UCSF pediatric cardiologist Kishor Avasarala, MD, discusses how pediatricians can ensure appropriate cardiac care for children infected with COVID-19. He clarifies keys to understanding MIS-C (such as illness phases and age group factors), as well as testing parameters and follow-up essentials. Bonus: how to safeguard a return to sports for kids who’ve had COVID.
three. The objectives world type is this. Try and and describe things as a case study for primary politicians so they can actually really relate to clinical situations in this setting. Um, try and define why this is a problem. What can primary Pediatrician's due to manage this? Hopefully the very mild ones in their office, the sequence presenting mawr to the hospital and the er setting. Um, what does a primary pediatrician need to refer to a specialist or when Rather, and can any of these be managed in the office while they're reading for a specialist to see these kids on duh telehealth availability from UCSF. So we'll we'll talk about those things. So eso briefly, we all have been inundated with code information, so I'm not going to spend a lot of time on the the viral ideology or anything else. The focus will be very narrow. Just stick to pediatric age group cardiovascular manifestations. What we know about it, how that is evolving. What are the complications, how to manage those, and so just that small focus. So we're clearly seeing a larger number of kids who are testing positive for this virus. Thankfully, majority of them are asymptomatic and or minimally symptomatic, which is what we're happy about. But there is a small subset where these kids air significantly ill, and the studies are very variable on what that percentage is for the really sick kids, anywhere from 4 to 10% in various different Chinese studies in Italian studies, but quite variable in this number. And this will evolve as we get larger case Siri's, so we'll be able to further define that percentage better. So what we're seeing is essentially two phases off this illness, with reference to the cardiovascular component off of it. So the early phase this is kind of coincident with wherever there's regional peaks off the covert infection on we call it a cute covet 19 in the late presentation is about 2 to 6 weeks Post Peak. And that is the so called M I S E multi system inflammatory syndrome in Children, which we have heard about it and we will discuss briefly at this point. All right, so in general, Children represent about 9% off the Total Cove in cases that representing and as we again now, they don't become as sick as often as the adults do. Our hospitalization rates are much lower than adults at any one point in this hospital. Um, the Oakland campus, especially. We're seeing maybe 3 to 4 kids who are in patients with the illness on duh. Typically, maybe one off them or to off them are in the I. C. U. Um, the number of kids who have been on the ventilators are also in literally single digits. Um, I think we have had only one kid on ECMO to my knowledge base, Onda Geun, these air changing all the time. So I'm just quoting these numbers because I want you to understand that. Fortunately, these numbers are small. They still are important, but they're small. We see definitely a preponderance off infection in Hispanic Children and non Hispanic African American ethnicity. Children Onda. Clearly, the outcome seemed to be worse in that age group. The morbidity and mortality are also worse in that ethnicity that that I described all right. For some reason, the Children, who are younger than two years of age seemed to have the higher risk and the more severe form of illness when compared to the older Children and newborns. Roughly about 2 to 5% of newborns. If they're born to Cove, it positive moms may test positive. Don't necessarily not manifesting any significant illness. So a majority of our Children usually milder, cold like presentations, and most of them are recovering in about 7 to 10 days, as you all know. So if you look at the acute presentation, it is anti aging, mediated and again common knowledge here that it's the binding off spike protein. Those red spikes on the coronavirus picture with the two receptors on the cell surface that allows the virus to enter into the end of the little cells and begin the onset off infection with Verena. This is similar to the adults and the one that causes more respiratory symptoms. So the pre existing conditions that we're seeing in Children also seemed to make a little bit the adult age group, which is obesity. Clearly, significant risk factor hypertension, diabetes and chronic lung disease is overlap with adults, and I didn't add one here, and that is congenital heart disease, even post repair. We're seeing a slightly higher chance, and kids who have had congenital heart disease repair, uh, not well documented, in percentage but we see that as a za risk factor. So the cardiac involvement generally manifests due to my oh cardio injury. And you can see that as a reflection by seeing that the cardiac enzyme definitely increased in many off these sick kids, and I'll go over those details on. We see a decreased left ventricular function due to myocardial injury directly by inflammation related, uh, injury to the my accordion and the way they present when they have cardiac involvement is most