Aug 9, 2021
This week's episode features a panel discussion in regard to Covid-19. Please join authors Kathryn Larson, Christopher deFilippi, James de Lemos, and Biykem Bozkurt as they discuss their articles regarding temporary myocarditis and Covid-19 vaccination.
Dr. Carolyn Lam:
Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.
Dr. Greg Hundley:
And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia.
Dr. Greg Hundley:
Carolyn, this week, oh my goodness. It's a forum, almost a triple or quadruple feature, and you know what we're going to be discussing? COVID-19 vaccinations and their relationship potentially to myocarditis. We're going to have our associate editors and our deputy editor involved, be really interesting. But before we get to that, how about we start in with the papers in the issue. Would you like to go first?
Dr. Carolyn Lam:
Absolutely. And my first paper is so interesting. It identified a novel underlying mechanism of graft arteriopathy, or otherwise known as coronary allograft vasculopathy, a devastating development of heart transplant in which arterial intimal thickening limits coronary blood flow and could lead to transplant failure.
Dr. Greg Hundley:
Oh wow, Carolyn. So, what did they find?
Dr. Carolyn Lam:
Well, this was Dr. Martin from Yale Cardiovascular Research Center and colleagues. What they did is they used both human coronary allograft vasculopathy and renal transplant samples as well as murine models, basically, and found that TET methylcytosine dioxygenase 2, or TET2, is a critical negative regulator of vascular smooth muscle cell apoptosis in graft arteriopathy and vascular injury. Enhancing smooth muscle TET2 activity with a high dose of ascorbic acid rescued donor vascular smooth muscle cells apoptosis and intimal thickening in murine transplant vasculopathy. Furthermore, TET2 expression and activity were repressed in arterial vascular smooth muscle cells in human and mouse graft arteriopathy compared to controls.
Dr. Carolyn Lam:
Interferon gamma signaling in vascular smooth muscle cells resulted in TET2 repression. Preventing donor vascular smooth muscle cell apoptosis with high dose ascorbic acid may therefore represent a safe and cost-effective therapeutic strategy for limiting graft arteriopathy in patients undergoing solid organ transplant. Neat, huh?
Dr. Greg Hundley:
You bet, Carolyn. Really an interesting article on limiting graft arteriopathy.
Dr. Greg Hundley:
Well, Carolyn, my next paper comes to us from Dr. Greg Stone and colleagues at the Cardiovascular Research Foundation. It involves the randomized COAPT trial. Remember that in the COAPT trial, there were 614 heart failure patients with 3+ or 4+ secondary mitral regurgitation and had trans-catheter mitral valve repair with the MitraClip, reduced mitral regurgitation, heart failure hospitalizations and mortality as well as improving quality of life compared with guideline directed medical therapy alone. So the authors here, Carolyn, sought to examine the prognostic relationship between mitral regurgitation reduction and outcomes in trans-catheter mitral valve repair versus guideline directed medical therapy alone.
Dr. Carolyn Lam:
Wow, okay. So, what did they find, Greg?
Dr. Greg Hundley:
Right, Carolyn. So, among patients with heart failure and severe, grade 3+ or 4+ secondary mitral regurgitation randomized to trans-catheter mitral valve repair with the MitraClip versus guideline directed medical therapy, the reduction of MR to 2+ was strongly associated with subsequent two year freedom from death and heart failure hospitalization and improved quality of life regardless of whether this reduction to 2+ MR was achieved by trans-catheter clip or guideline directed medical therapy alone. And the improvement in long term prognosis was similar after this mitral regurgitation reduction to grade 2+ compared with grade 0 or 1+ in both arms, although the mitral regurgitation reduction was a little more durable over time after the trans-catheter mitral clip.
Dr. Greg Hundley:
So Carolyn, the take-home message is that substantial benefits are realized even if mitral regurgitation is reduced to only 2+.
Dr. Carolyn Lam:
Nice, Greg. Thanks.
Dr. Carolyn Lam:
Now, this next paper, oh, close to my heart. We know that individuals of South Asian ancestry actually represent 23% of the global population, corresponding to 1.8 billion people, and that they have a substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. However, what is the magnitude of that enhanced risk, the extent to which it is captured by existing risk estimators, and what are its potential mechanisms?
