COVID-19 infections and vaccines, as well as certain cancer treatments, can play roles in myocarditis – whose incidence has increased about tenfold in recent years. This update from cardiologist Clifton Watt, MD, clarifies that selecting appropriate diagnostic and therapeutic tools depends on many factors, from the case’s severity to the patient's health status and history. Illustrating his talk with tissue biopsy and cardiac MRI images, he discusses the range of inflammation called myocarditis, how and when to use imaging, options for critically ill patients, and how to counsel young athletes with post-vaccine chest pain. Bonus: Hear about novel treatments to consider in the ICU setting.
Myocarditis. Um, now we're in 2024 and we've uh been through, um, a lot fairly recently, uh with regards to myocarditis, um, and some of it's invaded sort of the, the, the, the nonm medical news space too. So, so, um, uh, you know, lots of us have heard about um uh about myocarditis, myocarditis even more recently. Um So I'll, I'll talk uh hopefully about some of these kind of new, new and, and uh, and fresh uh things that we know about and uh milk car it is and have heard about. All right. All right. So, so, so a brief outline again, I'll talk a little bit about, um, updates on our understanding of what myocarditis is and what I was referring to was, of course COVID and, and how COVID and the COVID-19 vaccines uh have changed, um our understanding, um and um how we see myocarditis as a disease and how it's really affected uh the prevalence and incidence of, of this disease. Um Something also that um has been, um, more recent is certain cancer treatments and its impact on myocarditis, which I'll, which I'll bring up and, and finally, um, you know, novel treatments for myocarditis. Um, I'll, I'll spend a, spend a little bit of time on. All right. So, just, just to set the table, um, in terms of definitions and diagnosis. Um, so as we probably know, myocarditis is an inflammatory disease of the heart muscle or the myocardium. Um, and that's a very broad, as you might expect, that's a very broad, um, definition. And it's probably because, uh, it's a very broad uh uh uh broad spectrum of disorders. Um And we'll get into that. Um And you know, there's probably some, some immuno uh um immunologic basis to it, infectious nature to it. Um And you know, it's very much a very broad spectrum of, of disease state. Um And that's part of why, you know, it can be challenging to make a diagnosis of myocarditis. Um The the cur current state, the diagnosis typically is made um with multiple different methods. There's no one test that we can use to diagnose myocarditis. We certainly use the the clinical situation. Um We use histologic or um immunologic histologic sort of tissue um um diagnosed diagnostic methods um and imaging too. So, you know, imaging the heart from outside the body is, is, is now um a very commonly used. So, you know, even though the gold standard of diagnosing myocarditis is using histologic, you know, looking at the tissue under a microscope and using staining with immunologic methods. These are still considered the gold standard Um Now we're doing bio, you know, quite frequently using biomarkers like blood testing troponins, um and imaging, using echocardiography and MRI of the heart. Um So, you know, going way back, historically, you know, uh there was uh a set of criteria called the Dallas criteria that was uh going back to the eighties um proposed by uh cardiac, uh A AAA group of cardiac pathologists and this group of uh of uh providers um really looked at um classifying myocarditis um based on, you know, one biopsy. Um so tissue as well as, you know, subsequent biopsies. So not just one biopsy but, you know, multiple. Um and so that can, that could help, they proposed that that could help categories categorize myocarditis as not just, you know, a single disease process in at one time uh time point, but also sort of moving forward. Um you know, myocarditis is not just, you know, a, a process that is acute but can be, you know, acute and healed or acute and healing um or persistent or chronic. Um And so this group um proposed, uh you know, a classification system that I won't go into too much detail, but included one table in their um landmark paper here on the, on the lower right. Um Basically based on tissue biopsy. Um So again, you know, using multiple biopsies, um not just one. but the first biopsy could tell us whether there's definite myocarditis borderline or not at all. Um and then, you know, using subsequent biopsies to tell us if, you know, the myocarditis was an ongoing process. Um And what we, what we see, what we could see with biopsies um are, are multiple different possibilities. What obviously we could see is, you know, cardiac myocyte damage. So you could see, you know, you know, uh necrotic uh cells, um you could see instead of the, the, the cardiac myocyte replacement of those cardiac myocyte with um you know, vacuoles, empty sort of um