of the time. Azan acute viral myocarditis picture very similar to the type that is seen with other types off viral myocarditis pictures. In general, management is very similar to the adult management. Um, if we have significant ventilatory issues, then in that small setting they need a ventilator support. Otherwise, it's mostly oxygen support and non invasive ventilatory support, and we have learned from experience to use the ventilatory support Onley when it's absolutely needed on. That seems to have helped in decreasing mortality issues and mobility issues. Majority of these kids present with significant refractory hypertension, so they end up on China Tropic support with either nana preference or if nothing along with fluid challenge support that we provide them. And as you will learn and you already know, a lot of these manifestations are related to the cytokine surge on DSO. The anti inflammatory medications are definitely helping. This includes high those aspirin, intravenous immunoglobulin infusions. You know, one or two doses as needed. Intravenous steroids definitely have changed the outcome substantially. As we learned over time, Um, antiviral medications like remedies over which delay our stop viral replication. And lastly, Mina modulators, which are ill six inhibitor infusions and top plays A mob and Anakin ra are examples off those. So these air, all well known to all of us who are learning management off covert infections Now, the cardiac involvement again I'm emphasizing is primarily myocardial injury on we we talked about those two, which is decreased decreased function, uh, worsening levels of cardiac enzymes, primarily troponin and, um, brain nitro heretic peptide levels BNP. And we'll discuss the acute myocarditis pictures. So the late presentations is the essentially the my SC. So this is typically 2 to 6 weeks Post peak. It is antibody mediated. So many of these kids may have a prior history off viral like illness or a positive vantage and test, but at this time there were many times negative on the standard. Auntie Jen mediated covert testing. Um, and they have less respiratory component or involvement, and it's It's more G I skin manifestations in younger Children, neurologic symptoms and all the Children and cardiac involvement in all ages off the pediatric spectrum. So 80% off Children present with some form of cardiac involvement in the setting off my SC Eso cardiology is definitely a big part of evaluation of this kids. These kids starting from when they show up in the er sick toe till they get into the I. C. U and subsequent management, they are significantly take a cardiac at baseline. Typically, heart rates off over 1 30 and very hypertensive, requiring very aggressive fluid resuscitation and china tropic resuscitation. And so they're typically on one or two pressers. By the time they get into the I C. U. Um, they a significant percent eight of them have left ventricular systolic dysfunction. On this, we measure two indices, which is ejection fraction and shortening fraction. Both are towards the same measure, just different ways of measurement, and their numbers are usually less than 55%. Um, is the abnormality there? And it could be severe. Some of the very severe kids can be as low as ejection fractions of 20% or 30%. And then the intermediate ones are in the 30 and 40% range, depending upon the severity off myocardial dysfunction. Right? Like in the Kawasaki situation. We're seeing coronary artery involvement in about 88% off this cohort, usually involving the left anterior descending or the right coronary, which is primarily dilation off, these eventually leading onto aneurysms. And we have these core numbers for these that we look at with echoes to measure what we call us. Coronary violations associated with pericarditis or pericardial effusions. And clinically, you could hear a rub when you see cardiac dysfunction clinically, that correlates with tachycardia and a gallop rhythm. So it's useful as you listen. If you're hearing a Gallup in attack, a Kartik patient with this story, quite likely we're dealing with associative myocarditis and ventricular dysfunction, cardiac enzymes air clearly elevated in a big number off these patients, and that would be troponin t troponin I and B and peace, um, cardiac arrhythmias. A more of an issue in the adult population in the pediatric population. Going through different case Siri's It's mostly more super ventricular arrhythmias and atrial arrhythmias. Few reported cases with PVCs very, very few with, uh, complicated forms off ventricular district means like V, T and B F. And of course, in the very severe cases, we have the requirement for pulmonary or cardiopulmonary resuscitation. Again, just a few numbers. These numbers air changing the case. Siri's air small. So this is the current numbers, but you know, we'll see where they are down line. The key is take a cardia 97%. So pretty much more than what just fever is so inappropriate. Tachycardia at base line at rest. It's a very sensitive kind of bedside finding for people to suspect there is something more than just fever causing tech cardia. So I would keep reemphasizing inappropriate tachycardia as an important clinical finding to suspect myocarditis. Sometimes it's hard to pick up my car like this and this patients, and if you miss it and they go home or obviously into quarantine, if they are positive, um, it can have worse outcomes, so we don't want to miss it. So our suspicion, Um, index of suspicion should be very high to start. Keep keep to keep looking for myocarditis in this setting 78% or take it nick over 30% or hypertensive and a good percentage of them. Roughly 40 to 50 have either Kawasaki like or atypical Kawasaki like features. And I will kind of describe those in my future slides on DFO 40% off. These are showing coronary artery involvement primarily in the form off coronary artery dilation and a certain percentage of them actually having coronary aneurysms on again. Ah, huge percentage. 