on the left here, There's been recent status changes to the pediatric allocation system, which I highlighted in red. If you're a congenital and you're on one drip, you can be a 1A, but you have to be in the hospital. So that will take all of our fontans that are PLE and plastic bronchitis that are not on drips to a status 2. They will not even be a 1B. In the old, in the old days, about a year ago, we could potentially put the patients on a little bit of dopamine or a little bit of milinone and send them home, and they would be a status 1A. That no longer is the case. So all of those patients that we've, you may have heard about that small, um, low-level dose dopamine helping PLE can no longer go home like that. So I don't know if this got to the polling question or Was this, was this a polling question for them? Yeah, so, um. Let's see. Mark, can you see the polling results for that one? I'll talk about it while you pull it up. So this is the 12-year-old we just talked about, 35 kg patient with dysfunction. He was waiting for transplant, as we talked about as a status 2 taking forever, but he comes into the ER with one week of difficulty breathing. His creatinine. Doubled. He has a headache and he's vomiting. He's intubated with good respiratory response. His lungs are very low vent settings, great compliance. He now has poor urine output and escalating on his drips, but as I said, listed for transplant. If you were going to use mechanical support, what device would you consider? You want me to just go on? Yeah, for now, go on and we'll get to the, it usually takes about 30 seconds to get the results, OK. S I cannot see this. So That it's better. OK. So our patient has poor cardiac output but good respiratory function. So what would we be thinking, um, in the bad community for the most part and definitely at Cincinnati Children's, um, if it's an urgent placement, which this child seems that he needs some urgent mechanical support, um, we are now for the most part using continuous flow. Um, short-term devices, Centrumag in particular, some institutions use the Rotaflow, and this will support them for weeks to months to get to transplantation. Or if you really want them on a durable device, don't think that they're think they're going to wait a really long time, so they have a high PRA or there's some they haven't been waiting very long. There's a reason, and you think durable support is the right way to go. The Berlin Heart is still available for all the small kids, but most of our fontans are bigger, so we're going towards the hardware. I would say in a Fontan, we're safely putting hardware in 25 kg single ventricles. There's lots of institutions, including ours, that may even push the envelope down to 15 kg, but continuous flow for these single ventricle physiologies really seems to be working. Very well compared to our Berlin data. And then the other option, if you're over 35 kg, probably about 35 kg, this is um what work we're doing with the Synchardia trial. Could you get a total artificial heart and actually take um all of the, the ventricular mass out and support the patient with a synchardia? So there's a paucity of multi-center published data for bads and single ventricle. As I said earlier, that's something that we as a bad community are working very hard at trying to figure out the best way to support these patients, and we're working very quickly, um, since it's a growing population. But what you see here is, is slightly embarrassing even to present because it's so small, but the high, the top table is the X Corps or Berlin heart data, stage 3 being their Fontaine, there's 5 patients, 3 survived, but look at the days on support. One only was on 1 day, 1 was on 3 days, and one was on 229 days. So really not a great population that we have a lot of data on in that with the Berlin Heart. Below this is the intermax data, which is our large adult registry looking at single ventricles is the green line, and you can see that there's only 17, so hard to take much away from this, and the device that they were supported with is not clear in this registry. So the, the uh poll results are up now. Mark, can you throw that poll up on the screen? Uh, it looks like, um, 45, almost 45% said ECMO, um, 11% said Synchardia, 22% said HVAD, and 22% said Berlin. So I think that's a perfect example of how, um, much we don't know about the best way to support this patient. Um, very unclear by the audience of what the best way. would be, um, I think going to ECMO, I don't have it on my, uh, my graph because we, if you don't need respiratory support, we really feel like supporting an organ that doesn't need support, we should probably veer away from. Um, but a good option for some institutions. And then the HVAD, as I said, size-wise, he could fit. Um, so the real question is not only what devices should we put in these patients to support them both long and short term, but are we going to make them better? So which patients that are failing Fontan can we make better with mechanical support? So can we support and resuscitate their in organs? Can we rehab the patients so they're a better transplant candidate? Can we desensitize them on a ventricular assist device or an artificial heart? Can we resolve their PLE, get them better nutrition? Can we get them home so that when they're waiting for a year or two that they're at home waiting? And then the obvious is that they would become a higher status, um, which is never a reason to do something, but it is a benefit. So the end stage, as I talked about earlier, these are the patients that um we're getting uh very late, very hard to help. We start to think, are they not a