James Cnota, MD - 2024 Fetal Care Center Navigating Perinatal Care for Trisomy 13 & 18

Next, uh, we're gonna have Doctor James Snoda on chat. Um, he is part pediatric cardiologist and, uh, director of the fetal heart program at Cincinnati Children's. He's been at Cincinnati Children's since 2018, and he has an extensive list of, um, NH funding, uh, and that's all for his work with the Clinical Research Center, um, as part of the Pediatric Heart Network and also as part of the Pediatric cardiac uh genomics Consortium. Um, he's presenting a little bit about, um, how to manage, uh, patients with congenital heart disease, um, as it's been one of the more hot topics in terms of management for uh these kids with diag these diagnosis. Uh, thanks, Laura, and thanks for, uh, the invitation to speak, um, uh, to the committee and to those who are participating online today. Appreciate your time. So my assignment is cardiac care in infants with trisomy 13 and 18, and uh I am the director of the Feel Heart Program in Cincinnati. And I've worked with the fetal care team for a long time here. OK. So, most on the call probably know that the association between trisomy 13 and 18 and congenital heart disease is a strong one. CHD is present in 80 to 90% of children. And all types are present, ranging from mild to moderate to severe in complexity. And similar to other prenatal uh diagnosis uh by imaging, the complexity, uh, seen in the prenatal cohorts are typically more complex than those in the post or more severe than those in the postnatal cohort, uh, and that does have some influence on counseling and outcomes. In addition to sort of routine congenital heart disease, one of the hallmarks. Uh, of trisomy 13-18 is polyvacular dysplasia, which is a redundant and thickened, uh, valve. Uh, it can be any of the four cardiac valves, uh, and it can be with or without important valve regurgitation. Typically, it's not an important driver of cardiac symptoms, but maybe most importantly, it points us towards the genetic diagnosis based on the, the imaging phenotype. Uh, the role of prenatal diagnosis, uh, in congenital heart disease and more broadly in the trisomies, uh, first of all, it can be a, an early clue about, uh, the overarching diagnosis and may inform subsequent testing. And then importantly, because it's certainly not the only, but it's a major contributor to postnatal outcomes, uh, and the fact that the complexity does range quite widely, uh, the anatomic details are important to families, uh, when they're critical to our counseling because it, they, uh, influence. Uh, not only survival but quality of life in important ways. And so we need to have specific diagnoses to help families with their decisions. Uh, it informs the prenatal care and delivery planning. Um, specifically, you know, I think in the real world, what we see is that it's part of the family's decision about whether their care goals are aligned with the institutional approach. Uh, which is incredibly important, and the prenatal diagnosis lets that discussion occur at an early time point when they have options such as second opinions. And then it also guides delivery planning and in our congenital heart disease world, we, uh, describe this as the CHT levels of care based on disease severity. Uh, of course, it's part of the bigger picture and there may be other, um, aspects of the prenatal diagnosis that drive Um, the delivery planning, but this is certainly one of the important elements. Uh, as far as the distribution of congenital heart disease, um, and this is in the postnatal population, uh, in trisomy 13, the most common lesions are lesions that result in left to right shunting with, uh, the patent ductus arteriosis, um, accounting for 32%, atrial septal defects, accounting for 27%. Ventricular septal defects, 28% and all three of these, for those who aren't. Cardiologists, you know, they result, and neonatologists who understand this well, they result in, uh, blood from the systemic circulation, the red side, uh, passing through the lungs, leading to extra blood flow to the lungs. Uh, and so they're described as left to right shunts. Uh, the most common right to left shunt is tetrology of flow, just, uh, depicted in the bottom right corner, which is where there's important obstruction to pulmonary blood flow, allowing the blue blood to cross over to the left side, so a right to left shunt, and this results in, um, cyanosis. Depending on the severity. In trisomy 18, uh, by far the most prevalent diagnosis is ventricular septal defect. You know, for us prenatally, all fetuses will have a PDA, so this is not a diagnosis that we can make prenatally. Uh, the same is true for the ASDs because all babies have PFO. And so these two images show a big hole between the two ventricles right here, uh, with the blue and red flow going back and forth through the hole, and that's a large ventricular septal defect. It's fairly typical of trisomy 