90% of them having elevated BNP levels substantially elevation off these numbers, not subtle and about 73% of them with proponents. So normally, when kids come in, we beg and plead with, er, doctors and pediatrics not to send proponents and these kind of enzymes to confuse the issue. But if we are seeing these symptoms, we actually request them to send these enzymes to give us an idea if there is myocardial enzyme leak which will make us suspicious off possible myocarditis underlying the presentation. So again, this is the common, um, cardiac involvement in this setting off m i c and that's my car. Light is in Kawasaki, like Kawasaki like picture. Um, To be very honest, we haven't seen too many off my SC riel complete M. I s see kids in this institution. We are very, very highly suspicious because of the story. And we're waiting to see more changes if they happen. But we have seen a few who have met a few of the criteria and and we've been aggressively monitoring them, but not many so far in our setting. My card itis is the hallmark off myocardial inflammation injury. And it's the old criteria that we're still using the Dallas criteria to to describe the actual inflammatory change in the myocardial, which is necrosis and degeneration off adjacent mine sites. So again, they can present with tachycardia chest pain, lethargy, E K G changes which show essentially tachycardia and diffuse S t segment abnormalities which are pretty dramatic when you see them elevated troponin and BNP levels. And as expected, we will get an e k g and an echo on all these. When we have a suspicion and by echo, we're looking and seeing left ventricular dysfunction or LV dilation and mitral regurgitation, which is secondary to the left ventricular dysfunction and dilation. Um, if we have any questions, we get a cardiac m r I, but we never do a biopsy. It used to be something that was done in the past, because the memories are quite sensitive to show us delayed enhancement and also give us an idea about myocardial function. The degree off mitral valve insufficiency on other questions. Many off the typical myocarditis we see in Children are virally mediated, and it's usually with the intra virus. Coxsackie. I don't know parvo and CBB. We're looking at M I S C. And it seems like it's a very similar type of presentation because of the cove, it 19 viral infection and the treatment. It depends on how severe the cardiac disease is. And again we talked about I v i g. Hi does aspirin. I know tropes and I v steroids and, of course, immunoglobulin. It's like at, um, I'll six inhibitors and and as a corollary in the general pediatric population, myocarditis is very rare. Um, though viral infections are common. That's a very small percentage of kids who actually developed frank myocarditis following viral infections so Mike arthritis and covet 19. Obviously, this is more prevalent in than in the normal population. So if you look at the New York data there, more of our mixes have been reported. Um, they diagnosed my card itis in 52% off these m I s see patients. The elevated cardiac enzymes were seen in 90% off the kids who were picked up in the New York cohort, uh, in whom either they were confirmed or suspected. M i s E situation. One of the larger studies here is 186 patients. This work from 26 states. Obviously, because the incidents is so low, this is all multi center studies to give us a little bigger sample. So the data is more meaningful. And again, in this setting, roughly about 80% have cardiac involvement. Um, and again, majority of these are having enzyme leaks. BNP 73% troponin, 50% in this study. And about roughly about 40% had systolic dysfunction off the left ventricle by echo criteria. If you look at the stable, you can see um, try and see if I can move that. You'll see that um, in these three categories, the skin manifestations there, you know, fairly common. Then come the G I. Manifestations in different age groups seem to be a little bit more almost the same in all three age groups. The interesting thing is, the Kawasaki or a typical picture seemed to be more common in the younger kids and less common in the older kids. And the opposite is with myocarditis. It's a little less common, like about 40% in the younger ones and almost 73% in the 13 to 20 year kids. So this is kind of opposite presentations here and then the neurologic involvement there. So I'm just trying to highlight that the myocarditis seems to be in the teenage population. More all of you has pediatricians know the classic on, um, a typical features of cava stocking. I'll just reiterate just a little bit. We were greater than five days