hollow cells if you will um in place of the myocyte, um you know, inflammation is a, as you'll see is a huge part of, of uh what we think is myocarditis. So, inflammation could include in lymphocytes, polymorph, uh polymorphonuclear leukocytes. Um Typically T cells is, is what we see in the inflammatory um mi uh on biopsy. Um you can see fibrosis. So, scar tissue um um on biopsy. Um in certain types of myocarditis, you can see granulomas. Um um for example, in cardiac sarcoid um and the giant cell myocarditis is one of the, the more uh you know, sort of the more dangerous uh um you know, uh life threating um uh forms of myocarditis. Um um and then you can see an eosinophilic or neutrophilic. Um Yeah, um predominance um on biopsy. So, um I will uh one more slide on sort of, you know, biopsies um because this is the gold standard. Um still um uh for diagnosing myocarditis. Um, even though endomyocardial biopsy is the gold standard, uh, actually recommendations or in, in real life, uh, biopsies to assess for myocarditis are actually not, um, as commonly done as, as we might think. Um, um, and there are multiple reasons for that, but, you know, one of the main reasons is, you know, if you're, you know, putting a catheter inside the heart to take a tissue sample, you know, there can be complications. Um And obviously these complications can be very, you know, um they, they can be fatal. I mean, the, you know, the there there can be significant risk to the to the procedure. Um, so, you know, it, it, it, you know, major complication rates could be around one or 2% and include perforation of the, of the ventricle, either the left ventricle or the right ventricle. Um particularly with the right ventricle as the right ventricle wall tends to be a little thinner. Um, minor complications can, you know, I've seen go up to, you know, an incidence of 5%. So it's not a, not a completely benign procedure. So that may be one reason why biopsies for myocarditis are not, uh not always done. Um In addition, myocarditis, uh from a on a tissue level can be focal meaning, you know, it, it's, it's, it's when you biopsy a tissue, um the myocardial tissue in, in a patient with myocarditis, um you know, that that tissue uh involvement doesn't have to spread throughout the entire heart muscle. It can, it can be patchy. Um And so biopsies, um you might expect can miss the diagnosis uh for that reason. Um And, and, you know, based on s and, and probably because of some of these elements, uh biopsies are oftentimes used uh or done um mainly in higher risk patients, uh more ill patients, patients who are hospitalized um in the IC U or CCU um you know, where, you know, you may have indication to, you know, do invasive procedures anyways uh for standard of care. Um So that's where biopsies are more often done. Um Whereas in lower risk patients, um and we'll get into this, uh you know, biopsies are less often done and we're often more often resorting to, you know, doing blood work and looking at the clinical situation and doing EKG S and doing noninvasive testing like echocardiography and, and uh cardiac MRI. Um So, so that's sort of an, an, an sort of an initial um um sort of primer on, on how we approach uh diagnosis. Um Yeah, and so, so, you know, as you can see sort of in this lower right corner, you know, there are, there are situations where biopsy, um proven myocarditis is quite clear, you know, you can see, you know, in this, you know, the bottom panel. Um um you know, you can see a lot of inflammatory infiltrate here, you know, in, in, in the midst of the the cardiac myocyte uh tissue versus a normal sample on the top. Um And this is, this is an another uh sample from a paper um in a, in a 29 representing a 29 year old um female patient with acute myocarditis. And so, um on the left, this is a, this is a path sample pathology sample um showing if you can see, you know, these patches of, of sort of purplish stained um cells here amidst the normal myocardium. So the normal myocardium appears pink here and, and uh this is an H and E stain for the pathologist out there. Um um uh showing you know, these patches of, of, of dense aggregates of mononuclear uh leukocytes um um suggesting the diagnosis of myocarditis. Um And then on the right, this is an M ria sample, MRI of this patient um showing um what we call late gadolinium enhancement um which essentially tells us about um scar or fibrosis in a very typical pattern um consistent with myocarditis. Um and the red arrows uh shown by the red arrows here and the and the anterior se um and the mid wall, the, the mid wall of the anterior se here as well as the infra lateral wall of the left ventricle. Um what we call subendocardial left uh late Galin enhancement. So, these, these are patterns that are quite classic for myocarditis on, on cardiac MRI. All right. So, so enough about uh you know, the, the, some of the path uh pathology and imaging, although we'll get back to it. So, epidemiology. Um so I think, you know, some of us