Dr. Carolyn Lam:
This was studied in this beautiful paper. Dr. Khera from Massachusetts General Hospital and colleagues used data from the large UK Biobank prospective cohort study to investigate the relationship between South Asian ancestry and incident atherosclerotic cardiovascular disease within the context of contemporary medical care. Their findings confirmed an approximate doubling of atherosclerotic cardiovascular disease risk among South Asian compared with European individuals that was not captured by the pooled cohort equations. The higher risk of atherosclerotic cardiovascular disease persisted despite adjustment for a broad range of potential clinical, anthropometric, and lifestyle mediators. Hypertension, diabetes, and central adiposity explain a greater proportion of risk of atherosclerotic cardiovascular disease in South Asian compared with European individuals.
Dr. Greg Hundley:
Wow, Carolyn. So, a lot of data here. How do we take all this and put it together clinically?
Dr. Carolyn Lam:
Well, the results confirm and extend the current guidelines that consider South Asian ancestry a risk-enhancing factor in assessing future risk for atherosclerotic cardiovascular disease. Residual risks that persisted after accounting for a range of potential mediators may relate to differences in social determinants of health, unmeasured risk factors and genetics and so on, that this warrants further investigation. Whether a targeted intervention can attenuate the outsized impact of diabetes or central adiposity among South Asian individuals also warrants further attention.
Dr. Carolyn Lam:
This is accompanied by a beautiful editorial entitled The South Asian Enigma: Solving a Puzzle of Global Importance, love that, from Drs. Kandula from Northwestern University Medical Center and Kanaya from University of California San Francisco.
Dr. Greg Hundley:
Very nice, Carolyn. I just want you to know, after being quizzed last week on phospholamban, I went and did a little bit of studying, okay? So I get to bring to you, Carolyn, this week, a paper on phospholamban. But I'm going to spare you from the quiz.
Dr. Greg Hundley:
All right.
Dr. Carolyn Lam:
Yay!
Dr. Greg Hundley:
This comes to us from Professor Fadi Akar from Yale University. Carolyn, arginine 14 deletion is the calcium regulatory protein phospholamban, so hPLN R14 deletion. It has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy, and mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling really remain unclear.
Dr. Carolyn Lam:
Interesting, Greg. So, what did they find?
Dr. Greg Hundley:
Right, Carolyn. Adverse electrophysiological remodeling was evident in the absence of significant structural hemodynamic changes, and the R14 deletion hearts exhibited increased arrhythmia susceptibility compared to their wild-type counterparts. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to beta-adrenergic stimulation. A steep repolarization gradient at the LV/RV interface provided the substrate for inter-ventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. And then once sustained, these circuits evolved into high frequency rotors, which in their majority were pinned to the right ventricle. Importantly, these rotors exhibited unique spatio-temporal dynamics that promoted their increased stability in the R14 deletion compared to the wild-type hearts.
Dr. Greg Hundley:
So Carolyn, in summary, this research found the crucial role of primary electrical remodeling caused by the hPLN R14 deletion mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of the PLN R14 deletion induced a cardiomyopathy.
Dr. Carolyn Lam:
Oh, and ties up very nicely about how we mentioned that this dilated cardiomyopathy is associated with lots of ventricular arrhythmias that we discussed last week. Really cool.
Dr. Carolyn Lam:
Well, let's do a little tour around what else there is in today's issue. Tracy Hampton presents from the literature discussing how excessive exercise may damage mitochondria and impair glucose control in a publication from Cell Metabolism. Data on an oral antisense oligonucleotide for PCSK9 inhibition was published in Science Translational Medicine.
Dr. Carolyn Lam:
And there's a paper on structuring clinical text with AI. How very interesting, published in Patterns. There's an On My Mind paper by Dr. Berger on summoning strength to question the placebo in reducing.
Dr. Greg Hundley:
Right, Carolyn. Also in the mail bag, there is a reply to the Quintao and Cazita from Professor Brunham entitled High-Density Lipoprotein Cholesteryl Ester Transfer Protein and Sepsis. And then finally, from Dr. Goldstein, an ECG challenge. Does this ischemia pattern look right?
Dr. Greg Hundley:
Well, Carolyn, this is going to be a really interesting feature forum discussion today on COVID-19 vaccinations and myocarditis. How about we get on to that discussion?
Dr. Carolyn Lam:
Yep. A really important issue now. Yup, let's go.
