Chapters Transcript Video Eisenmenger Syndrome & Pulmonary Hypertension in Congenital Heart Disease Dr. Alexander Ellis describes the origin of Eisenmenger syndrome and disease specific therapies for congenital heart patients. Welcome everybody. Uh It's, it's a privilege to be here uh with Kim's parents and to be giving the first annual Kim starring memorial lecture in congenital heart disease. Um Many of you guys have met Kim uh in, in the past I have taken care of. Is it cheering the privilege to have cared for her? Uh During during her card, he faded out a little bit. Talk a little bit about the specifically with e difference there. Um And, and then talk a little bit about the, the the treatment modalities that we're using for that. But first a little bit about Kim's life and for those of you here in the audience, um her parents just gave me another picture of her, but we have a few pictures here on the screen. Um Kim uh was a vibrant individual. She never let congenital heart disease hold her back. She uh has uh she had a fantastic life where she took, she always told me about her fantastic vacations where she would go on, on RV, trips down to, to Memphis and bring me back barbecue sauce or the mountains of North Carolina or even to Mount Washington. Uh her husband Mike unfortunately is, is sick today. So he's not here. But um I would always joke with Mike that he took her to the top of Mount Washington if you have congenital heart disease and, and Eisenmenger syndrome, altitude is not your friend as we will talk about. Um But here guys, I have proof that you too, both took Kim to altitude as well. Um So it wasn't just uh it wasn't just Mike trying to kill her. Y'all tried to do it too. Um So, uh there does. Yes, I'm sure that's true. So, so, uh again, in, in, in honor of Kim, I have uh made her uh memorial lecture blue because for those of you who know Kim a sad of 75% was a good day for her. So let's briefly talk about Kim. Um Kim was born with teter of low with pulmonary atresia and a very discontinuous uh left pulmonary artery that was fed exclusively by small little collaterals. Now, I'm no Picasso. Um But I'm happy for uh for Doctor Adler to take me to the uh to, to the Van Gogh Show or the Picasso Show later this summer um to improve my artwork. But, but here's what I've been able to diagram. Uh she, she had a tet of that was palliated with what's called a Waterston stunt. And hopefully, uh well, my pointer is not working. Um But hopefully you guys can see that that her right pulmonary artery is directly surgically anastomosed to her ascending order. So that was essentially Kim's only source of pulmonary blood flow. Uh And that's called a Waterston Shun. And we, we no longer do that and haven't for, for decades. But uh but that is uh was what Kim had. She developed Eisenman physiology. Uh And we'll, we'll talk more about what that means later. But, but essentially her shunt lesion was reversed and she had exclusively right to left flow at her ventricular septal defect. Uh A as that was the only means of egress from her right ventricle. And so she was a complete mixer, her, her oxygenated and deoxygenated blood uh mixed completely at the VSD level and into the aorta. She actually is I don't have on here, was also born with a double aortic arch as her parents will remember and had that repaired uh in her first year of life as well. And part and parcel of that is that her ay aorta was quite large up to uh six centimeters in diameter. Um Some of that was, was because of uh of the double arch repair as well and, and how that physiology worked. Um But her, her right pulmonary narrowed a little bit as it came off the aorta, but she had relatively good blood flow to that single lung. Um But that single lung was not great. Uh And for those of you who remember her in the IC U, she did have significant restrictive lung disease and hypercarbia. So it caused a lot of pulmon invasive constriction. And so again, SATS of 70 to 75 were about as good as she would get. And she had secondary erythrocytosis due to that and usually her hemoglobins were 17 to, to 18 at least. Um But this is not how we choose to remember Kim. This is how we choose to remember Kim and she would find it wickedly funny. I'm showing a black and white picture so you can't tell that she was blue. Uh So what we hope to talk about today in Kim's memorial or annual memorial lecture uh is congenital heart disease, not coronary heart disease. As, as this building tends to use that abbreviation more for coronary heart disease, but congenital heart disease and pulmonary arterial hypertension. The origins prevalence, talk about Eisenmenger syndrome a little bit of how it differs from Eisenmenger physiology and its multisystem effects. Talk about some general pulmonary arterial hypertension management specifically with regards to congeal heart disease and some of the disease specific therapies. So before we get there, uh for those of you who know me, I like medical history and I'd like to talk a little bit about how we got to this point of having frankly the privilege to take care of adults uh who have survived congenital heart disease in childhood. And for those of you who don't know me as, as Doctor Tarea said in his kind introduction, I am a pediatric cardiologist. I did both internal medicine and pediatrics and then did a ps cardiology fellowship and did some adult adult congenital heart disease training. After that, that is how a lot of us who take care of adults with congenital heart disease trained but not all. Uh there are a growing number of, of uh of adult cardiologists who have gone down the congenital heart disease training pathway. And in fact, some of the giants in the field including Jane Somerville, Gary Webb, who I trained under Joe Perloff at UCL A. Those are all adult cardiologists who became interested in taking care of adults with congenital heart disease in the seventies and eighties. Um And they uh along with Maude Abbott A a as you'll hear from from Montreal, uh those uh those pioneers really are the reason that we have this success story today. So here's some data from Canada looking back to 1985 when doctor Adler and I were in in middle school together and, and all the way through the early two thousands. When we're seeing both in the gray lines and in the black lines, the prevalence of uh of congenital heart disease. The top graph there is all congenital heart disease. The bottom is the severe forms, the more uh cytic forms, whether they be single ventricle physiology, truncus um and some forms of tar the as you can see the prevalence is increasing both in Children and adults. Um And what you'll see later is that the number of adults now living with congenital heart disease exceeds the number of Children. So there are about 900,000 Children uh 0 to, to 21 of course, uh with congenital heart disease that has