remember prior to the pandemic, um you know, feels like ages ago. But, but uh before then we, you know, their myocarditis was a well known entity. It was not a very common disorder. Um um It, you know, maybe 1 to uh 1 to 10 cases per 100,000 people per year. Um And uh incidentally, the, the, the most common uh presentation was in younger, younger males between 20 to 40 years of age and this was prior to the pandemic. Um And then, you know, as we may remember during the pandemic, uh you know, we started to, you know, see cases of myocarditis, both acute and chronic in the hospital and um outside of the hospital. Um And uh so, you know, you know, there's been a good amount of research looking at, you know, the, the numbers um and how, you know, how the incidence of myocarditis did go up um during the pandemic. So, you know, quite uh multiple fold here, you know, 2.422 to 4 or 2 to 5 patients uh cases per 1000 people um in uh with, with COVID. Um And so we, you know, this made sense to us, uh you know, COVID being a viral illness. You know, we knew that uh you know, there are in the past, we knew that there were other viruses, um you know, coronaviruses, rhinoviruses, um adenoviruses that, that could precipitate COVID uh sorry, precipitate myocarditis. And so, you know, it, it, it, it made sense to us um that COVID-19 uh SARS COVID two could do something similar. Um And uh and then, you know, when, when the COVID-19 vaccines came along, um you know, I, and I remember this uh uh very clearly uh not too long ago, but uh you know, we, we started to see cases of, of myocarditis that we thought were associated with the vaccination. Um and particularly with the MRN A vaccines um um uh pfizer um and Moderna. Um And so, you know, again, we saw these cases, you know, not too commonly. Um That, and that's important to note one case in 100,000 people vaccinated. Um We still saw the same pattern mo more commonly um you know, in younger males. Um So, um I overall, you know, there's been documentation that, you know, at least um the, the, the, the, the incidence of myocarditis and pericarditis um has gone up at least 10 times. Um you know, compared with pre COVID pre panem levels. So it's definitely something that we see and um and deal with. Um I think um luckily uh oh most of the cases um of either COVID uh 19 myocarditis and certainly COVID-19 vaccine related um myocarditis tend to be mild and um and resolve um with supportive treatment. Although, you know, at, at the hospital, I have seen, you know, patients with COVID um uh myocarditis that were very sick and, and did require a transplant. Um So, um the the spectrum of disease does um it, it is quite wide, right? Um So, um and I know, I know many of us know how these patients often present. Um they, they often present with chest pain um clinically. So, and it's oftentimes acute, um you know, along with that people can also present with shortness of breath. Um you know, dizziness, you know, multiple, no more nonspecifi symptoms. Um And that's oftentimes what we see in clinic um in the outpatient setting is, you know, people come in with chest pain, uh you know, after getting a, after contracting COVID um or after getting a vaccine, um you know, obviously this is a, this has been a maybe a more difficult situation for us in, in cardiology where, you know, we, you know, I remember during, you know, right after the COVID-19 vaccines uh came out, you know, I had a flood of patients coming in with uh chest pain and, and they, they thought that this was all vaccine related. Um And uh again, to emphasize that the, the data have shown that truly the incidence of myocarditis like more definite probable myocarditis related to the vaccine is very low. Um But, you know, the media perhaps played a role in, in, in, in this, in, in, in the sense of, well, you know, it was kind of presented in the, the, the delay, non medical media and patients, you know, when they had symptoms after a vaccine, they were worried that, you know, oh, do I have myocarditis or pericarditis related to the vaccine? You know, these were, you know, not these were new vaccines to the population. So uh there, there understandably was a lot of um worry. Um um but, but again, to, to re emphasize that, you know, the, that not only the, the numbers were o of vaccine related, um myocarditis are still quite low and the prognosis was quite good or is quite good. Um But in some cases, you know, patients can present with very severe illness. Um as I mentioned before, they can have, they can be in shock, they can be critically ill. Um you know, with heart failure and uh and uh you know, they can require mechanical support, um heart transplant. Um So, uh you know, this, this, when I read this figure, it was quite staggering to me, you know, these um you know, registry data showing, you know, almost a 30% rate of either death or transplantation um in at, at 60 days in patients with um myocarditis and cardiogenic shock um versus 2% without cardiogenic shock. Um