Circulation September 28, 2021 Issue

This week's episode features a panel discussion. Please
join author Harmony Reynolds, editorialist David Newby, and
Associate Editors Nicholas Mills and Sandeep Das as they discuss
the articles "Natural History of Patients with Ischemia and No
Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study,
"Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease
and Ischemia Severity," and editorial "Forget ischemia, it's all
about the plaque."


Dr. Greg Hundley:


Welcome listeners to this week's, September 28th, issue of
Circulation on the Run. And I'm Dr. Greg Hundley, Director of the
Poly Heart Center at VCU Health in Richmond, Virginia, and
associate editor at Circulation. And this week, listeners, we
have an outstanding feature discussion. It's actually forum where
we're going to discuss from Dr. Reynolds two papers pertaining to
the ischemia trial. One looking really at the functional
importance of stress testing, the other looking at the anatomical
importance of cardiac CT scanning. We're going to have two of the
associate editors along with Dr. Reynolds, each that handled the
two papers and also a guest editorialist that will help put the
entire paper together. Well, before we get to that, we're going
to start and review some of the other papers in this issue. And
let's grab a cup of coffee and get started.


Dr. Greg Hundley:


The first comes to us from Dr. Maliheh Nazari-Jahantigh from
Ludwig Maximilian University in Munich, Germany, and it pertains
to atherosclerotic plaque rupture. So the necrotic core of an
atherosclerotic plaque is partly formed by ineffective
efferocytosis, which increases the risk of an atherosclerotic
plaque rupture. And in cell biology, efferocytosis comes from the
Latin word effero, which means to take to the grave or to bury.
And it's really the process by which apoptotic cells are removed
by phagocytic cells. And so therefore, it can be regarded as the
burying of "dead cells." Now MicroRNAs contribute to necrotic
core formation by regulating efferocytosis as well as macrophage
apoptosis. We also know that atherosclerotic plaque rupture
occurs at an increased frequency in the early morning, indicating
that diurnal changes occur in plaque vulnerability. Now all those
circadian rhythms play a role in atherosclerosis, the molecular
clock output pathways that control plaque composition and rupture
susceptibility are unclear.


Dr. Greg Hundley:


And so these authors investigated this phenomenon. And what they
found, interestingly, their results suggest that the molecular
clock in atherosclerotic lesions induces a diurnal rhythm of
apoptosis regulated by circadian Mer 21 expression in macrophages
that is not matched by efferocytosis, and thereby increasing the
size of the necrotic core of these plaques. So clinically, the
implications are that a macrophage death clock controlled by mer
21 may enhance lesion growth and susceptibility to plaque rupture
indicating that the molecular clock can have detrimental effects
under pathologic conditions. And additionally, the molecular
clock in lesional macrophages may contribute to the circadian
pattern of myocardial infarction, which could be a target for
preventive measures to limit the mismatch between apoptosis and
efferocytosis and thus reduce plaque vulnerability in the early
morning.


Dr. Greg Hundley:


Well, our second paper comes to us also from the world of
preclinical science, and it's from Professor Thomas Braun from
the Max Planck Institute for heart and lung research. And this
particular paper pertains to pulmonary hypertension. And as we
know, pulmonary hypertension and chronic obstructive pulmonary
disease, or COPD, originate from a complex interplay of
environmental factors in genetic predispositions and little is
known about developmental abnormalities or epigenetic
dysregulation that might predisposed individuals to develop
pulmonary hypertension or COPD in adults. So these authors screen
a cohort of human pulmonary hypertension in COPD patients for
changes of histone modifications by immunofluorescent staining.
And also, they developed knockout mouse lines targeting
cardiopulmonary progenitor cells and different heart and lung
cell types.


Dr. Greg Hundley:


Now molecular, cellular and biochemical techniques were applied
to analyze the function of SUV420H1-dependent epigenetic
processes in cardiopulmonary progenitor cells and their
derivatives. Well, what did they find? So the investigators found
that loss of SUV420H1 in cardiopulmonary progenitor cells caused
a COPD-like pulmonary hypertension phenotype in mice, including
formation of perivascular tertiary lymphoid tissue, and goblet
cell hyperplasia, hyperproliferation of smooth muscle cells and
myofibroblast, impaired alveolarization and maturation of defects
of the microvasculature leading to massive ripe ventricular
dilation and premature death.