18. Um, Both of these diagnosis also can have uh other complex um lesions which we'll talk about in some of the surgical data. But the most common are simple shunts. So, uh, these are non-cardiac considerations or most of them are, uh, that are important for cardiac surgery discussions, however. And the first that I'm gonna highlight is the prematurity and low birth weight that is associated with the diagnosis. Um, starting with the bottom table, these are multi-state state birth defect registry data on gestational age. Um, Uh, and you can see the distribution there, uh, increased rates of prematurity, but importantly, uh, where that intersects with cardiac surgery is in the figure, uh, above, and you can see there's a very steep inflection as gestational age goes up. And a lot of these babies are, uh, the top line is the congenital heart disease population, so this is all comers. It does include, uh, patients with trisomy 13 and 18, but it's a small portion. The bottom curve. Our, uh, uh, babies without congenital heart disease and with the incredible success of premature newborn care, you know, they do quite well. Um, at lower gestation, but there's a big gap between the cardiac patients and the non-cardiac patients in survival, uh, particularly in this sort of 28 to 33 weeks gestation range where unfortunately, a number of these babies fall. And this is an important factor as we counsel families about whether surgery is likely to be helpful to meet care goals. Um, of course, extra cardiac malformations are an important consideration and add risk, and the one that I would highlight is the airway in particular, that is a, a challenging, uh, problem when it comes to cardiac surgery, uh, and, um, uh, uh, liberating patients from, uh, mechanical ventilation if that is the goal of surgery, uh, in many cases with simple shunts. Um, but the airway, uh, is a complicating factor. Uh, pulmonary hypertension is unique in this population in the sense that it is, um, early and accelerated in onset. And as we'll talk about in later slides, this observation is an important part of what is guiding. You know, the current trends and uh timing of cardiac surgery. And then I, I added something that's not well described in the literature, but we've observed and have investigated and are working on reporting in our institution, which is myocardial dysfunction seems to be a little bit more common in this patient group and adds some risk. Uh, to cardiac interventions. Um, the postnatal clinical manifestations that have to be managed, uh, by the family, um, and the clinical team include congestive heart failure symptoms from the left to right shunt, too much blood flow in the lungs, reducing lung compliance, and increasing work of breathing. Uh, and causing respiratory insufficiency that can be a contributor to the need for respiratory support. Uh, it also contributes to heart failure, contributes to poor growth and feeding intolerance, and while, um, these babies can have those symptoms independent of the cardiac disease, uh, the increased work of breathing, uh, does, um, it's a contributor to these, uh, challenges in babies with trisomy 13 and 18. Uh, the right to left shunting from outal tract obstruction such as tetrology leads to hypoxia, and that You know, for anyone who's in a NICU who's taking care of these babies, they know that that interaction between airway obstruction and pulmonary blood flow obstruction is delicate. And right to left shut left shunting at the ventricular level with resulting hypoxia occurs very easily with a little less bit of airway obstruction or uh hypoventilation. And so that combination is uh requires a delicate line to walk uh for the clinical support. And then lastly, a few more words on pulmonary hypertension. The etiology of this arteropathy is not completely clear. Um, some of the babies do not have the normal physiologic drop in pulmonary vascular resistance, which, um, greatly increases their risk, uh, if surgery is being considered. Uh, furthermore, when the left to right shunt does occur, uh, that shunt, uh, is also believed to accelerate an early onset. When I say early onset, it For kids with a big VSD who don't have trisomy 13 or 18, we don't really worry about a fixed pulmonary vascular resistance problem until well into the first year of life. Uh, but this can happen much earlier in the first months, uh, in trisomy 13 and 18, and I think it's shaping some of the new thoughts around, uh, how and when to offer offer cardiac surgery. But I will point out that if there is high pulmonary resistance, pulmonary hypertension, it will limit the shunt and potentially for years, it can control symptoms of heart failure, although eventually, uh patients may develop what's called Eisenmanger syndrome, which is right to left shunting uh from a fixed uh uh pulmonary vascular bed with severe pulmonary hypertension. So, as Laura said, the, the question is about surgery