patients with myocarditis can present with ventricular arrhythmias as well as atrial arrhythmias. Um atrial fibrillation, atrial flutter, um but ventricular tachycardia um is, is um is a more dangerous rhythm that that can be associated with myocarditis. Um A V block, um you know, sometimes require pacemaker um and sudden cardiac death. Um you know, potentially due to a ve ventricular arrhythmia. Um you know, to remind us, you know, some, you know, sometimes these patients with myocarditis um um in, in the non severe case, um they, they can have a normal EKG and a normal troponin. So these, these, these are not um tests that we can hang our hat on in terms of diagnosing myocarditis. So other things that we can use to um help diagnose uh myocarditis is imaging. Um So the kind of the, the idea behind cardiac noninvasive cardiac imaging is to look for um you know, ventricular wall motion abnormalities or left or right ventricular dysfunction um while of course, excluding uh coronary disease. So if oo of course, if we're, we, if we have patients coming in with chest pain and then they have an abnormal EKG and an abnormal troponin, then our first thought is thinking, well, are they having an acute M I, are they having a heart attack, uh myocardial infarction? And we, we, we probably have to look at their coronary arteries. Um um But if we've excluded coronary artery disease as the the etiology of their s their situation then, then myocarditis is certainly on the differential. Um and uh echo echocardiograph, echocardiography is the, you know, the first line test that we, that we use. Um It's a test that, you know, I mean, can give us an idea of, of, of uh uh of ventricular dysfunction, wall motion abnormalities. It's, it's, you know, easy to do quick um noninvasive and uh can happen very quickly in the outpatient and inpatient setting. Um Cardiac MRI is uh a, a modality that's been around for a long time. But, you know, I think in general, the its use is increasing and myocarditis is one of the, the key uh use cases for cardiac MRI. Um So we've already talked a little bit about how we can see um you know, a abnormalities like late gadolinium enhancement um um which, which I won't get too much into. This is not a radiology talk but, but uh you know, that's a finding on cardiac MRI with gadolinium contrast that is um that is consistent with scar or fibrosis. Uh but certain patterns of, of um late gadolinium enhancement, um edema, myocardial edema, we can actually measure um edema from um certain cardiac uh MRI um techniques and, and this can help us help us with the diagnosis of cardi uh myocarditis. Um keep in mind that uh that uh the diagnostic sensitivity for, for myocarditis using cardiac MRI is, is highest um um within, you know, 2 to 4 weeks. Uh of symptom onset. Um So, in others said, another way, you know, in a patient who had resolved or had acute myocarditis and um and it completely resolved, um an MRI done, you know, you know, a few months afterwards could be completely normal. Um And so, um this is something to keep in mind when we're thinking about the timing of, of ordering tests and, and the test results impacting our, our, our, our diagnosis. Um And part of what plays into this perhaps is, is sometimes cardiac MRI is not as a access accessible. Um You know, we don't, you know, cardiac MRI is not done at every site. Um You wanna have a site, a center that does cardiac MRI and is very facile at interpreting results. Um and looking for things like cardi uh for uh looking at things like myocarditis and, and, and uh and, and uh and cardiomyopathies in general. And so, you know, I, and I've seen this before too where, you know, patients um may not be, may maybe in a place where they don't have um good access to cardiac MRI and they, they get an echocardiogram that shows LV dysfunction. Um And maybe they're given the diagnosis of non ischemic cardiomyopathy. They have ac and, and uh and uh they have no coronary artery disease. Um um um but they don't, don't, they do not end up getting a cardiac MRI in, in timely fashion perhaps because they don't have access to it. There's, there's not a, a cardiac um MRI locally. And um yeah, I mean, th th that's something that could potentially lead to um under diagnosis of, of something like myocarditis. Um This is, these are some other MRI images. Um um We've already shown some images but some other images of uh of a patient with uh acute myocarditis again showing if you can see this sort of brightness. Um This is the left ventricle. Th this is the MRI cross sectional short axis view with the left ventricle here, the right ventricle here and this is the interventricular septum. And um you can see sort of this, this band um here. Um this, this darker area here um at this interventricular septum that is late Galen enhancement. Um uh that is suggestive of scar fibrosis in a, in a myocarditis type pattern. Um And um you, you also see a similar area here. Um again, left ventricle, right ventricle. This is a short