Dr. Greg Hundley:


Now mechanistically SUV420H1 bound directly to the five prime
upstream in regulatory element of Superoxide Dismutase 3 gene to
repress its expression and increased levels of the extracellular
Superoxide Dismutase 3 enzyme in SUV420H1 mutants increased
hydrogen peroxide concentration causing vascular defects and
impairing alveolarization. So what can we take away, listeners,
from this clinically? Well, the author's findings reveal a
pivotal role of histone modifier SUV420H1 in cardiopulmonary
co-development and uncover developmental origins of
cardiopulmonary diseases. And now these results suggest that this
study will facilitate the understanding of pathogenic events
causing pulmonary hypertension in COPD and aid the development of
epigenetic drugs for treatment of other cardiopulmonary diseases.


Dr. Greg Hundley:


Well, listeners, what else is in, we call it, the mail bag, but
some of the other articles in the issue? Well, doctors Varricchi
and Wang exchanged letters regarding the prior article, the role
of IgE FcεRI in pathological cardiac remodeling and dysfunction.
And our own Sara O'Brien highlights articles from our circulation
family of journals. Professor Ross has a Research Letter
regarding the effects of walnut consumption for two years on
lipoprotein subclasses among healthy elders findings from the
WAHA randomized controlled trial. And then finally, Dr. Maurer
has a really nice On My Mind piece that raises concerns
pertaining to the use of cardiac scintigraphy and screening for
transthyretin cardiac amyloidosis. And now listeners, we're going
to turn to that forum discussion where we have an author, our
associate editors and an editorialist discussing two really
important papers from the ischemia trial.


Dr. Greg Hundley:


Well, listeners, we are very excited today to discuss in sort of
the forum feature, two papers pertaining to the ischemia trial.
And with us this day, we have Dr. Harmony Reynolds from New York
University Grossman School of Medicine in New York city; two of
our associate editors, Dr. Nick Mills from university of
Edinburgh in Scotland; and Dr. Sandeep Das from UT Southwestern;
and then also an editorialist, Dr. David Newby, who's also
University of Edinburgh in Scotland. Welcome to everyone.


Dr. Greg Hundley:


Harmony, we're going to start with you. And in the first paper,
the natural history of ischemia and no obstructive coronary
artery disease, can you describe for us a little bit of the
context of what shaped this question for you, what hypothesis did
you want to test? And then describe for us a little bit your
study population and your study design.


Dr. Harmony Reynolds:


Sure. Thanks so much for having me here to discuss these papers.
I'm really appreciative of the attention from circulation, and
I'm excited for this discussion today. So in this first natural
history paper, we were looking at ischemia with non-obstructive
corona arteries, INOCA, the kind of thing that used to be called
cardiac syndrome X. And we know this is an extremely common
problem. It's defined by having signs or symptoms of ischemia and
no 50% or greater lesion on coronary imaging. And we also know
from prior invasive studies that the mechanisms of this are
overwhelmingly microvascular coronary disease and provokable
coronary spasm. Some patients prove to be normal and invasive
testing, but most will have some objective abnormality.


Dr. Harmony Reynolds:


We know this problem is associated with a higher risk of
cardiovascular events and with high costs, but what we didn't
know was whether the symptoms and ischemia on stress testing are
tracking together in these patients. So if we're trying to treat
these patients, should we be doing serial stress testing and
targeting the medical therapy to ischemia abrogation or should we
just be making their symptoms go away? And would this provide any
long range insights for us into when we can figure out the
symptom are truly ischemic in nature?


Dr. Harmony Reynolds:


So we decided to use the ischemia trial, and we had a fantastic
platform for that in ischemia because, as you know, patients were
screened in part for randomization using coronary CT angiography.
And even though these patients had moderate or severe ischemia,
some had no obstructive coronary disease on that CT coronary
angiogram. And those are the patients that we enrolled in
CIAO-ISCHEMIA. They had an assessment of angina at baseline, and
they had to be symptomatic at some point. They didn't have to be
symptomatic at the moment. They were enrolled in CIAO, but they
had their stress test generally to evaluate ischemic symptoms.
And they had their stress echocardiogram read by a core lab.
Importantly, that core lab did not know the result of that CT
scan. So they read them like all the other ischemia stress
echoes. And then these patients had an angina and ischemia
assessment with a repeat stress echo at one year.


Dr. Greg Hundley:


And what did you find?