been eclipsed about six years ago by the number of surviving adults with congenital heart disease that are now more than 1.5 million and barring some different pandemic. Uh We expect this to continue. So again, the number of people in this building or who are eligible to be hospitalized in this building will exceed the number of people who with congenital heart disease, who can be in my building across the way. So this is a, this is a problem facing all of us and uh and and I'm glad that we're here to talk about it. Um But, but the bottom graph is also telling him that severe forms of congenital heart disease are now becoming more prevalent in the adult than in kids. So we have to become better at taking care of these uh of this special population. So, congenital heart disease affects 1% of all babies born. So it is uh Jerry Lewis and his telethon would be very disappointed to hear that. Actually, congenital heart disease is the most common birth defect if you want to call it that um it is, it affects 1% of all babies born. And this, by the way is not including bicuspid valves or, or uh microvalve prolapse, et cetera. This is um no offense to my father who was born with a bicuspid valve and loves to tell his uh uh his friends that he was born with what his son treats. No, no, no, dad, bicuspid valves are not interesting to us. Uh They, they are not a real form of congenital heart disease for this data. Um but medical and, and surgical progress, imaging such as uh IHS and what doctor Basin does um surgical techniques calf procedures. Uh EP procedures, all of these have allowed uh congenital heart disease patients to, to survive into uh into adulthood, but it varies depending on the lesion. So as you can see in the graph, uh more straightforward lesions such as uh ATRIO seal defects, ation of the aorta V SDS, even some forms of tetra of flow with pulmonary stenosis different than teter of flow with pulmonary Traa. Um have much better survival. Um uh even in the 19 eighties and nineties when this data was collected as opposed to cytic defects like what Kim had or our single ventricle patients. Uh So most of these procedures are palliative. They're not curative. We're not good at curing people except for our EP colleagues with WPW. We're really not good uh at fixing things entirely. We're better at making things work for as well as they can for as long as they can. So these patients will require ongoing surveillance, they will require ongoing medical management and interventions. Um uh And that's why we're all here. So, where did they come from? Well, uh this is where it all started. Uh And again, I love medical history. So we're gonna talk about Doctor Lila High from the University of Minnesota. Walt was the uh as you can see, he was a medical school graduate. Yes. And he performed the first open heart surgical procedure in 1954. So it's remarkable to think that uh that only 20 years later, Kim was able to benefit from, from this sort of development. Um And if she'd been born in a different era, she would not have been able to have had the rich life that she had. How did he do it? He used control cross circulation, which to my knowledge is the only procedure that has a potential 200% mortality, I guess, except if I were doing cardiac surgery, then it would be the patients and probably me. Um but controlled cross circulation is where the parent is the eye and the ventilator and the pump. So here, clearly, it's the father, we can tell um the father's femoral artery and vein are cannulated. They do go through a pump. Um But the, the father is the oxygenator. Uh and then the, the, the child is can um in, in the method that is still fairly similar to how we do things today. Um And this is a picture from the actual operating theaters as they called it. Um, back then with the uh child being in the center and the parent being off to the side. It's incredible that, uh that we were able to, to do this in the 19 fifties, I don't think institutional review committees or I RBS now would, would permit such things. Um uh it, it, it would take a whole lot of, of heavy lifting to make that happen. Um But we are all uh in, in debt to, to these pioneers and to these pioneers from congenital heart disease. So, Helen Tausig is considered one of the grandmothers of pediatric cardiology from the Johns Hopkins University. Uh She really is uh the founding mother along as you'll hear in a minute with Maude Abbott from uh from, from mcgill in Montreal. She is the, the, one of the pioneers of congenital heart disease uh therapies and pediatric cardiology. She partnered with Alfred Blalock who was just a surgeon. They didn't have cardiac surgeons um in the 19 forties in Hopkins. Um and the lab director, Vivian Thomas, uh who really is the one who made sure that uh that this procedure would work. He really was the technical expertise and, and the genius behind the scenes to make this work. And so, what is this the classic Blalock tosh? And for those of you who have seen some of my patients um like like doctor jets and others, you know that classic Blalock shunts are different um in compared to what we do in the modern era, which is the modified Blalock haig shun, the classic BT shunt uh has the same complications as say a subclavian flat prepare for a cot. We take intentionally the left subclavian artery or the right. And in some of my patients like one, that one gentle doctor gentler partners is going to ablate soon. Both subclavian are turned down to the pulmonary arteries as a form of systemic to pulmonary artery shunt. So this provides blood flow, oxygenated blood flow to the lungs in patients who have too little pulmonary blood flow. So this is what uh Helen Tausig envisioned uh and uh Vivian Thomas perfected in the lab in the dog lab and Arthur Blaylock uh performed for the first time in 1947. So this is a newspaper clipping from the American Weekly from Baltimore in 1947 saving our doomed blue babies. Um with again the, the classic Blalock to shunt. So I thought this was pretty incredible that we were able to, to find this. Uh the the reporters uh did a reasonably good job at diagramming things although apparently this patient only has one lung and no VSD or, or um uh and certainly they didn't get to correct which is what these, these patients had uh initially. But the, the, the development of surgical technology uh to treat cyanosis uh was a watershed moment for congenital heart disease. So, what are some of the forms of shunts that we have? Well, as we mentioned, Kim has a Waterston Shunt. Waterston and pots shunts are two of the initial uh surgical palliation for congenital heart disease that came after the classic BT shunt as we've just talked about. So, Waterston Shunt, I don't think anyone uh on the on the call can see, but for those in the audience, the back wall of the aorta is ANAs tomos to the front wall of