axis view. This is the infra lateral wall um uh l late Galen enhancement at the la infra lateral wall. These locations and the, the the locations of uh late galilean enhancement are fairly classic for myocarditis. All right. So now we'll move on to um uh myocarditis in the setting of COVID-19. So, um as, as we sort of talked about there, you know, it's not surprising to a lot of us that COVID-19 can trigger myocarditis and we don't, we're still trying to understand why or how that uh the the mechanism is. But there are multiple different um hypotheses. Um you know, oxygen supply demand mismatch and ischemia. Um you know, microvascular thrombosis um could be, you know, a culprit, certainly inflammation um is a bit is part of our understanding of, of myocarditis. And so, um as illustrated in this le lower right panel is, is when you have um you know, a SARS CO V two viral particle that you know binds to the cardiac myocyte. Um you know, that can trigger, you know, a cascade of events. Um much of which are uh inflammatory in nature. Um I remember during the pandemic, we, we saw and heard um about patients in the IC U was what we call cytokine storm where, you know, they, their inflammatory markers were up, you know, they were febrile. Um um they, they, you know, they had um you know, evidence of inflammation with, with uh elevated white blood cell counts. Um for example, um and uh we, we, we think that um you know, this uh this uh uh the, the, the binding of SARS COVID two to the heart can set off um um a cascade of events not just directly affecting or in infecting the cardiac myocyte, but also, you know, contributing to, you know, this inflammation, which is part of the disease process itself. So, so again, not just and uh and it's not just an infection problem, but it's also that, you know, subsequent in inflammatory response that that can be part of the disease. Um And so, you know, in, in, in uh patients with COVID-19, we saw uh, you know, a, a significant percentage of patients with myocarditis, COVID-19, myocarditis that had a fulminant presentation. Ie you know, you know, cardiogenic shock, heart failure, severe LV dysfunction. Um and they ended up having very poor outcomes or, or needing transplant. Um The, you know, these, these, these diagnoses of myocarditis may have been underestimated given that they, they would have um you know, multiorgan involvement, including the lungs and, and so this could have uh affected our ability to diagnose myocarditis in these um in these very, very ill patients. Um you know, another important thing to remember is that, you know, troponins in these patients with acute myocarditis correlate really with prognosis. Um you can have a patient with mild disease with a normal troponin. Um And so the absence of an elevated troponin does not rule this out. Now in, in hospitalized patients with pulmon and myocarditis, you know, inevitably, you know, they're all gonna have elevated remote troponins. Um um but uh in the outpatient setting, for example, um the troponin may not be, you know, don't, don't hang your hat on that troponin um in the outpatient setting in, in patients with mild mild disease. Um This is an another cartoon from, from uh uh that same paper. Um and I won't go into this in too much detail, but just wanted to kind of illustrate the, the, you know, the complexity of, of, you know, cellular mechanisms and how they may affect the clinical presentation of myocarditis. Um And so this is a cartoon of a mast cell which is a, which is a uh uh a white blood cell of myeloid lineage. And, and uh this the the the effect of SARS CO V two on the mast cell is thought to be an important part of, of the pathophysiology of myocarditis. Um So, you know, here, when you know, you see this on the lower left here, you see this SARS CO V two viral particle. Um you know, we've heard of the, the spike protein um and how, and, and that, and that's on the outside of the viral particle and how it binds to the ace two receptor on the um on on this particular cell. And that triggers uh uh a cascade of of events uh um including clotting factor, release inflammatory factors, re release il six il one histamines. Um Yeah, which, which can, can again be part of the, the the disease process and cause hemodynamic instability. Um And, and so this is thought to be a, a key part of the uh of the uh the disease process, not just the virus entering the cell, the virus does we think still directly infect the cell? And, and uh you know, cause cell death that way. Um But it's probably more complicated. Uh the disease process is probably more complicated than that. All right. So, moving on to, from COVID-19 to the COVID-19 vaccines and, and it's their relationship to myocarditis. So, um as we know, um you know, the MRN A, the messenger RN A vaccines have been most clearly correlated with um cases of myocarditis. So the MRN A vaccines, they contain modified MRN A that enlo encodes the that spike protein of the SARS COVID two virus. And so when