Dr. Harmony Reynolds:


There were a number of interesting findings from this study. The
first thing was that the severity of ischemia in the CIAO
patients with INOCA was very similar to the ischemia patients who
had obstructive coronary disease. So that tells us that the INOCA
problem can happen with quite a lot of ischemia, and that had not
been as well delineated before. Another finding expected, but we
did find that is that there were many more women in the INOCA
group, two thirds of our child population was female. And in
ischemia, overall, it was closer to a quarter. We found that the
symptoms and the ischemia were quite changeable. So at one year,
the stress echocardiogram was normal in half of the child
participant and only 23% still had moderate or severe ischemia.
Angina had improved in 43%, and it worsened in 14%. There was an
awful lot of change over one year, but the change in angina and
the change in ischemia did not track together. And that was a bit
of a surprise to me.


Dr. Greg Hundley:


Very nice. Well, Nick, I know serving it as an associate editor,
you see many papers come across your desk. What attracted you to
pushing this paper forward for publication?


Dr. Nicholas Mills:


Thanks, Greg, and congratulations. Harmony, we love the papers
you've been sending from ischemia trial, which genuinely is
changing clinical practice all over the world. And it's been
great to see the secondary analysis and follow-up papers. So this
paper attracted me because it addresses an area where I still
don't fully understand in clinical practice, what recommendations
to make for my patients and what tests to arrange. As you say,
INOCA is more common in women. I think these patients have
largely been understudied over many decades, and there remains a
lot of uncertainty. I liked it because you had a core lab,
blinded core lab analysis with systematic follow up and it was a
really well-done study. It reassured me in many ways because it
told me that actually a lot of these patients, their symptoms get
better, sort of irrespective of what we do. The treatments didn't
seem to track within improvements of symptom, nor did the
severity of ischemia, and that I think provides a lot of
reassurance to our patients who are in this situation.


Dr. Nicholas Mills:


Of course, there is a group there who continue to have moderate
to severe ischemia a year later. And I think this trial helps us
understand maybe how we should study this group more, understand
the heterogeneity that you've observed in this population in
order to really try and resolve that and resolve their ongoing
symptoms. But for the majority, four in five patients, they're
going to do well and they're going to get better over time. And I
think that's an important message from this study.


Dr. Greg Hundley:


Thank you so much, Nick. Well, Harmony, we're going to come back
to you. You have a second paper, the outcomes in the ischemia
trial really based on coronary artery disease and ischemia
severity. Can you describe for us, again, working us back
through, what were some of the constructs that you really wanted
to address here? What was your hypothesis? And again, how did
this study population maybe differ a little bit in this second
paper?


Dr. Harmony Reynolds:


Thanks so much. So this paper tracked outcomes based on the
severity of ischemia and the severity of coronary artery disease
on the CT coronary angiogram now in randomized patients in the
ischemia trial. So all of these had obstructive coronary disease
and they were selected for randomization. And the premise of the
ischemia trial was partly that we would be able to select
patients who might benefit from revascularization and from an
invasive strategy really based on how much ischemia they had on
the stress test. Moderate or severe ischemia was required for
randomization and for entry into the trial, but a core lab read
those stress tests independently and independently assessed
ischemia. And in some cases, when the site thought there was
moderate or severe ischemia, the core lab did not agree. And the
core lab independently decided whether it was moderate or severe.
So we wanted to understand whether the ischemia severity at the
time of trial entry influenced outcomes and influenced the
outcomes by randomization treatment assignment.


Dr. Harmony Reynolds:


Similarly, about half of the patient had a CT that was
interpretable for the number of vessels disease. And we wanted to
understand in the context of all those prior stable ischemic
heart disease trials, showing a lot of heterogeneity by the
amount of coronary disease, whether in ischemia as well, there
would be heterogeneity of the treatment effect based on how much
coronary disease you started with. So the ischemia population,
and this is almost the entire randomized cohort, but it's
important to recognize for the CT analysis that only about three
quarters of the patients had CT. They didn't get a CT, if your
GFR was too low or if you had known coronary anatomy. And among
those Cts, not every CT is perfectly interpretable for the number
of vessels disease. These are sicker patients. These are not the
super stable patients who have a low prevalence of disease. These
were pretty sick, multi-vessel coronary disease patients, and
they couldn't always hold their breast all that well. There was a
lot of calcification in these.