the right pulmonary, of course, the RP A goes directly behind the AORTA in most patients. Um uh So, and, and Kim, it was a little challenging because she had a double arch but, but essentially, that's what they did. They announced the most the back wall of the Ace in the order to the front wall of the right pulmonary artery. A pot shunt is the reverse. It is the back wall of the left pulmonary artery to the front wall of the ace. The order neither of these are done anymore because they distort the pulmonary artery architecture. And because as you remember from Poo's Law and in physics or I try and block that out, but there's very, because there's no link to these, the resistance across these shunts is very low. So the development of pulmonary hypertension is, is very rapid. So, so remember, it's I I it's radius to the fourth power. So it really depends on how big you make these divided by length without any exponential increase. So, so length is important, but radius is even more important. Um And it was very difficult to get the right in the operating room. Um And of course, there was no length. So um uh so, so there was the, the, the resistance ended up being very little across those. And so they all developed pulmonary hypertension very quickly. A central shunt is something that we still do. Uh That is uh it can be done a variety of ways. But, but from the aorta over to one or both of the pulmonary arteries. So that gives you a little bit of history, not just kim surgical history, but but for shunt lesions, which is germane to this talk. Um uh So then we'll once again come back to this population. How did it grow once the advent of this technology took hold? So in the 19 sixties, about 50% of, I'm sorry, about 35% of, of uh our patients with congenital heart disease died in childhood, 50%. So a full 85% died in their first year. So we weren't very good at taking care of, of Children with congenital heart disease. In the 19 sixties, only 15% survived to adulthood. And most of those were probably some smaller pdas A sds and some teter technology patients who really didn't have that much pulmonary stenosis. It's like goldilocks. I had just enough not to develop significant uh pulmonary hypertension, but not too much to make them blue. Look at how that changed over 50 years. So in 2010, which is the last year, we have good data for thanks to the pandemic, 85% of the same patient population was now surviving to age 21. If that's not a wake-up call for our profession, both pediatric and adult cardiologist. I don't know what is this population is coming. In fact, they're already here. As we said, we already have 1.5 million adults who are living with congenital heart disease and I'll continue to Trump at this. There are more adults with CHD now than there are kids. Many of these will develop pulmonary hypertension um even from simple lesions. Uh But, but as you'll see up to about 10% of patients who even have had good treatment, who have had good surgery, who've had good surveillance through childhood can develop pulmonary hypertension as an adult and they get admitted to the hospital and it's not often CHKD. So here's data from uh from Doctor Tare's former institution, but deep I think that you were, you were not quite there in 1997. Uh But this is from uh from uh the, the robust ach D clinic that that exists at the Mayo. Uh And, and you'll see that, of course, the numbers are increasing across all uh age groups, but especially that 30 year old group uh and that the greater then sign should be in front of the 30. Um But I suppose they do things differently in Minnesota, the greater than 30 age group, you look even in the late nineties had eclipsed the other two age groups for hospital admissions from 2014. Looking at pool data from, from uh from medic C MS data. Um Doctor o'leary from uh published in Jama, uh the same sort of trend you can see the hospitalizations across the board were increasing. But once we started to get into the two thousands, the pediatric hospitalizations leveled off but not the adult hospitalizations, those have been steadily increasing. So this is an iceberg effect. We know the top part, we know what we can see. We know what is coming into the to, to the er s and, and, and to uh to our wards now. But I'm here to tell you there are many more of them that we're not seeing. I get a call at least once a week from, from an office somewhere, a primary care office, an ob office where they actually examine the patient and see a scar on their chest um rather than just a a below the chest examination um uh from, from urgent cares, from lots of places saying I have somebody here who's had surgery when they were a kid. They don't know what they've had done and, and, and help, they've got a murmur, they're having palpitations, they're blue, whatever it may be, there are a lot of them, they do have ongoing cardiac uh and other noncardiac medical problems. They're coming to our adult IC us, our adult er s labor and delivery units, offices and cardiology wards and they need both general cardiology care and other subspecialty care and they're not going away. So, let's pivot now and talk about pulmonary hypertension as it relates to patients with congenital heart disease. So, how do we classify this uh adult congenital heart disease uh with uh or pulmonary hypertension rather than adult congenital heart disease can be both precapillary or postcapillary. So, uh is it, is it pulmonary arterial or pulmonary venous? It is a general truism that lesions with more copious flow uh or further downstream lesions, what we'll call post tricuspid left to right shunts as opposed to pre tricuspid left to right. Shunts are more likely to cause pulmonary hypertension and differentiating the ideology does impact management and potentially the ability to close residual shunt lesions and make things better. Um The uh And again, we have guidelines now, not just uh recognition of this problem, but we have guidelines from both the American Heart Association, American College of Cardiology and the European Society of Cardiology and now some ACH D board certification to help with this process. A and a lot of that is because most physicians get very little, most adult physicians get very little exposure to congenital heart disease and their training. And I hope that this process will, uh, will, will improve that. I have actually been, uh, even though I am board certified, I've been a vocal opponent to doing that. I think that all we're doing is making our club more exclusive and we don't need to do that. What we really need to be doing is taking interested adult cardiologists and helping to provide educational resources, conferences, online and person materials. Um and, and other short term um uh additional fellowships or other short term training programs uh are, are mentorships and trying to build expertise in