Dr. Greg Hundley:
Welcome, listeners. We have a very exciting, really series, of feature discussions. We're going to call it a forum, and focusing on COVID-19 vaccine associated myocarditis. We really have four manuscripts to discuss today. We have Dr. Kathryn Larson from the Mayo Clinic in Rochester. We have another author, Dr. Chris deFilippi from Inova Health, really in the Washington DC metro area. We have our executive editor, Dr. James deLemos from UT Southwestern in Dallas, Texas. And then also one of our senior associate editors, Dr. Biykem Bozkurt from Baylor College of Medicine in Houston, Texas. Welcome to everyone.
Dr. Greg Hundley:
Well, first, listeners, we're going to start with Dr. Larson. So, Kathryn, can you tell us a little bit about the background and the hypothesis that you were testing in your research project, and then a little bit about your study design and what were the results of your study?
Dr. Kathryn Larson:
Absolutely. Well, first off, thank you so much for having me, Greg. It's a pleasure to be here and in such good company. My study really grew out of a clinical interest in a number of patients that had presented to our institution and other institutions that we had been in discussion with of really young male patients with no significant past medical history who were coming in two to three days after receiving their COVID vaccines, most often the second dose, and presenting with laboratory and clinical findings consistent with myocarditis. I think in a lot of arteriosity and what the course of their illness may be and what the best course of treatment may be, that really drove our hypothesis to try and describe other cases that were coming up and that we had heard about from a lot of our colleagues around the country and around the world.
Dr. Kathryn Larson:
Our paper really grew out of a case series of eight patients, and they're from the United States and from Italy, and they're of eight patients who were diagnosed with laboratory and clinical and imaging findings consistent with myocarditis after receiving their COVID-19 vaccines. Our patients had received either the Pfizer BioNTech or the Moderna vaccines, the mRNA vaccines. Really, only two of our patients had previously been infected with COVID at all, and so most of these patients were coming in with really no relevant medical history. They were really young in age, between 21 and 56 years old, and basically all patients except for one developed their symptoms after receiving the second dose of the vaccine.
Dr. Kathryn Larson:
The timeline was generally about two to three days after that dose and was often accompanied by other symptoms which we have seen and heard about things like myalgias, subjective fevers, chills, and kind of a general malaise. They presented really with very typical features of myocarditis, chest pain, one of the patients had a more pleuritic type of chest pain, and had ECG changes, troponin elevations, elevated inflammatory markers, and most importantly cardiac MRI findings that were significant and really diagnostic of myocarditis.
Dr. Kathryn Larson:
There was a good amount of investigation into other potential causes and none other identified in any of those eight patients. All thankfully had a relatively unremarkable course clinically and all are currently doing very well. There was mild reductions in LV function, no clinically significant heart failure, and at last known contact, those patients really had recovery of LV function and are essentially back to baseline.
Dr. Greg Hundley:
Excellent. Well, listeners, we're going to move to another part of the country, and again, Dr. Chris deFilippi is in the Washington metro area. Chris, you also have a case series. Can you describe for us what you were looking at with your study, and then what were your study results?
Dr. Chris deFilippi:
Greg, first, thank you for having me here today. As a regular listener to Circulation on the Run, it's really a privilege to actually be able to participate and contribute to it. First, I would have to say was a little bit of serendipity. We recognized one case out of the ordinary with respect to suspected myocarditis in early March, and given our location around Washington DC, some of our faculty were former active military and serve in the reserves and one returned and said, "The military is beginning to find a small series of cases."
Dr. Chris deFilippi:
We've worked hard within our academically oriented independent health system to develop a research clinical trials network, and we called upon our cardiologists and cases started coming forward actually fairly rapidly, drawing upon five hospitals in our network. Combining our efforts with UT Southwestern, we identified seven individuals. They were all men or young adults in their 20s and 30s. Six out of seven had received the mRNA vaccines. Most of them had developed symptoms between three to seven days after their second vaccination.
Dr. Chris deFilippi:
Very similar to Kathryn's presentation, we did an extensive evaluation, of course including advanced imaging with MRI using the Lake Louise criteria, but also did a lot of serologic measurements. I think it was remarkable that troponin values using still a conventional assay ranged from mild elevations, 0.34 to as high as 44 milligrams per milliliter.
Dr. Chris deFilippi:
All patients fortunately had resolution of symptoms within several days and returned back to normal life and then all return follow-ups seemed to remain symptom-free. Again, we looked for multiple other etiologies including autoimmune disease, other respiratory infections, and these were all effectively negative.