Dr. Harmony Reynolds:


So for example, if there was motion artifact in the right
coronary artery, we wouldn't be able to quantify the number of
vessels disease. And that left us with a cohort of about half of
our ischemia population, but that's still a giant cohort of
several thousand patients. So that's how our study.


Dr. Greg Hundley:


Very good. And what did you find here?


Dr. Harmony Reynolds:


Here, we found that more severe ischemia was not associated with
outcomes. Now that does go along with the COURAGE study in which
after you adjust for clinical characteristics, ischemia was not
associated with outcomes. But still it came as something of a
surprise that even severe ischemia was not associated with a
higher risk of outcomes than moderate or mild ischemia. We also
found that in the coronary disease group, no matter how you
measure the severity of coronary disease, the Duke prognostic
index, the number of vessels disease, the segment involvement
score, the segment stenosis score, all of these measures were
very strongly associated with our outcomes, whether it was all
cause mortality MI or our composite.


Dr. Harmony Reynolds:


When it came to treatment effect, we found that the ischemia
severity were no relationship to treatment effect. There was no
ischemia subgroup in which there appeared to be an advantage with
an invasive strategy. But in the coronary disease group, and
again taking into account the caveats of not everybody had a CT
interpretable for the number of vessels disease, in those with
the most severe coronary disease, that's the Duke 6 subgroup. And
they had multi-vessel severe disease, either two vessel including
the proximal LAD at 70% or three vessels with 70% stenosis. There
was no benefit on mortality. But if we looked at the composite
endpoint of cardiovascular death or MI, there appeared to be some
advantage to the invasive strategy.


Dr. Greg Hundley:


Very good. Well, Sandeep, similar to Nick, working as an
associate editor and meeting weekly, what attracted you to this
particular paper? And why did you want to really see it come
forward to be published?


Dr. Sandeep Das:


So first of all, I want to echo Nick's comments that these are
great papers, and thanks very much for sending those our way and
letting us have sort of first crack at them before they're
released to the world. And I also want to comment on the side
that Harmony and her team were just absolutely fantastic to work
with in this process. From having been on the other side when you
get 300 different comments from the editors and reviewers and you
respond to them thoroughly and with grace, that's a feat in and
of itself. So I want to shout out Harmony and her team for just
being fantastic partners, because really we see ourselves as sort
of the author's partners in kind of making the paper as good as
it can be as the best it can be.


Dr. Sandeep Das:


So I'll admit upfront, I think it's kind of fashionable for
people to say, well, I knew that this was going to show this, I
knew this all from COURAGE, and this is not surprising to me. But
I'll admit that I was surprised. And so this has been
practice-changing for me, so this whole evolution post ischemia.
And I really feel like a little bit of an existential crisis
because I'm not sure I understand what ischemia means anymore.
You ask me five years ago, I would've been very confident that I
knew the answer to that. So you know what, really, as soon as
this paper crossed our desk, I thought, wow, this is something we
want to keep, this is something that's going to be really
important to practice of cardiology. It's going to be really
important to our readers. It's a great paper from a great group.
This is something we want. So really it was never a question of,
well, am I interested or am I not? I was interested from reading
the abstract.


Dr. Sandeep Das:


So the question then became what are the real important questions
that we need to sort of tease out and help elucidate for the
clinician for the reader? And really for me, the question has
always been, is there a subset of people where... So in my heart
of hearts, I always kind of thought that burden of ischemia, if
there was enough burden of ischemia, that it probably did help to
revascularize that, right? I definitely practiced that way,
right? There was some sort of number where I would start to say,
that's a lot of ischemic myocardium and maybe we need to do
something about that. Even though I know my intellectual brain
says, no, there's no data that supports this, I really kind of
thought it was true. And so Harmony and her team put another nail
in that coffin here because it doesn't seem to be true, which to
me was interesting and different and practice-changing.


Dr. Sandeep Das:


So the real questions here were sort of to tease out the
interaction between anatomic severity, and we've all known that
sort of anatomic burden of disease is proportional to adverse
outcomes. That's not surprising. But the question then is, can we
tease out a group where there may be benefit to
revascularization? So there's a real interesting sort of
interplay here between degree of ischemia and anatomic burden of
disease. And is there a subset with enough of an anatomic burden
of disease where you really may be interested in going after that
to improve heart outcomes? So that's what I thought this was
really fascinating paper.