on before, out of five off These following in Canada, um, criteria macula, popularly rash, typically on the trunk. As you can see here. Conjunctivitis, bilateral and limbic sparing. You can see it. Nice picture here because of changes. Red cracked lips, strawberry tongue and palm and sole swelling, as you can see here. And Lynn Fenton apathy. So these are. These are fairly typical that all of us look all the time in February. Kids Atypical presentation is fever greater than five days and 2 to 3 or five off the classic symptoms. So here is fever. More than seven days in India. White count, high platelets, high low albumin elevated LTs on sterile Peoria. Now the echo kind of helps in some situations where we have in a typical picture or borderline pictures because you can see from Yellen study that when they looked at all patients who actually had corner aneurysms backwards and looked and they actually saw that a third off them did not really meet the classic Kawasaki criteria off 4 to 5 and had somewhat atypical presentation. So when in doubt, our I D colleagues definitely ask us to look at an echocardiogram to help if there is corner involvement or not, this is kind of ah, funny term that we coined ourselves here, where if you have a kid who has a college lucky disease or Kawasaki like picture and has a shock, um, we call it cover Shockey because it has a very distinctive presentation. We see it in about 5% of Kawasaki kids, so it's definitely, thankfully, a small percentage. It mimics the clinical presentation of toxic shock syndrome. They could have G I symptoms. The difference is that they have thrown both sides opinion here rather than from both psychosis. They have liver involvement with LFTs koa give ah parties the dime er elevations CRP elevations and again over 80% with elevated cardiac enzymes. And we have way, uh, noticed cardiac dysfunction with decreased the F and, uh, mitral regards on echo increased risk for corner aneurysms in this setting. And the other interesting thing is one in this picture, there seem to be more. I've i d resistant and end up either requiring extra doses of I V i g or get immunoglobulin infusions. So same thing to reiterate a cardiac involvement in M. I s C is either my card itis or Kawasaki like picture and Kawasaki shock a za combination, and this together is what you tend to see in this setting off my SC. Okay, um, then I'm going to talk about primarily what you pediatricians have to think about when you're clearing these kids to go back to sports activity, which is gonna happen in the next few weeks or months. A. So how comfortable we are in sending these kids back to sports. Especially athletic, not recreational, but very athletic sports. Um, at the varsity level. For people either who have been sick with covered infection and recovered or who were just Corbett positive didn't have the clinical illness. What do we take into consideration and how do we feel comfortable clearing them? So returning to sports participation after a covert infection will be this significant question that you guys will be getting from families and school authorities. And the approach is going to differ in pediatrics when compared to adults. So what I mean by that ISS majority of our kids, as you know, have a very mild illness. And in those situations, once they have recovered fully clinically and have completed their quarantine and they have no evidence of myocardial injury, that means no Myo card itis like a picture or, you know, those those kind of issues may come easily clear them for participation without extensive cardiac testing. So thankfully, majority of our kids will belong to this group. Now this is a very useful table that I like to highlight. So here it's this is pediatric patients with a history of covert 19 infection and who are asymptomatic for more than 14 days. Those are the ones that were clear. If they're asymptomatic or mild symptoms, no fever and less than three days of symptoms, you hear them for participation right away. On the other hand, if they have moderate symptoms meaning prolonged fevers, bed rest Um, no hospitalization and no abnormal cardiac testing and they're less than 12 years we picked this age because this sports participation is less intense in this age group, and so we can then clear them for participation. But the same cohort. If they're greater than 12, then they're more likely to have high intensity, competitive activities. And so what we request is this particular group should probably think we should think in terms of getting an e. C G prior to participation. They have normally cg clear for participation. We haven't abnormally CG then Goto, a pediatric cardiologist for clearance, Uh, in addition to probably get a Neco along with the BCG because of the concern from myocarditis because it can be a subclinical myocarditis sometimes that you don't want to miss. Obviously, this is the more severe symptoms here. So here, very lightly they have myocarditis. So we're gonna treat them like any other viral myocarditis, which is complete rest and exercise restriction for 3 to 6 months after being after they have recovered from the illness. They get testing with E C. G s. They get an echo, they get a Holter to look for arrhythmias. You would even think in terms of a cardiac emery and a stress test as part of