Dr. Greg Hundley:
Very nice. Well now, listeners, we're going to head south, down to Dallas, Texas and bring in Dr. James deLemos. James, you also have a case report and did some extensive study, I believe, in your patient in terms of investigating perhaps mechanisms. Could you share with us your study and some of your findings?
Dr. James deLemos:
Yeah. Thanks, Greg. Ours was like Kathryn and Chris's experience, purely serendipitous. I was on service in late January at our university hospital and we had a case that came in three days after receiving the Moderna vaccine with what appeared to be clearly myocarditis in temporal association with the vaccine. At that time, we reported it to the CDC, but there was really not much, if anything, and so what we decided to do was pull together a translational team. We brought together clinical pathologists, immunologists, infectious disease experts, and a panel of folks to think about how we might get at a potential mechanism, obviously in a highly exploratory fashion because this was one case and at this point we really didn't know whether this was a true causal association or just circumstance.
Dr. James deLemos:
What we did was really a broad exploratory analysis, comparing our index case with a number of vaccinated controls, COVID infected controls, and normal controls. We did autoantibody panels, cytokine panels. We looked at flow cytometry for cell fractions, and really tried to see if there was a signature for our case that distinguished it from these other control groups.
Dr. James deLemos:
I think one important thing we didn't see was an exuberant or over exuberant response in terms of the spike antibody. That was also not seen in several other cases from Chris and Kathryn. The antibody response seemed to be in the normal range of what would be expected after the vaccine. We also didn't see broad spread inflammation in our case compared to controls. There were several cytokines that were upregulated, some of which have been reported in myocarditis, and there were some natural killer cell subsets that would seem to be upregulated, and then several autoantibodies as well that have been reported in myocarditis. But interestingly, none of the poor prognosis autoantibodies that had been reported, which may in part, we think, explain why these cases seem to be doing quite well.
Dr. James deLemos:
I'd emphasize it's one case, so we recognize this is purely exploratory and hopefully will set the stage for other people as they try to investigate this in more depth.
Dr. Greg Hundley:
Thank you, James. Well, Biykem, you've been spending a large segment of time, the last year, really year and a half, trying to put together for us at the American Heart Association what may be operative in these patients receiving these vaccines, and also really studying COVID-19. It sounds like what we're hearing amongst all three of these, young men, really a myocarditis that develops after the second vaccine. We have typically elevated troponins, there's MRI findings. You've put together a review. Maybe you could start to share with us what have you learned over this past year and a half?
Dr. Biykem Bozkurt:
Thank you, Greg. As my colleagues have alluded to, the characterization of the presentation is pretty concordant. What I did in the review was to review all the case reports and case series published to date, which summed up to 61 cases. Additionally, I looked at what has been reported by the Vaccine Adverse Event Reporting System by the CDC and their internal analyses, and also looked at the reports that came from Israel as well as the US military, which is a large cohort and population base reporting.
Dr. Biykem Bozkurt:
The messages for the clinicians, number one, the presentation in most of these reports have been pretty unified in the sense that most patients presented day two or day three after the second dose of mRNA vaccination. Secondly, most if not all had cardiac troponin elevation along with chest pain on presentation. The majority of the patients, more than 90, 95 in the case series, had EKG abnormality, usually with ST elevation. When we're to examine the echo findings, about two thirds or sometimes in the case series about 40% of abnormalities and only a small percentage had LV systolic dysfunction with EF less than 50.
Dr. Biykem Bozkurt:
When done as was the case in all the case series and case reports, cardiac MRI was always abnormal. They were very self-limited. Important concepts are, these were very self-limited cases. All of them recovered and were discharged and had resolution of their symptoms, biomarker findings as well as imaging findings.
Dr. Biykem Bozkurt:
Now, let's look at the benefits versus risk concept that was examined at the CDC level. The current reporting in the VAERS system, the Vaccine Adverse Event Reporting System, is about 12.6 cases per million doses of vaccination. This is after 300 million doses being given in the US and about 170 million individuals being vaccinated in the US. Of those, when compared to what we have been expecting in the population, there appears to be a temporal association that the CDC has confirmed. If we were to look at the risk versus benefits ratios, it's very clear that COVID-19 is a deadly disease. It results in mortality even amongst the younger population, somewhere at the order of 0.1 to 1% per 100,000 people being infected. So for 12 to 39 years old, where the myocarditis risk is felt to be higher, still we need to keep in mind, that risk is very low. 12 per million doses, compared to about 0.1 to 1 death for about 100,000 infections.