Dr. Greg Hundley:


Very good. Well, David, we're going to turn to you next as the
editorialist and asking you to sort of put the results of each of
these two studies together. One, kind of highlighting for us how
functional imaging might be useful to identify whether ischemia
is present or not. And then the second study, really defining for
us an association between anatomy and outcomes. So putting these
all together, could you share your thoughts with us regarding
these two papers?


Dr. David Newby:


Yes. Thank you. So I think that the CIAO-ISCHEMIA is very
interesting, isn't it? And those clinicians were often challenged
with symptoms versus our objective tests and trying to work out
exactly what's going on, and it is. And such an important group
as Harmony says, I can't agree more. We have a lot of morbidity
here. As Nick said, I think the short term, a lot of the patients
do seem to get better with just conservative management is good,
but there's a core group that clearly are a problem. And as
Harmony highlighted, you've got people with terrible regional
wall-motion abnormalities on stress echo and yet no angina,
others with no angina with no apparent difficulty on repeat
testing. And then you've got a core group that has both, and it
is fascinating to try and unpick that. And clearly, the symptoms
are not correlating with our tests, and that's not the patient's
fault.


Dr. David Newby:


And very often, no, no, you're wrong, can we say that to the
patient? No, no, the patient is right and our tests are wrong,
and we've got to work out how best to manage them. And I have a
bit of analogy with Takotsubo cardiomyopathy as well, I think is
at play here. I mean, here, you've got people with stable pain.
We're not coming in as an acute emergency, but they're having
regional wall motion abnormalities at times. They're getting a
lot of symptoms. And we see similar things with Takotsubo, which
is, I suppose, a much more flurry thing. I know that's something
close to Harmony's his heart too. Excuse the pun. But this
ischemia relationship, these regional wall motion abnormalities
with chest pain, particularly in women, is something we really
need to get our heads around and understand what's going on. It
just reflects our ignorance, I think, of knowing exactly how to
manage these patients.


Dr. David Newby:


And so for me, ischemia testing is about symptoms. It's about
working out what's going on with the patient. It doesn't always
give us the answer, but I certainly think that the role of
ischemia testing is more about the symptoms.


Dr. David Newby:


And then when it comes to the second paper and outcomes with the
ischemia trial, I absolutely was delighted to see those findings.
I have to say place to what my prejudice is, I suppose, as
someone that's been working with CT. And I suppose the slightly
obvious thing is that the more disease you have, the more you
will benefit from an intervention. And plaque and the burden of
plaque is critical to that because how do you have a heart
attack? Well, you have to have plaque, right? And it has to
rupture. So the more plaque you have, the more likely you are.
And I think that the analysis is again reinforcing what we've
learned from some of the imaging trials with PROMIS and
SCOT-HEART. Actually, the more plaque you have, the worse you
are.


Dr. David Newby:


And yes, ischemia predicts risk, but ischemia predicts risk
through its association with plaque burden, not through ischemia
itself. And what I think we're seeing very nicely being played
out in ischemia trial is the risk is definitely much stronger for
CT than it is for imaging. And that's very clear, and that's
exactly what PROMIS found exactly what SCOT-HEART found as well,
and it's a rise robust finding. The interaction with the
treatment effect that I find also fascinating and again plays to
some of the bypass surgery trials that we've seen, bypass surgery
tends to prevent spontaneous MIs and, even in some cases,
mortality. And we're seeing trends in ischemia for mortality,
can't over call them. I'd love to see what happens in 10 years.
But I think in terms of the prevention of MIs, I'm putting all my
money in one basket, which is the bypass surgery, 25% of course
of patients revascularized that way. I don't believe that PCI is
going to prevent the myocardial infarction. So I think all my
money is in that box.


Dr. David Newby:


But it's absolutely fascinating data. It is all about the plaque
if you're talking about prevention of clinical events downstream.
And I think that's where the dichotomy is, scheme is about
symptoms and understanding the patient's problems in terms of
symptomatic improvement. If you want to improve their long term
outcome, it's all about the plaque, understanding the burden of
plaque and what you can do to hopefully prevent downstream event.


Dr. Greg Hundley:


Great. Thank you so much. And so listeners, we're going to ask
each of our speakers today in really 20 or 30 seconds to go
through and identify what do they think is the next study really
to be performed in this space? So Harmony, we're going to start
with you and then Nick, Sandeep and then finish up with David.
Harmony?