the community and in academia, not just uh just have people who have different letters after their name or board certifications because that I think doesn't serve this patient population well, um uh in, in my view, a rising tide floats all boats as opposed to being more exclusive. Um But that's uh not how all the the academic centers operate. Um But, but expert care is necessary for this population. So, shunt lesions like what Kim had uh are the most common cause of pre capillary, pulmonary arterial hypertension. So whether it's an A SD, which here we've, we've diagrammed with bidirectional flow, of course, usually and hopefully it is all left to right or, or oxygenated to deoxygenated side L A to RAV SDS. Uh That that again, due to the higher pressure load or, or pressure ahead of the ventricle typically are left to right. But in Kim's case, that was not true. Um or PDAs, um both of these can cause um can can cause uh excessive pulmonary blood flow leading to increased pulmonary vascular resistance and eventually reversal of shunt flow. So, up to half of patients with untreated congenital heart disease, uh lesions will progress to Eisenmenger syndrome where we actually get complete flow reversal of the shunt lesion if untreated. Uh And it's not surprising, some of the the symptoms would be increasing dyspnea, declining exercise capacity in adulthood. Um And when you take them to the lab, progressive increase in pulmono vascular resistance. So uh I I don't expect anyone but doctor basin to me memorize this table and there will be a quiz for him when we leave. But the nice classification, it's not just nice, it's nice. Um Or the World Health Organization classification of pulmonary hypertension um is here, I'm just gonna direct your attention to this part of group one which is heart disease. Uh pulmonary arterial hypertension associated with heart disease and the pulmonary hypertension due to left heart disease. Uh because we see both in, in our CHD patients and both were at play for Kim. The definitions are similar, you have to have a mean pulmonary artery pressure of 25 or more and, and others and look for this definition potentially to change in the next few years, this, they may start to move this down to a mean P A pressure of 20 there is movement in the field to do that. But you also have to have a wedge pressure for our patients of less than 15. Um unless you're looking at the group two and a a um P vascular resistance of more than three wood units, um indexed to body surface area. So for our group, one patients due to large left to right shunts, these are typically post tricuspid left to right shunts. So things that occur after the tricuspid valve V SDS, PDAs and A V canal. Uh I in, in this case, is, is really um both a pre tricuspid and, and uh post tricuspid shunt, uh aorto pulmonary windows, those sorts of things. Um Ron arteriosus can all lead to significant left to right shunt that again, if left untreated is going to increase your pulmono vascular uh resistance if you however, ignore pre tricuspid left to right shunts. And we've seen this unfortunately twice in the last couple of years at CHKD and A SD that, that went undetected. Um not just from from international adoptees. I've had two of those in my clinic recently, um who who have been unrepaired and, and have significant pulmonary hypertension due to an A SD. Um but, but even from, from people who are theoretically getting good uh good medical care in childhood, um partial anomalous pulmonary venous return that we see quite commonly and, and Dr Basin sees on his CTS, this can lead to uh to pulmonary artery hypertension. Um And, and that potentially can be reversible if treated medically ahead of time and then surgically with, with um re Anestis of the pulmonary vein to the left atrium. So, uh the, the conventional wisdom is that a SDS before age 10, generally, you have a golden opportunity if they're hemodynamically significant to repair those. Um But once you start getting into your teenage years, it becomes a much more fraught decision about what to do and how to manage them. Um especially if you have things like Trisomy 21 that by itself even in adulthood is an independent risk factor for developing pulmonary hypertension. Um Single ventricle patients are a completely different uh breed. Um And if they develop pulmonary hypertension, which they certainly can uh that makes uh passive pulmonary blood flow even more challenging. Um And they have an exceedingly high mortality from that. Um But the definition would be a transpulmonary gradient, meaning a mean P A pressure minus the wedge pressure of more than six. Once you start getting transmitted gradients, normal is, is, is four or less. Once we start getting up to six, that's really a problem for this group. Um And, and left heart obstructive lesions uh which uh you guys are much more familiar with uh back pressure from uh from high LVEDP or high left atrial pressures. From a variety of reasons whether it's diastolic dysfunction, mitral stenosis, pulmonary vein stenosis, those are all, as we said, group two. So just showing again the, the, the different definitions, the group two of course, have a higher wedge pressure, a higher left atrial pressure um compared to the group ones. So uh I knew Doctor Adler would be here and I appreciate that. So I put some Mullins diagram, some cat diagrams in here because he likes these. So an example of precapillary, pulmonary arterial hypertension is here where you have, excuse me, I mean P A pressure of 50 but a wedge pressure of 10 post capillary, uh pulmonary hypertension, of course, whether it's due to mit stenosis or high LVEDP, the way I've diagrammed it here, it can't be um uh it can't be pulmonary vein stenosis. Um uh So those would be examples of the uh of the hemodynamics. Uh And in the absence of microvalve disease, we assume that pulmonary artery wedge pressure um and LVEDP are generally the same but not always. Of course, there are, those are some of the exceptions down at the bottom of the screen which are common in our adult patients, especially a fib and large left atrial diameters which our ep colleagues will see frequently. So why do we care so much about pul artery hypertension? We've said that it's um that, that it complicates the management of a lot of our adults with congenital heart disease. Uh But unfortunately, the mortality and resource use are much higher in this population than the same people with the same lesions who don't have pulmonary hypertension. So, a tar patient who has ph uh is is much harder to manage and much more expensive to manage than those who do not. So, here's, here's a study from about 10 years ago from, from Canada, um uh about 38,000 adults with congenital heart disease from, from Quebec. And they have a very uh robust registry system in Canada. Um and a very robust congenital heart disease