Dr. Biykem Bozkurt:
And of course, if we were to add the number of hospitalizations, ICU stays, cardiac involvement, which we know is seen in about 12 to 20% of hospitalized patients by cardiac troponin elevation, as well as multisystem inflammatory syndrome that is seen in young populations, the benefits significantly outweigh the risks. In terms of mechanisms which James has alluded to, the things that are coming as potential signals or hypothesized mechanisms include the following. There could be molecular mimicry between the spike protein and the self-antigens. Currently, that experimental data, antibodies against spike protein have been reported to cross react with human proteins including alpha myogen. Other mechanisms could be vaccine and it making a response triggering a pre-existing dysregulated immunopathological pathway in predisposed patients. But mind you, we don't right now have a pattern of who's predisposed to myocarditis. It doesn't look like comorbidities as we have seen with COVID-19 infection.
Dr. Biykem Bozkurt:
And in James' case, there was no predisposition to cardiomyopathy identified by a gene variant that are known to be associated, so those were negative in the case reports that James had mentioned. There was increased frequency of autoantibodies in that case report that James had published. Again, this may be in reaction to the inflammation or injury rather than being the cause. It may be the outcome, but still it raises a concern whether autoantibody formation is one of the mechanisms.
Dr. Biykem Bozkurt:
Male predisposition is a known risk for myocarditis. We've known this even before the vaccine related myocarditis cases. In the experimental as well as population based studies in the past, young males have a higher predisposition than females or older age, and it's thought to be due to the differences related to sex hormones, especially testosterone, being pro-inflammatory. But of course, in the passive vaccine adverse event reporting, we also do know that the chest pain presentation did not appear to be as different among males compared to females and the imaging and studies were done in less frequency in females, so there may be also a bias toward work-up in females which needs to be further examined.
Dr. Biykem Bozkurt:
The most important message we'd like to put out there is the benefits highly outweigh the risks, but there needs to be recognition that there is such a risk for clinicians, and definitely do an appropriate work-up for patients presenting with chest pain to the emergency room or to the clinical setting for an appropriate work-up to be carried out including EKG, cardiac troponin in all patients, followed by imaging, such as cardiac MRI and/or other imaging as necessary depending on the symptomatology, the age, as well as the findings on the troponin and EKG. And cardiology moment is essential for those ones who are diagnosed with myocarditis. The treatment strategies in the case reports range all the way from non-steroidal colchicine to IV steroids to intravenous immunoglobulin. Probably the way to approach these cases is if it's very self-limited with resolution of symptoms and biomarkers within two or three days, they may not need to resort to very intensive therapy, but if the case is with unrelenting symptoms, persistent biomarker abnormality, an imaging finding higher level of intense geo-treatment with intravenous steroids or IV immunoglobulin may be considered.
Dr. Biykem Bozkurt:
So far in the published reports, there have not been any bad outcomes such as death and/or requirement for mechanical circulatory support, but again, further research is needed.
Dr. Greg Hundley:
Very nice, Biykem. Well, listeners, we're going to go back through our authors and just really quickly, Kathryn, Chris, James, Biykem, what study, maybe in 15 seconds, do you think might need to be performed next in this sphere of research? And then second, what's the one point that you think we ought to emphasize as we close out going forward? So, both questions for each author. Kathryn, we'll start with you.
Dr. Kathryn Larson:
Okay, cool. I think I'll bring a little bit of an imaging bias as that's my personal interest. I'd really like to see a lot of the data that's already out there from these patients both at their baseline studies, and I'd really like to see their follow-up studies in terms of what happens to things like LV function and in terms of their MRI findings. I think that could be really helpful given the amount of weight that imaging has in the diagnosis of these patients.
Dr. Kathryn Larson:
I think the biggest take-away for me in a lot of these discussions that we were having is, these are very rare issues and incidents when patients are presenting with these, and I think the vast majority of the information we have at hand is that these are self limited, there's good recovery of any decline in LV function, and that I think overall the clinical course is favorable.
Dr. Greg Hundley:
Very nice. Chris?
Dr. Chris deFilippi:
First, I shouldn't be promoting my colleague's work, but I've got to say that Biykem's review was terrific. I know I did a lot of background reading in this case presentation. I've gone through that review a couple times and it's clearly, I think, helped my thinking on this topic. As Biykem mentions in that review, the recording of myocarditis can have a number of biases either under or over reporting, basically what's available in the public and what sort of people are thinking about. I think looking at it from a population health standpoint, the risk benefits are so favorable for the benefits of vaccination. We knew that even a month ago, we know that even more today. But I think it would be great to get an understanding, recognizing that there may be cases of unrecognized myocarditis, myocardial fibrosis, at a population level in what we would assume would generally be very healthy, young adult males, do we see more cardiac related hospitalizations over time? Do we see more sudden death? I think we should just affirm that, hopefully we can affirm that isn't the case and keep moving forward.