the work up in this small subgroup of patients. So this is a very useful table on deciding how we can clear them to come back. Okay. Should we test all these Children before they go on? Attend sports on DPI recommendation is that we don't need to test them unless the athlete is symptomatic or the athlete has bean exposed to someone who is known to be recently infected with the covert choir interest. Clearly, there is no recommendation to do antibody testing at this time. In this population of kids who want to go back for athletic sports and We always are asking parents to report if the athletes or any household contacts, exhibit any signs or symptoms off the infection or the test positive for the virus, even if they're asymptomatic, Um, and the individual should be held out off all practicing games until they finish up. The 100 recommended isolation or quarantine periods are expired because we don't want other kids to get sick or the coaches to be exposed to them now those with severe presentations. If they're hypertensive, they have atrial arrhythmias, less likely ventricular arrhythmias, ventilatory support ECMO. Obviously, they're going to get very slow recovery and in those cases will restrict them from exercise for 3 to 6 months, as I already discussed. Okay, we're clearly seeing a much higher Kawasaki like illness, Um, in this setting experience that more in Italy on due to some degree in the East Coast, the possible mechanisms for the cardiac dysfunction are primarily myocardial, stunning or oedema related to the a severe inflammatory state and direct myocardial injury by the virus and violin Mia and to some degree high, poxy me a secondary to the viral pneumonia. And that's there's It's probably all of them together So the issue is primarily the severe systemic immune response with this massive cytokine release causing direct tissue damage or both. And the the damage to the cardiac tissue is the main contributor to the my card itis and the resulting heart failure. So they're a couple of things here again that I was able to summarize from my literature search kids with past history of Pyongyang, heart disease, bpd, respiratory, respiratory tract abnormalities, human clump in apathy is like sickle cell disease, severe malnutrition and underlying immune deficiency disorders. Thes are the groups where it seems to be a more severe clinical manifest station off the disease, including cardiovascular. This is from the Chinese experience that we're seeing, and it's interesting we don't understand this very well. But pulmonary hypertension seems to be much, much lower in our Children with cardiac, um, involvement with covet on dso Also right heart failure. We're mostly seeing left ventricular dysfunction systolic and to some degree diastolic dysfunction. Um, the mechanism for Kobe 19 related injury and shock is still not clear. And, uh, sorry about this thing. So it z primarily cytokine mediated, uh, my car deal inflammation as we already talked about, and I did mention that it's more a trailer with means that we're seeing than ventricular arrhythmias. All right, a couple of things about how to follow these kids long term. And the reasoning behind long term follow up is because we don't know the what type of injury is happening to the cardiac Meyer sites. Once the Maya Carl Itis Covic related this happening. Are there any long term issues with diastolic dysfunction, systolic dysfunction? So not having answers to that? The only way to get those answers is to once they have the illness to follow them carefully. Long term, even if there's systolic function improves, we're not sure about their diastolic dysfunction, and we need to We need to follow that. So we like to have longitudinal registries for that. Um, the other concern is we're using many drugs. Thio treat these patients, Um, one of them obviously is hydrochloric, in which, thankfully, we're not using antiviral drugs, which can also be cardio toxic in some cases, and this is a inflamed myocardial with ventricular dysfunction. So what are the effects off these drugs on on the inflamed my accordion? And will they increase the cardio toxicity because of that, it's also a good question. We don't have the answers for that, and we have to keep getting those. So this little thing that I wrote there is, If you don't look for it, you may not find it. And I'm alluding to my card itis, especially the subclinical version, so we should have a high suspicion for it. We should watch for inappropriate tachycardia in these Children. And when we have suspicion, we have to get the cardiac enzymes and look at E k g changes in addition to other clinical findings. Okay, And lastly, what do we do? And to learn more about this disease processes, we have to agree on all the definitions. Collect data. Onda obviously research, research, research. So fund and get more registries. Um, better child screening larger population studies with multi center studies on the inequity is primarily what I mentioned about why the Hispanic and African American kids air getting affected and how we can decrease that inequity with policy changes on. I think that was important. And obviously this slide is our slide for, um telling you how to be able to get a hold of us for any questions you have will be glad to get back to you for those questions