program in Canada. They're looking at uh at almost 40,000 adults, about 6% of those had pulmonary hypertension. So uh I did some additional math. That's 6% is just one in 17, but it sounds great to say that. So, one in every 17 patients with congenital heart disease has significant pulmonary hypertension. They had a two times higher rate of mortality compared to, again, diagnosis, matched controls who didn't have congenital heart disease. Their morbidity was three times higher and they were, they had three times more um or three times uh uh longer hospital stays or more hospital days than those who did not. So, there's uh the consequence of having congenital heart disease or PAH associated with congenital heart disease is, is significant. So, let's pivot to the specific form that, that uh that we're here to talk about Eisenmenger Syndrome. Uh And, and I'll take a moment to, to talk about the difference between Eisenmenger syndrome and Eisenmenger physiology. So, Eisenmenger's syndrome is where you have, for example, an untreated VSD where you have the reversal of shot flow because it is untreated and you develop pulmonary obstructive vas, pulmonary vascular obstructive disease. Eisenmenger physiology is what Kim had. She was techology of flow with pulmonary Trisa. She didn't have any, any outflow from her, her right ventricle. So she always had obligate right to left flow across her VSD. But she developed high pulmonary vascular uh resistance because of the increased flow from her RP A being anastomose directly to her, her aorta. So she had the same complications. It's semantics really, but she didn't have the reversal of shunt flow uh because she anatomically couldn't. But where did it come from again? I like medical history. So, uh so uh Victor Eisen Eisenman, excuse me, was an Austrian physician uh who lived in the late 18 hundreds into the early 19 hundreds. And he is the one who first recognized uh generally um at this time, they were, they were recognizing them postmortem. But he actually recognized this patient and the physiology premortem. Um back in 18 97 it was a 32 year old who had an unrepaired VSD who he had followed. Uh and he recognized that he developed a lot of the complications that we now see with Eisenmenger syndrome. Uh and he watched this in VIVO and then, then he did an autopsy after the patient died. Um, he's actually more uh notable for being, uh Franz Ferdinand's uh personal physician. If he'd only helped him not get assassinated, we might not have had World War One. so, uh Victor, um, could have been a little bit better at trauma surgery but was really good at, uh, at cardiology. So, unfortunately, we did have World War One. So that's Victor, uh Eisenberg or Eisen Manger, excuse me on the left and Paul Wood is on the right. Uh a British uh cardiologist and one of the fathers of pulmonary hypertension in general. Um uh of course, of the Wood Unit Fame. Um And then Maude Abbott is listed down here. So Paul Wood and Maude Abbott really recognized that the a and described more completely the, the syndrome and the physiology and its multisystem effects. Um When she was, she is, as I said, one of the grandmothers of, of pediatric cardiology from mcgill in Montreal. Um And here are just some interesting um uh stamps, one from Indonesia, one from Cameroon. Um and a a and I thought it was great in Cameroon. Uh just like the one in Indonesia, you apparently only have a left pulmonary artery, no one has right pulmonary arteries uh and no one has V sds. Um but uh the artist made an effort. So with Eisen Minger, um as that top diagram will show you'll have some shunt le excuse me, with an increased amount of pulmonary blood flow or QP that will eventually lead to higher pulmonary artery pressures that develops higher pulmonary vascular resistance, resulting in bidirectional flow across that defect with further flow and further increase in pressure. Your shunt lesion permanently reverses. And now you only have right to left or deoxygenated to oxygenated flow a across the shunt lesion leading to very severe SSIs. And, and as you can see in the right diagram, the top part portion, your pulmonary arterial walls become much more thickened, your pulmonary arteries become uh thickened and dilated and more muscular. Um And uh and this becomes a permanent effect. So, again, over time, you're red to blue, your left to right shunts uh reverse direction and they become right to left or blue to red. There is multisystem involvement with this which we'll get to in one moment. Um Actually, I'm gonna go to that right now. Um So what is the multisystem involvement? And I cannot take credit for this. Uh This slide comes from Mike Eggert. Um and some of his uh so some of his talks um but Mike didn't draw this either. Uh he'd be a better artist. Um but there are many additional noncardiac effects of pulmonary hypertension in general. But Eisenmenger's in particular, it is common to have, I'll start down with the legs because I'm closer to those Levita reticularis and Kim's parents will remember that Kim had this in abundance. It is common to have some peripheral edema. It's common to have gout. Why would you get gout because of red blood cell breakdown products? These are all patients who have secondary erythrocytosis, they make more hemoglobin, they break down uh more red cells and have hemoglobin breakdown products including uric acid. Uh So it's common for our single ventricle patients, our fontan patients and uh pulmonary hypertension patients to have more R BC degradation products including uric acid in their bloodstream. So, I've still been very good at Ayol and Co um and you'll see that uh on the cardiology wards, they will have hyperviscosity syndrome uh or symptoms rather. So they'll have some leg cramps, they'll have headaches. Um And I'll take one moment to say that that pulmonary hypertension patients in, in adults in adulthood and especially Eisenman because of the shunt reversal, they're at risk for cerebral abscesses. They're at risk for, for uh for uh for endocarditis, but very much at risk for cerebral abscesses. We've had two in this building in the 17 years that I've been here um again, because it doesn't go through the lungs to, to filter out some of the um uh some of the bacteria uh that, that would otherwise end up there. Um uh You do get uh cerebral ayes. So headaches or change in sensorium in these pulmonary hypertension patients associated with heart disease. You should definitely consider uh cerebral ayes and send them for some sort of cerebral imaging. Again, it's not theoretical. We've had two in the last 17 years here. Um But high viscosity can also lead to headaches, cerebral sludging um change in behavior. Um The cardiac physical exam, of course, you'll have an increased second heart sound, um the intensity but a single second heart sound. Um oftentimes your