you, you know, obviously, when you give that vaccine that, that uh that protein in the sorry, the MRN A that encodes that protein leads to the antibody to the spike protein. Um And that uh that antibody, you know, uh prevents binding of the virus to the ace two inhibitor uh ace two receptor. So, so that's the way the MRN A vaccines work. Um um I, I'll, I'll talk about this, I think in the next slide but uh the, the, the, the, the reasons why the vaccine, the MRN A vaccines can cause or lead to myocarditis still to be determined. We're still trying to figure that out. Um But what we've seen is that the highest risk of myocarditis is with uh the second dose or after the second dose of vaccine. And again, in young younger males. Um So the, I think the, the significance of this happening typically after the second vaccine is that, um, as you might expect, you know, after the first vaccine, um you haven't developed the antibodies yet. Uh you know, after that first vaccine, the antibodies have now been formed and then after the second vaccine dose, um then you have sort of an immune response, um uh that's already built in to lead to uh potentially lead to myocarditis, uh sort of that, that uh that reaction. So, symptoms of, of myocarditis after the vaccine typically occur, we saw typically occurred, you know, within anywhere from 3 to 11 days after, again after the second dose. And usually, you know, symptoms would be mild and transient. So I, I remember seeing, you know, a again after the vaccines came out, I would, I, I saw a, a good number of patients in the clinic with, with um you know, who would complain of some chest pain and, you know, they, they would be worried that they had myocarditis and, and, you know, II I think at, during those early times, you know, it was, it was, it was challenging to counsel them, you know, especially in, in, in the setting of, you know, these cases being, you know, these myocarditis cases after um vaccines being reported and patients would be wondering, oh, I shouldn't have gotten the vaccine. Um II, I would, I would and I still point them to the literature uh showing that the, the, the benefit of the vaccines um would really outweigh the very low risk of the vaccines in terms of myocarditis risk. Um And there's actually a very nice paper and I think the and Jack or, or Jamma, um actually doing that kind of risk benefit comparison if you're interested, you know, again showing that, you know, almost, you know, almost very clearly, you know, the benefit of the vaccines would well outweigh um uh the risk of developing myocarditis even in uh the young, young male uh population. Um So do keep that in mind. Um So I, I touched on this a little bit uh mechanism, possible mechanisms behind uh uh MRN A vaccine induced myocarditis, pericarditis. Um So, uh you know what we think potentially could be uh the culprit is the, you know, the spike protein of the virus. Um um um kind of mimicking um the cardiac myosin or the cardi cardiac myocyte uh uh receptor molecule. And so, basically causing um you know, the attack on your own on your own cells, an autoimmune reaction leading to uh myocarditis, um cytokine storm or sort of an inflammatory response uh from the vaccine itself. And it, it, it is, it is also a possible culprit. And then um the, the, the vehicle, the, the nanoparticle vehicle that um actually is the carrier for if you will, for the MRN A vaccine could also be uh something that triggers an autoimmune response leading to myocarditis. Um um It is interesting that the, the myocarditis cases after vaccine um occur in a very similar, tend to occur in a very similar demographic. Um um as the pre COVID and the COVID myocarditis patients ie you know, tend to happen more often in young, younger patients and in the male patients. Um So there may be a commonality uh to that uh because of, because of that. All right. So uh uh uh uh th that's a little bit about COVID-19, myocarditis and COVID-19 vaccine, myocarditis. And I'll now move on and touch a little bit about newer um fairly recent uh information that we have about certain cancer um treatments that can um trigger myocarditis. And so there are specific um immune modulating um uh treatments or medications called immune checkpoint inhibitors. Um We, we, you know, easily said checkpoint inhibitors. And so these are actually monoclonal antibodies that are cancer treatments that target um um host immune um uh regulation receptors. And I'll, I'll show you a uh a picture of this in the next slide I think or, or two slides later, which illustrates this. Um basically these antibodies um uh are designed to target the host immune um response to trigger the host's immune system to, you know, kill the, the, the cancer cells um specifically. And so, um these uh these uh treatments have been associated with development of myocarditis and the mechanism behind this. Again, very similar to maybe the vaccine um concept is a shared, a, a shared um antigen or uh, yeah AAA shared uh um, uh antigen