here, right? I mean, that's all background. And so, there have been many papers as were described in previous talks in the last 10 to 15 years, describing an evolution about outcomes uh that has informed uh the contemporary approaches. Uh, I picked, uh, this paper from, uh, Greenberg and the Junior Pediatrics because it's multi-center. Using the FIS database, these are administrative data, so they have some limitations. But I do think that the uh individual center variation is so um important to understanding the data that really to understand the landscape, you need multi-center data on this. And it's very clear that there's a trend in the increasing number of cardiac surgeries being offered. Uh, the top line is for trisomy 18. Uh, and the bottom line is for trisomy 13. And so, um, trends that have been already discussed, uh, in the, uh, dance talk, uh, but this is a graphical description of that in the US. There were 74 centers involved in this data set that had offered cardiac surgery, um, As far as the outcomes, uh, in this large multicenter study, again, to point out, and this was, um, discussed earlier, even in this most contemporary, uh, data set, um, it's still a minority of patients who are undergoing surgery. So 12% with trisomy 13 and 17% with trisomy 18. I, I think that if you, uh, repeated the study with data between 2020 and now, uh, we would definitely see an inflection point and we've seen that in our center, uh, uh, as well, but this is the national trend. Um, in this study, the inpatient operative survival to discharge was over 90% for both trisomy 13 and 18. Um, because it's an administrative database, it's a little challenging to understand all the details. About indication and case selection, which are critically important to interpreting those outcomes. Um, but interestingly, uh, the, the table shows that a variety of operations were performed, and I'm not gonna go through everything. The most frequent are, again, left to right shunts, but there is a small number of patients who underwent, uh, more complex interventions. Um, and I note that as an observation, though it's a little um hard to interpret, um, if there were unique circumstances, uh, for those patients who underwent, um, one of the single ventricle palliations, for example. So, I think all of this has culminated in a really nice manuscript that was published last year uh through the American Association of Thoracic Surgery. Um. Uh, I will also put a plug for folks to read this, uh, manuscript if they are able to, to really get a understanding of where the centers that focus on this care are right now. You know, I would say our center, um, uh, in the last 5 years, uh, even before this was published, has had a very, very similar approach, and I think Uh, I'll focus on the recommendations from the paper, but it does very much parallel what we've been doing. Uh, in the manuscript, they divide up congenital heart disease as mild, moderate, and severe in order to, uh, help with risk stratification and providing these recommendations. And I'm gonna actually go through a few of them because I think that they're good discussion points and might generate uh uh some dialogue as part of the seminar today. So, uh the first uh recommendation I'll highlight is that infants with mild to moderate complexity confined to the hospital, uh, cardiac surgery is reasonable if the hemodynamic consequence of the CHD prohibits discharge. So, uh, by far the most common situation will be the baby with left to right shunt. Who um is clearly in congestive heart failure. As assessed by chest X-ray, respiratory rate, need for support, uh, BNP, um, those patients who are clearly symptomatic to, uh, a VSD, And removing that left and right shunt might improve their respiratory status and allow them to uh progress, hopefully, uh, through the hospitalization and hopefully to home. Uh, that's the example of, uh, where this would be uh reasonable according to the guidelines and is probably the most um common example, uh, in the community right now of where surgery uh can be performed with relatively low risk, uh, and anticipated. Uh, good results. Um, in contrast, infants with severe complexity and single ventricle, the recommendation is that it might be reasonable to not offer cardiac surgery. Why is that the case? Um, what we know about the anticipated early operative and late risks primarily related to pulmonary vascular disease and respiratory function. Um, as well as the limited, uh, data that have been published about outcomes in this patient population would indicate that the outcome is likely to be poor. Um, and, uh, family certainly need to understand that, and most are not interested in, uh, pursuing a, a poor outcome that is concerning for both short-term and long-term, um, quality of life and survival. So, uh, that's the more complex disease recommendation. Those with mild to moderate complexity who are at home or need recurrent