diastolic murmur of pulmonary efficiency will be of much higher pitched uh but not holo diastolic because your, your, your EDP of the RV is gonna be higher. Um So generally it's a shorter uh murmur of pulmonary in efficiency but higher pitched. Um and you'll have, excuse me, an RV lift, what's quite noticeable. And again, Kim's parents will, will, will attest to this is the clubbing or the, the, the uh changes in your digits that you start to see your um from the SSIs. So this, this I put on for those uh who who love physical exam. So normally you'll have this diamond sign of your fingernails. If you start, if you hold your fingernails up uh together and look through, you'll see this, this area of, of light coming between them, this diamond sign if you're clubbed, excuse me, uh as, as you'll see at the top, you have broader nail bed and uh this is due to increased capillary um uh angiogenesis in your fingers and you will lose that normal diamond shape. So that's called the Sharo sign, not shamrock sign as we just had the Shamrock marathon, the Sharo sign, this is clubbing, uh, and, and, uh, generally is due to SATS that are, that are under 85% for protracted periods of time. So that is your, your hypertrophic osteoarthropathy. Um, this is AAA, not a complete list and I don't expect anyone to digest all of this at once, but AAA list of some of the multisystem effects that we get from congeal heart disease. The musculoskeletal findings are there. We talked about the clubbing and the gout already, the neuros, we've talked about the confusion, the fatigue, um and brain absence. Uh There's a, there's a patient who's been hospitalized here a few times and I think uh several of you all have taken care of him who has Eisen who we do. He is one of the only ones that we still do fully for because when his hemoglobin gets over about 21 his behavior completely changes. He's usually a docile nice kind, kind of affable guy and he becomes very mean, very ory, very uh very much like AAA sleep deprived surgeon when he is not uh when he has a hemoglobin that is not uh uh below 20 or so. So he uh I do send him uh a couple of times a year, excuse me to my wife's office where he gets therapeutic phlebotomy, replaced very quickly with Saline. So he doesn't get volume deplete because that would be bad for him. Uh And then his behavior completely changes. But that is not a AAA quick point. That is not something that we routinely do anymore that was done in the sixties, seventies and eighties. Uh, and even into the nineties, I, it is not routinely done anymore that has been looked at and the mortality is higher when we do that compared to just keeping people with the hemoglobin in the high teens. Um, but you can get varices. It's common to have gallbladder, dysfunction, liver dysfunction and uh hematologic abnormalities. Um And I, I'm not sure if doctor Iyer is on but uh but this is what's gonna get him interested. Uh arrhythmias are quite common, excuse me. Uh um from cardiac complications and endocarditis. Both of those are very um uh are are common cardiac complications, excuse me, I gotta take up drinking apparently. Um uh and diastolic dysfunction. We've talked about some of these other issues. Uh Oh, iron deficiency, I will bring that up. That's a commonly uh uh a good general internal medicine problem that we overlook. Uh many of these patients are, as I said, producing many more red blood cells. They need more red blood cell um uh components. So we need to make sure that their folate B 12 and iron stores are uh are adequate. Uh This is a major problem uh for our patients with, with pulmonary hypertension associated with congenital heart disease. Um ok. So what are some of the general management techniques Um So some of you have seen in my notes uh when I, when, when I come and, and see some of these adults with congenital heart disease who have pulmonary hypertension or Eisen Manger, I'll put some of these management principles on here. Um uh In, in the note. Uh So I think it's, it's important to, to review some of these. Now, the first is don't volume deplete them, they need their preload, They do not want to be uh dehydrated or vasodilate in doing so. Uh you're generally going to impair their pulmonary blood flow. That was certainly true for Kim. So if her blood pressure, given her anatomy, if her blood pressure were low, uh either because of vasodilation or phlebotomy or sepsis or, or, or um whatever or, or vasodilation from uh pharmacologic um induction of anesthesia. All those things can really complicate um her oxygenation leading to tissue hypoxia acidosis. And then you get into the spiral of cardiac dysfunction, you can never recover from that. And we have that unfortunately at the children's hospital uh occasionally and it's very difficult to recover from from our cytic patients or those with congenital heart disease. So please try and avoid dehydration and vasodilation. We do not let them do strenuous exercise or competitive sports. Uh isometric activities are, are really frowned upon as well, but we do want them to stay moderately mild to moderately active. Kim did not sit in a chair um except when she was working at Chesapeake uh school system. Um but she was uh a, as active as she could be high altitude as we joked about before is not a joke. That is something that we really do try and avoid air filters on ivs. I'm I, I trumpet this from, from the, the, the tree tops when I'm seeing a lot of these patients who are our single ventricle patients, particulates little air bubbles, all sorts of things um can go into peripheral ivs that will go as we've seen in this population obligate right to left and it's gonna cause a problem whether it's gonna go to an eye, a brain, a kidney, uh uh a mesenteric artery, it's gonna cause a problem. So please air filters the hemo floors have them and uh because they're used for, for chemo. Um it's the same filters as are used for a Theodor infusion. So a lot in the IC U have them. Please put the, the, the 0.6 micron air filters on all IV lines. Don't let the nurses take them off. Um We want to try and uh immunize them against uh pulmonary pathogens because pulmonary uh pathology, especially infectious disease in the lungs is catastrophic. We've talked about the iron. Uh We've talked a little bit about anesthetic management where we don't want them to become hypotensive leading to more right to left shunting and acidosis. Uh pregnancy uh is a bad disease. No offense. To Doctor Melody Adler, but pregnancy is a bad disease and should be avoided, especially in this, in this uh in this population and estrogens are bad, of course, because they like smoking will increase the risk for thrombosis. So, in most of our patients with congenital heart disease, but especially those with congenital with uh pulmonary hypertension, we avoid estrogens. Um and we don't want long term indwelling