Dr. Harmony Reynolds:


Thanks. Well, when it comes to INOCA, I would like to see more
studies in the vein of CorMicA. So I'd like to see routine
invasive testing to define the underlying pathophysiology problem
and then targeted medical therapy interventions, and I'd like to
see outcome trials. There's one outcome trial going on. It's a
challenge because the event rate, though very important and
higher than in the general population for sure, is low enough
that these trials have to be quite large, and we look at ischemia
with a relatively high event rate. And even so it's a stable
population and that had to be large, this would have to be even
larger. So we're going to need more mechanistic studies in order
to lead to the treatment trials that will really influence
practice.


Dr. Harmony Reynolds:


And in terms of the severity of coronary disease, this is a tough
one. We felt like ischemia was a lift, and I'm not sure that
there will be another huge stable ischemic heart disease trial.
But sure, I'd love to see in people selected by CT for their
advanced severity of coronary disease, whether an invasive
management strategy makes a difference compared to medical
therapy. I don't know that we'll see that one come to pass, but
you never know.


Dr. Greg Hundley:


Nick?


Dr. Nicholas Mills:


Yeah. I agree. We need more mechanistic research, but I'd like to
see more non-invasive methods to understand the mechanistic basis
of this condition because CorMicA has caught an invasive protocol
for a condition, which we know is benign and who most patients
get better without any treatment. I would also like to see
randomized blinded studies of treatment effects and because there
are too many observational on blinded studies here. And I think
the outcome has to be patient-focused and symptoms.


Dr. Greg Hundley:


Sandeep?


Dr. Sandeep Das:


Yeah. So everything that's been raised so far are fantastic
comments and really on point. For me, I think if we can tease out
the population that may benefit to get back to Dave's earlier
comment that there's possibly not going to be a little humble
here, there's possibly a population that has extensive, extensive
CVD that could benefit from bypass surgery. And I think that that
hasn't really been firmly demonstrated yet, although it's been
suggested strongly. So that I think is an interesting study, and
I hope that that gets done as a trial, but I can understand that
it'd be a giant undertaking. And then the other thing I think is
just algorithmic approaches that are driven by anatomical studies
like SCOT-HEART and things like that, where we really try to make
decisions based on the anatomical approach and pretend like the
last 15 years never happened and that we kind are starting fresh
with our best approach to how to treat these patients.


Dr. Greg Hundley:


And finally, David.


Dr. David Newby:


Yeah. I'm actually going to agree with everybody there, and I'm
rooting for this trial actually because that's the one I want to
do is look at advanced coronary disease on noninvasive imaging,
irrespective of symptoms. And that's the big call actually if
you've got no symptoms to put yourself through a bypass, because
it's bypass, it's not standing. Bypass, we need. I'd also love to
see some substudy coming out of ischemia. I think you're doing
them. I hope you are looking at plaque burden and plaque
characteristics because I think that's another level of
complexity. We're so obsessed with stenosis, actually. And again,
even anatomical and ischemia testing plays to that, it's not just
about stenosis, stenotic arteries have big plaque burdens, et
cetera. And it's not bypassing them, it's bypassing all the
nonobstructive plaque and the obstructive plaque that has given
you the benefit of revascularization with surgery. So I think you
need to think about a really nice cool trial where we can do that
trial even in the presence of nonobstructive disease, but big
plaque burden, adverse plaque characteristics, and think about
bypass.


Dr. Greg Hundley:


Very nice. Well, listeners, we want to thank Dr. Harmony Reynolds
for bringing us these two really informative studies from the
ischemia trial, and also our associate editors, Dr. Nick Mills
and Dr. Sandeep Das for providing their perspective and our
editorialist, Dr. David Newby, who really helped us organize our
thoughts and put both of these two studies into great perspective
highlighting in the first that functional testing can really help
us identify the presence or absence of ischemia. And then our
second study highlighting the association between CT coronary
angiography and the identification of the anatomic severity of
disease with cardiac outcomes.


Dr. Greg Hundley:


Well, on behalf of Carolyn and myself, we want to wish you a
great week and we will catch you next week on the run. This
program is copyright of the American Heart Association 2021. The
opinions expressed by speaker in this podcast are their own and
not necessarily those of the editors or of the American Heart
Association. For more, visit ahajournals.org.