Dr. Chris deFilippi:
That being said, I'm still really a big advocate for vaccination and the benefits of vaccination combined with these very small risks.
Dr. Greg Hundley:
Very nice. James?
Dr. James deLemos:
I'd say really two avenues for research. I'd echo Kathryn's point that we need longer term follow-up data for patients that have this syndrome. To do that we're going to have to collaborate, because each of us individually see very few cases, because fortunately this is rare, and we're going to need registries that look at longer term follow-up of patients with vaccine associated myocarditis. And then really getting to Chris' point on the front end, I think that's what's needed are prospective studies measuring high sensitivity troponin and cardiac MRI in younger individuals who get vaccinated, so we study them not once they get the disease, but trying to determine whether there might be even less severe versions of myocardial injury that are occurring after the vaccine and try to understand why that's the case, because mRNA vaccines are here to stay. They're remarkable advances. And let's understand what this apparently self limited myocarditis is all about.
Dr. James deLemos:
The take-home message I'd echo is that this is important and all of us even had angst about recording and talking about this, because we don't want this ever to be misconstrued to suggest that these vaccines, which are absolutely remarkable, don't have a favorable risk benefit, even for our cardiac patients. These data in no way affect the safety and efficacy of the vaccine, even in people with underlying cardiac disease, who are some of the ones that have the greatest priority to get vaccinated.
Dr. Greg Hundley:
And finally, Biykem.
Dr. Biykem Bozkurt:
I think I echo all my colleagues' sentiments in the necessity for prospective and imaging and biomarker. The way to do that, as James alluded to, is we should right now develop a consortium for a registry, and we should have a bioregistry. I would urge us to not solely consider it for vaccine related entity, but also COVID-19. So I think we need to straddle the whole concept of COVID-19 itself, the infection plus the vaccinated individuals and follow them in a prospective manner with the known biomarkers, the cardiac biomarkers as well as imaging, but also the thing that is lacking right now is to characterize them with a specific immune cell populations as to what is rising, what kind of response we've seen, with the changes that we're seeing in males and others, and capture further mechanistics, perhaps signaling. Quite a few of this phenotyping is needed in these individuals as well as perhaps a genotyping characterization and maybe a tissue characterization.
Dr. Biykem Bozkurt:
I think the consortium will need to entail pathologies as well as immunopathology along with biomarkers and imaging. And of course, prospectively following these individuals. As was done in certain other vaccines in the past may give us a totally different signal and prevalence.
Dr. Biykem Bozkurt:
Take-home message, I fully agree. Being able to get a message of the risk is low compared to benefit. While we're calling for, the necessity for further research is a delicate balance of what the scientists have to straddle. Yes, the vaccine is very safe. It's been shown in numerous, several randomized clinical trials. Current data actually validates that because it's a few cases in millions of doses of the safest vaccine. But for those very few cases, for those very few cases we need to be on the alert and treat them appropriately and not miss those diagnoses.
Dr. Biykem Bozkurt:
One other message I'm going to share is the rapidly evolving conceptualization of myocarditis. The lymphocytic myocarditis concept that historically was the gold standard characterization of myocarditis with other viruses is, I think, rapidly changing now with the recognition of what we saw with COVID-19 itself, as well as now with the vaccine. It does not seem to be the classical characterization of myocarditis, so again, understanding of myocardial injury, cardiomyocyte injury is now a continuum beyond what we used to call the path to MI and injury, now straddling all the way to a concept of injury that is much different than the lymphocytic myocarditis we've seen with other viruses, which we need to embrace.
Dr. Greg Hundley:
Very nice. Well, listeners, we want to thank Dr. Kathryn Lawson, Dr. Chris deFilippi, Dr. James deLemos, Dr. Biykem Bozkurt, for this wonderful forum discussion on COVID-19 vaccine associated myocarditis.
Dr. Greg Hundley:
Well, thank you so much and on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run.
Dr. Greg Hundley:
This program is copyright of the American Heart Association 2021.
Dr. Greg Hundley:
The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAJournals.org.