cardiac devices, pacemakers, um or uh or uh central lines, et cetera. We would prefer an epicardial location if we can given the thrombotic risk of those. Uh and then the elevated endocarditis risk um in the IC U. If you're, if you're taking care of these patients in, in an IC U setting here, we like what I call luxury oxygenation. You may not need it, but you should get it um using fio two s of 60 to 100% to try and really not long term but, but short term to try and really um provide them with the most oxygen uh uh delivery to the, to the tissue as possible. Given their limitations, we would rather they be a bit hyperventilated. We would rather them have PC O twos in the low thirties rather than in the low forties, which will lead to more pulmonary vasodilation. We also of course, don't want any acidosis whether it's metabolic. Of course, the top is respiratory. We don't want acidosis of any form, lower tidal volume ventilation uh to avoid Alvear hyperinflation uh is, is important and we'll, we'll shoot for 6 to 8 CCS uh uh per kg of ideal body weight, which is important. Um We've already mentioned the, the importance of not being anemic um and not having iron deficiency, we need more oxygen carrying capacity, temperature management. Um I I is not always a problem in our IC U uh or in the patients who are being sedated, but we don't want them to be febrile or to be cold and be vasoconstricted. And again, don't dry them out. You don't give them huge amounts of volume but but don't dry them out. So this is the, the the same sort of thing that I put in in my notes. Many of you guys have seen this um uh the only thing that's, that's different here. This is again, what I put in most of my notes is don't expect oxygen saturations above 90 in many of our patients, 75 to 85% is all we need. Um And in Kim's case, we would take things in anything beginning with the seven was great. She was often not there. So uh lastly, just in the last uh final few minutes, what are some of the treatment uh or therapeutic modalities that we use now? And I love this diagram from the New England Journal several years ago because I think it very nicely compartmentalizes uh the, the the different mechanisms uh of our current therapies and, and, and the pathways in which they either inhibit or augment. So I I'll, I'll start um uh on the on the uh endothelin pathway. Um And we use a lot of endothelin receptor antagonists and these have the best data for uh patients with heart disease. And it was actually the only therapeutic modality that Kim tolerated. We tried everything else on here as her parents know. Um But this is the only thing she tolerated. So tan also called tracker is the brand name that has the best data for congenital heart disease. But really, we believe it's likely a class effect. These you can either be an endothelin A and B or a nonselective in inhibitor antagonist. And that's what Beinin is. The more selective endothelin A receptor antagonist like Ambery or Matan also called Summit um which are the newer agents um just inhibit endothelin A. But there is no data importantly to say that either being selective or nonselective is better. So, so that's we, we we as a field are still working on, on figuring that out but inhibiting uh the, the uh the the production of, of, of endothelin leads to less vasoconstriction and less uh fibroblast proliferation and smooth muscle proliferation. So that's how endothelin receptor antagonists work. Um They, they prohibit uh vasoconstriction proliferation from the uh the endothelin um uh uh molecules in the lungs. The nitric oxide pathway, we're used to giving inhaled nitric oxide which uh which of course will increase cyclic GMP leading to more vasodilation. Um But if we use PDE five inhibitors or phospho detras five inhibitors like Psy Tadalafil or an emerging agent that's been approved in Europe and will be coming to this country called the eoi. Um All of those inhibit uh phyo Diaa type five which prohibits uh degradation of s of cyclic GMP. So if you inhibit PDE five, then you have more cyclic GMP. It's, it's kind of uh uh uh it's different than actually just boosting C GMP um exogenously. Um But both inhaled nitric oxide and these oral or IV agents um can increase cyclic GMP which has the same sort of effects as as the endothelin receptor antagonist, but a different mechanism, they lead to vaso dilation as opposed to inhibiting vasoconstriction. Uh And they have more anti proliferation of uh uh a fibroblast. And lastly, the, the pros thelin pathway, uh we're used to flow land here or Remodulin also called trap prosy. Um IOP prost is less commonly used than op prosy or trap prostin. Um And there's a new oral prostacyclin receptor antagonist called sole uh that, that is being used. And all these increased cyclic A MP again, leading to more vasodilation and anti proliferation. So, three different method mechanisms, all achieving, attempting to achieve the same goal of either vasodilation or inhibition of vasoconstriction and less smooth muscle proliferation. Fewer fibroblasts in the smooth muscle of the lung. So your nitric oxide pathway, your PD five inhibitors. And uh those are oral, of course, there is an inhaled form that's nitric oxide, your prostacyclin pathway. Um Those can be either oral, as we said, sole or flow land or trap prosy infused. There is inhaled, there are inhaled versions as well. Um uh inhaled trap prostin or Raulin and endothelin uh uh agents. Those are oral. Um I'm gonna skip through this. Um I'm gonna skip through this in the interest of time and say the pulmonary hypertension medicines. Please don't stop them abruptly. That generally does not go well, especially your prostacyclin analogs. Um So uh just know what, what agents, uh half lives are um Remodulin if you lose the IV, we have several kids in the community on Remodulin. Um We have, uh we, we've done that of course, rather than flow and because the half life is longer, they can get to the er, and get a new line started uh without having a pulmonary hypertensive crisis much better than flow land where you only have a few minutes. Um Bean is the only FDA approved uh uh pulmonary hypertension therapy for congenital heart disease, like uh Eisenmenger's uh and pediatrics. Uh But again, we believe that it's a class effect. Um but a quick review, endothelin receptor antagonists do cause birth defects. We cannot have them uh in women who are pregnant. Um So even though both we watch both liver function tests and pregnancy tests, Amberin and, um, and others in that class, we don't have to watch the liver function tests as closely. But everyone still needs, um, monthly, uh, uh, pregnancy tests. Even some of my women who have had, uh, hysterectomies, which I, for the life of me can't figure out why the FDA requires that. I fought that about two months ago and I lost with a nice letter from