between the tumor and the cardiac myocyte. Um, and uh this type of myocarditis is seem to be very, quite uncommon, uh uncommon but, you know, the patients can have very high mortality. Um, I mean, even in some papers up to 50% um these cases of myocarditis typically present within the 1st 12 months after initiating therapy. Um, and these therapies, you know, I see, I'm not a, I'm not an oncologist, but uh I see typically that these injection, these are injection infusion medicines that are given once every few, few weeks or a couple of times a month. And so, you know, keep that in mind if you have um oncology, patients, um getting treatment with uh a checkpoint inhibitor. Um you know, this, the, you know, they can develop um symptoms of myocarditis, look out for symptoms of myocarditis. Um um you know, even one or two months after after initiation of therapy. Um and the treatment typically is stopping the, the therapy and, and using steroids, um predniSONE or solum Berol. Um And so, so these are, this is a list of, um I, I think a fairly current list of FDA approved um um checkpoint inhibitors. And so, um um one of the, you know, and they're used for a variety of different cancers, including lung cancer, melanoma, skin cancers, um et cetera. Um The, the ones that I've seen most commonly used Pembrolizumab. Uh I, I hear it. Uh Pembroke, uh some of the oncologists say so. So Pem bro and uh Nivolumab um are also um um are, are some of the more commonly used um checkpoint inhibitors. So, so again, something to think about if you have patients on these medications and they have symptoms, um kind of think about um myocarditis. Um Yeah. So this is the cartoon that I was referring to. So on the left, um This is a cartoon that this is a tumor cell here on the top and then on the bottom, this is a T cell and this is a specific um um uh situation where you have a checkpoint protein. Um you know, with PD one binding to PDL one and this binding of the checkpoint protein um promotes a negative regulation sort of an off signal so that the T cell does not attack that tumor cell. Um So that's on the left panel. Um on the right panel, this is the actual um uh immune therapy, the checkpoint inhibitor and it's here illustrated as this sort of red triangle here. So this is a, this is a, this is a checkpoint inhibitor that binds to the PD one of the T cell. And um this is, this is a, this is a, this binds on the tumor cell and this turns off the off signal so that now the T cell is um kind of activated to now cause and initiate tumor cell death and, and lice the the the cancer cell. So that's a little bit about how the checkpoint inhibitors work. And you know, potentially the the the the the the mechanism of myocarditis um in, in, in this treatment may be related to. Again, you know how this receptor may be ss very similar um to, you know, something on the normal um cardiomyocyte. Um This is a, a sample EKG or ECG of a patient with immune checkpoint inhibitor myocarditis. So, so the, you know, the top panel is the EKG of this patient before receiving the treatment. Um and es essentially normal PR interval, um um pretty benign, fairly benign looking ecg you know, maybe uh incomplete right bundle grant block with the, with the, with the axis deviation. Um But then on the bottom, I'll point out it's nicely pointed out with the, with the uh with the circles and the and the squares here. But uh this is a patient who is, this is the same patient who has received um immune checkpoint inhibitor treatment um and has developed chest pain and evidence of myocarditis on imaging. And so um his EKG shows a prolongation in the PR interval um and PV CS. So, so these are signs, well, I mean, the patient already had the diagnosis but, but these are signs that this patient could have, you know, cardiac arrhythmia as part of their myocarditis presentation or has has a cardiac arrhythmia that could progress to say, uh complete heart block um with their, with their myocarditis. Um I uh I have two more slides and then we'll, we'll, we'll stop for questions. So, so, you know, my card, we talked a lot about, you know, the basics and of myocarditis and what we know more about myocarditis um management. Um uh this general management. Uh We've, we've, we continue to use um in patients who have l left ventricular dysfunction and heart failure, we use standard heart failure treatment. Um We support them hemodynamically. Um if they're in the hospital and need pressure support, you know, that's what, that's what they get. And uh eventually, you know, if they're sick enough, they had in cases of fin and myocarditis, they may need um you know, um uh mechanical support, um ventricular assist devices. Um um and you know, emo um and uh heart transplant. Um um these are, these are, these are very, these can be very sick patients and, and um require very, very um specialized care in an IC U. Um in terms of arrhythmia treatment, you know, the specific treatment aside from sort of hemodynamic support