candidate? You know, these are the questions that we're talking to our adult colleagues about. Are they a heart, liver transplant candidate? Are they just a heart? Could we put a vat in them just to get them chronic therapy if they're not a transplant candidate? Is the syncardia the right thing to do to try to resuscitate any of their end organs? So, and just a quick note on synchardia, we talk a lot about synchardia for late failing Fontans. We talk about it at every meeting that we go to, but the important point is that only 2 have been placed in single ventricles in the US. This is a picture of this animation is of a patient that had asyncardia with a single ventricle, had a capacitant chamber that was built, um, because you do need the two AV valves or you need to deal with that in some fashion. Importantly for everyone to know is that there is a smaller device now, the 50 cc Synchardia device, so the smaller fontans will have that option as well. And why early referral? So once again, an adult waiting transplant on medical therapy. This top line shows all adults that are status 2, which is where your PLE adult fontan would be. Um, only 30-40% of all of those patients status 2 would get transplanted in one year. And if you look at the congenitals, Um 1/3 of those patients with congenital heart disease in medical therapy, this is not all just Fontan's, um, would be transplanted at 1 year. So 5 opportunities to improve our peri-transplant outcomes for Fontan's. I think we really need to think about the surveillance of end organs and early referral. And since there is a paucity of organs, we really have to think about what patients are ready to go towards transplantation. Sharing experience, as I said, we do have a um advanced cardiomyopathy learning network that's now up and running that we're trying to share our experiences with Fontan and VA to understand which patients will benefit from a VA and what the best support strategy is. So not only what, where, what device we should use, where should we cannulate the patient, and then how do we get them home. We're advocating for alterations of the organ allocation system. The adult allocation system is going to be a little bit more in our favor. The changes that are going to be made, but the pediatric was just changed and was not in the Fontian PLE plastic bronchitis favor. Um, earlier referral for late Fontan failures before they're in stage. I think we need clear criteria for transplant referral at each center and then across centers, and then a seamless collaboration between our transplant teams and our congenital teams. Come on. Thanks Andrew. Um, um, as we transition over to Rick's talk, uh, I, I wanted to ask you, um, You know, one of the, one of the things that we, uh, in my opinion, we don't do enough of or consider enough is destination VD therapy. And you and I have had experience now with a few patients, and it's messy when you consider the real patients to have that in. But increasing our patients have high PRAs by the time they get to adult life, um, And, uh, you know, they're in a lot of bother with end organ disease. Can you just speak a little bit to the issue of destination therapy for uh uh in this patient population? So, as pediatric bad physicians, we've really used destination theory more. We've kind of changed the lingo to chronic therapy, thinking that they can. You know, go in and out of their status. So if you place them as chronic therapy or destination therapy, could they still go towards transplantation? The reason that's important is if you don't label them destination, you're always thinking you're trying to get them to transplant candidacy, which maybe would be a longer um life, prob probably better quality of life, although that's yet to be determined. Um, I think then you can place a device with hopes to make their end organs better, resolve their PLE, get them better nutrition. Um, with the hope to get to transplant candidacy. Um, I think the real, where we, Grecian talk, you and I talk a lot about patients is that what bad would help them, I don't think we always know yet. Um, and will it help them and will it improve their quality of life or get them, give even get them out of the hospital. I think because of the small numbers, um, just to highlight the small numbers, there's only 20 or so fontans in all of Innermax and PDMx, which is the two VA registries that we have, um, to even study. Do you think the inflow, you know, having the inflow from the atrium as opposed to the, the ventricle kind of changes the, the spectrum of patients that become eligible, you know, the. And I'm thinking, you know, the whole diastrology issue is a really big deal for, for the fading fontan. Does that change your spectrum of eligibility a bit? So we've been talking a lot about that in our restrictives as well as our fontans. If you have a small left ventricular cavity or single ventricle cavity, can you put the vat in the atrium? I think it depends on the patient. There is a handful of patients that have been. Successfully supported with Fontan's, um, with an atrial cannulation, um, but learning from our atrial cannulation in the restrictives with the Berlin data, um, they do not do as well as a ventricular a canulation. So I think that's yet to be determined in the Fontan and we are extrapolating data from our restrictive experience, um. But as I said, there's been a couple that have been successfully supported that way. And the reason is it will allow flow into the vat where the restrictive or small cavityed ventricle sometimes clamps around it and not, does not allow it to flow. We've definitely seen that phenomenon. Thanks, Andre.