them. Um, So, uh you still have to uh she, she still thinks it's ridiculous too, but she does pee on a stick once a month because we have to um you, you still need to be cautious if, if you're, if you're pregnant and uh if, if a um caregiver who might become pregnant is handling these medicines for the patients, they should wear gloves because they are trato. So, uh lastly just the, the, the therapeutic pathway um for our patients with Eisen Minger, we will start with endothelin receptor antagonists like Bothy 10 or uh Ambery 10, which is what Kim was on as first line treatment. Once we start getting into the NYH A 2 to 3 classification. Although most people are starting now when we get into NYJ class two. After that, we will consider adding PDE five inhibitors like sildenafil or Tadalafil. Um We might consider a subcutaneous or inhaled Prosta like trap prosy uh and even go down the heart lung transplant list. Uh Only if our goals as you see, there uh are not met or our symptoms progress. Uh and, and coming back to Kim, we did try all of those things. Um but she didn't tolerate those for, for various reasons. Um So at, at the end of the day, um this is a, by the way, a great review article from last year on Eisen Manger Syndrome published in the journal of the American College of Cardiology. So for those of you who are interested last year, again, there's an excellent review article. Uh there are lots of things that need to occur for our patients with congenital heart disease. We want to keep them in sinus rhythm. Uh For our ep colleagues, by the way, um we want to uh not have them smoke, to have them exercise, to have them get iron supplements, to keep them well hydrated, to not uh full bottom them routinely. Um all of these things can lead to more and not have them get pregnant to, to more holistic care of these patients with congenital heart disease. Uh and that's what's gonna help them leave lead longer lives. So lastly, I just want to talk about uh patients uh with congenital heart disease in general and how we can partner uh with our adult cardiology colleagues, as I mentioned before, there is a board certification to take care of adults with congenital heart disease. I have my own thoughts that that is not a good idea. Um but I, I did sort of by peer pressure, decide to play along. There are three, board certified physicians in Hampton Roads who take care of adults with congenital heart disease. But, uh, relatively few in the commonwealth. There's, there, there are only two in Richmond, uh, that I know of. Uh, they're only, uh, there's nobody at E VA right now who's board certified to take care of adults with congenital heart disease. Although I think that they are getting one. So there are a few in northern Virginia, there are relatively few in the country. Um, Doctor Basin is here today myself and my partner, Doctor Hartke, um, who dresses up as a good, uh German man. I'm apparently a good. Um, this population is increasing. I have two more slides. This is showing our own internal data from, from CHKD. I established the program in 2007, but I really didn't start keeping data until the first entire year I was here, which was 2008. And you can see, I only saw 58 adult congenital patients, um, uh or 60 rather in that year. Last year, we saw 577 adults with congenital heart disease. These are not, these are individual patients, these are not just how many times we see them in the office. Um This is equating now to about 50 patient visits a month and it's primarily me. I'm seeing about 85 to 88% of these. Uh Doctor Hartke also does pulmonary hypertension in the, in the teen and, and child. So she sees a lot of those patients. So I'm seeing most of these patients. I can't speak for Doctor Basin, how many he's seeing in his office. But this is a a uh I'm gonna run into a limit. I'm not gonna be able to do all this myself. I'm already not able to do it. I need and want to partner with my, with my adult cardiology colleagues, not just on the procedural level but uh on the uh on the office side, we are having increasing numbers of these and I want to point out the number of Norfolk General or heart hospital visits. I saw two in my first year. I saw 81 patients last year inpatient. It's not sustainable for our program here locally. It's not sustainable for me. I need to partner with you guys. I want to do that to be able to uh to continue to provide high quality care to our patients with congenital heart disease in Hampton Roads right now. It's a as you can see, uh I've put our pediatric uh data on here as well. We see about 1000 patients um uh about 1000 patients a month in pediatric cardiology amongst the nine of us there at CHKD. That percentage of, of what percent uh represent adults again. Uh uh 22 years old and older is how we define that. Um That is now just over 5% of our patient population as you can see in the graph down below. Um and it started uh or just a few years ago, it was only 3.4%. This is dramatically increasing. We can see this coming and we really want your help. My patients are cute when I see pediatric cardiology patients way cuter than than the folks in this building. No offense. Um Some of you guys know some of these patients these have recently been hospitalized here at Centra. They have grown up. Um uh and doctor do your patients say I love my cardiologist. So they wear little one saying that they do, ok, you have a different patient population than others. Um uh Doctor Eer doesn't have patients that say I love my cardiologist. Uh but they do grow up to become adults with congenital heart disease and doctor will be ablating this patient on the left. He knows him well. Um but this is just from the last uh week where where? And that patient on the right by the way is a single ventricle. His SATS are about 88% but he is 6 ft two. So it did not impair his somatic growth. Um He's, he, he's a big guy and his aorta is pretty big and he's gonna need something done to that 11 day. Uh but until then he's, he's doing well, uh they do become adults living with congenital heart disease. Um And I hope that this is not uh in their future. This is a, a picture that I took. You can see from Lynn Haven Parkway just a week ago. This is uh a, a patient uh I hope of of, of doctor Jets or Doctor Adler or somebody else. Um Hopefully not of Doctor Eggert where they're smoking with their oxygen. This is not what we expect for our patients with congenital heart disease. Um So once again, I'll pay tribute to Kim and thank her parents and her husband Mike for uh for being here and for uh for providing some of the funds to establish this first annual Kim starring memorial lecture in congenital heart disease. Thank you. Published June 15, 2023 Created by Related Presenters Alexander Ellis, MD Cardiology Children's Hospital of The King's Daughters
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