admissions, timely elective cardiac repair is reasonable. I would say it's the same logic that justifies uh intervention on children with either left to right shunt or potentially um cases like tetrology or forms of double outlet right ventricle uh who have two ventricles but have obstructed pulmonary blood flow and some degree of desaturation from that. Um, these are patients who, in the absence of their trisomy would be at home and would come in for cardiac surgery, and those are, um, patients who, uh, are reasonable candidates for surgery through the guideline and are certainly, those are the types of patients that we have operated on in the last few years. Um, I'll be interested to see what Laura has to say about this because I think the interplay between the extra cardiac defects with oesophageal atresia being one example, and the repair of mild to moderate complexity CHD um does cut both way in that they each present risk to each other. Uh, these guidelines recommend that cardiac surgery involving cardiopulmonary bypass might be considered once the other defects are adequately addressed. You know, one editorial to that is PDAs are in today's world, mostly easy to address through interventional cardiac catheterization. Uh, in the trisomy, uh, babies, sometimes they're a little bit big and we still do, uh, have to look towards ductal ligation or surgical closure, uh, in some based on the Ductal morphology, but most can be closed in the cath lab to address that shunt, um, prior to, um, a, a surgery, uh, that can be delayed a little bit for extra cardiac defects. Um, and those who are ventilator dependent, the repair of mild to moderate complexity may be considered if the severity of respiratory disease is not prohibitive. Long-term tracheostomy, uh, should be discussed as a possibility. So I mentioned earlier that, um, The airway, uh, uh, cardiac, uh, interplay is complex and, um, sometimes we find that relieving the shunt isn't enough, uh, to, um, avoid the need for mechanical ventilation. And what's important is that before we entertain the surgery, that the family and the team are aligned on those expectations, uh, And discuss what would be planned if we're not able uh to uh sufficiently improve the respiratory status uh with cardiac surgery. Um, because if you don't do that upfront, then you're stuck. Uh Because families and children with trisomy 13 and 18 are prone to develop early pulmonary hypertension. Early cardiac surgery is reasonable in mild to moderate complex disease, and this is driven, uh, as I mentioned earlier, by the observation that the pulmonary hypertension is early in onset. and becomes irreversible early onset. Uh, the cardiac world has clear guidelines about, uh, risk stratification of, uh, open heart surgery, uh, in the setting of elevated pulmonary resistance and pulmonary hypertension, and that there are levels where the outcomes are very poor. Um, and so, um, You know, if there's an opportunity to close these at an earlier time point and if the family requests that, Um, uh, these recommendations advocate for timely means, uh, as, as soon as, uh, the risk is acceptable. Uh, I'll highlight that there are, you know, Almost all of the literature on the topic is cardiac surgery. I actually struggled quite a bit to find a large series on interventional cath procedures. But over the last few years, um, we have opted for more of this, uh, with all three of these procedures having been performed at Cincinnati Children's. Uh, on the left is closure of a PDA uh by uh a ductal occlusion device. This is mainstream care in the NICU and the interventional cath lab. Um, It's a little bit different in trisomy 13 and 18 because the duct morphology can be a little different, but as long as the, the nature of the PDA allows, uh, we can avoid cardiopulmonary bypass and close the PDA through a device. Importantly, uh, assessing the pulmonary vascular resistance and pulmonary hypertension before doing that. Um, the middle example is a case where pulmonary blood flow is obstructed by a small hypoplastic pulmonary artery, um, This is the best figure I had. It probably more commonly it's performed in, uh, trice excuse me, in tetrology of flow, uh, in this patient population, uh, when they need just a little bit of extra blood flow by keeping the duct open, and that can uh buy time uh when the family would like for a more definitive, uh, intervention at a later time point. Um, and that, um, ductal stenting tool is really, um, evolved in the last 10 years to be used widely for various forms of congenital heart disease with reduced pulmonary blood flow. And then the last figure here, illustration here, uh, if you see these two little gray footballs out in the branch of pulmonary arteries, this is the, the newest uh. Uh, intervention, uh, for left to right shunts, uh, in our, in our, uh, clinical environment, which is, which are called pulmonary flow restrictors, and these were designed