is, is uh you know, if they have ventricular tachycardia, sudden cardiac death. The question being, you know, did they need a defibrillator? And you know, this is obviously a, a decision that's, that's weighed um uh with risk with risks and benefits. And, you know, each specific case has, has its own details. But, you know, in general, you know, you know, since myocarditis is AAA disease that can resolve, um you know, we don't often jump to implanting a defibrillator. Um Unless, you know, if, unless we know that there's some chronicity to the left ventricular dysfunction and, and, and uh or, or if the patient's continuing to have VT um um um throughout their hospital course, then, you know, these, these might be reasons to, to implant a defibrillator, uh know that uh non steroidal anti inflammatory uh uh agents are not beneficial for myocarditis. So, so, you know, different from pericarditis, um nsaids are not beneficial for, for myocarditis patients. Um and also, um remember about uh patients with myocarditis and their need for physical activity restriction. There is data showing that um you know, patients who do not have restriction in their physical activity after a diagnosis of myocarditis that can worsen their disease. And so particularly, um in patients who do athletics, um you know, as we talked about young males, um being, you know, more, some of the more um um more frequent uh um populations to have myocarditis, you know, they, they might be, you know, athletes. Um but if they have myocarditis, the, the standard of care really is at least um 3 to 6 months of, of abstaining from, from significant athletics and comp certainly competitive athletics um uh for, for their benefit. All right. Um Last slide. Oh, sorry. I think this is my second to last slide. So, so, you know, I think I won't spend too much on this. There, there are lots of, you know, potential treatments. Um In addition to what I just mentioned about, um you know, about uh general treatment for myocarditis, um some of these are quite new and there's no, you know, real strong randomized control trials to, to uh show that these are the, that these are the the treatments to use. Um But um you know, oftentimes um if you have a pa a very critically ill patient in this, in the IC U and they're not responding to steroids, they're, they're not uh getting better, you know, you know, sometimes, you know, we try agents that um yeah may not be proven but you know, we're, we're basically using a Hail Mary type of approach. So, so um even though not super data driven, you know, il one inhibitors or Jack two inhibitors, um Ivig Ha has been used. Um these are, these are again, you know, use on a case to case basis and only done really in the IC U with, with uh with uh with a team that is familiar with these, the use of these agents. Um but def definitely not uh uh not a clear standard of care when it comes to um these types of treatments. So this is sort of a summary uh summary graph or pictorial that I got from a paper um, again, sort of illustrating, um, you know, some of the work up that we do, um, and um, uh kind of stratifying it, um uh according to higher risk patients on the left and lowest risk patients on the right and the blue panel. And so, you know, if you're having, if you have a patient in your clinic who has chest pain and you're concerned about um, uh myocarditis, but this is a low, you know, you think a low risk patient, you know, they're not in heart failure, you know, they're in sinus rhythm, they're not having arrhythmias, you do an echo, their ef is normal. Um, you know, you, you know, oftentimes what is done is, you know, well, sending it to, sending this patient to a cardiologist would certainly be reasonable. Um, and getting, eventually getting a ca a cardiac MRI um would, would be, um, probably one of the next steps versus, you know, a higher, higher risk patient who you're probably not seeing in the office. Um, but someone in the hospital who is in shock or in heart failure, these, the, you know, these patients definitely should be in a, you know, a, a specialized um center uh um used to dealing with, you know, patients with critically ill um with critical illness uh and cardiac illness. And, you know, they, they, they oftentimes do get um biopsies to um for, for confirmation of diagnosis. And part of the reason why, why biopsy may be helpful in those situations. Is, you know, the the treatment can be tailored based on the biopsy results. For example, if you have giant cell myocarditis on, on a biopsy sample, then um you know, they're treated differently than say a patient with COVID um uh COVID-19 myocarditis, which you know, they would have, you know, they would, the COVID-19 myocarditis patient probably would would, would be more of a supportive care type of situation. Whereas a giant cell myocarditis patient, you're using immunomodulators steroids um um to go for treatment. Um, those are my slides and I'm have, oh, it's one o'clock. So I'm happy to take questions.
