Circulation August 10, 2021 Issue

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.