as vascular plugs to be used in interventional radiology, but you can poke little holes in the End of these flow restrictors to allow just the right amount of blood flow through and they can be placed percutaneously in the cath lab to reduce the left to right symptoms. And in general, these are used as a palliative step, um, Historically, a pulmonary band might have been used, but I think um we are moving towards more of these pulmonary flow restrictors as a temporary step to help uh control heart failure symptoms, help a baby to grow, and then to get to a lower risk for Uh, uh, cardiac surgery. All of this provided that, that the, the family is, uh, guiding us with their wishes. So, um, our approach is very similar to, uh, the, uh, AATS paper with individualizing decision making related to the variables listed, uh, favoring, uh, repair for, uh, A low complexity lesions which normalizes physiology and And simplifies care. Um, we offer catheter-based interventions, uh, when appropriate based on the clinical problem. Um, and then when second, uh, opinions come through, uh, particularly postnatally, uh, one thing that wasn't Clearly mentioned in the guidelines papers, but, uh, we typically ask for a formal airway evaluation to make sure we uh optimally understand um the likelihood that heart surgery is gonna achieve the goals that the family hopes for. And then, uh, we've had a couple of patients who have, um, Had hepatoblastoma and so we typically would screen uh through a referring center to make sure that that is not a subclinical uh problem that might come up in the middle of cardiac care. And so since 2019, we've done 17 um. Index, uh, uh, cardiopulmonary bypass, uh, procedures, um, mostly in simple shunts, but, uh, 6 of these were tetrology and double outlet right ventricle. And the operative survival at our center is right in the range of the Balt Center report at 94%. So, um, in conclusions, uh, the cardiac disease is clinically important. Uh, the intervention landscape is rapidly changing with more frequent surgery and improved outcomes in the mild to moderate disease range. Um, outcomes in the severe congenital heart disease range remain challenging, uh, and individualized approach is needed for each child and family. Thank you for your attention. Thanks, Doctor Sonoda. Um, I would love to have you do a little bit more of your editorial on that excellent survival that, um, you've achieved at Cincinnati Children's and also the other pretty good over 90% survival for the cases that are selected. So, do you think it's really all selection? No, I don't think it's all selection. I do think that selection is important, case selection. I mean, it's important for Every procedure. Right, uh, so case selection is important, but I also think that As you do more, you learn more. You know, you, you learn more about how the unique considerations of caring for uh these patients in the ICU in the postoperative phase in particular, I think is the important element and I'm a fetal cardiologist. I'm not a cardiac intensivist, so I'll be careful in getting too far into cardiac intensive care, but I do think that um we've learned some how to take care of these kids, uh but A large portion of it is careful case selection. And, uh, understanding, um, not just the cardiac disease, but the status of the pulmonary vascular bed, the status of the airway, in particular, um, I think those things, um, are critically important. We had another question, uh, in the chat. Um, how does your team, uh, navigate understanding each individual patient's pulmonary hypertension, um, and when that patient, uh, is likely to require a surgical intervention? Yeah, uh. Excellent question. Um, I would say that We use clinical and laboratory and imaging information. Uh As the first line, which is I'm sure is what your center does. Um, and if the heart is big and the lungs are flooded and the BMP is high, Then that's easy. We don't do a cath. We would entertain closing the hole. Um, and there's, and there are quite a few of those patients. Um, the, uh, when Um, Those pieces and, and if the heart is big on echo, um, and there, there will never be a pressure gradient when the VST is large and non-restrictive, so that piece of information, we, we know this RV will always be systemic in that setting. So, you know, how do you assess the quantity of a shunt? So, if all those things are there, then we don't need a cath. When the the puzzle doesn't fit together. The LV is small. The baby's not breathing fast, then we would do a cath. Hopefully Without going into all the details, that's uh clear and then if the patient doesn't uh convalesce as anticipated and we see signs of pulmonary hypertension, uh, on an echo, we would certainly recath post-procedure and consider, uh, vasodilators to help get through that. Great. I think there's a couple other questions we'll just have you uh answer offline a little bit. Sounds great thank you.