Circulation October 06, 2020 Issue

Dr James de Lemos: Hello, my name is James de Lemos. I'm the
executive editor for Circulation, and I'm delighted to be joined
here by Tim Gardner professor of surgery at University of
Pennsylvania and our long-term associate editor in charge of
cardiac surgical content at Circulation; and Marc Ruel, who is
professor of cardiac surgery at University of Ottawa and the
chair of the department there and who for many years has led the
cardiac surgery supplement issue. Mark, Tim, welcome. Marc,
please introduce this issue for our listeners.



Dr Marc Ruel: Thanks so much, James. It's a very exciting year
academically for cardiac surgery. We've had a lot of great
developments from new data on long-term patency and outcomes with
radial artery graphs through the results of the ischemia trial.
And I think the 2020 themed issue around cardiovascular surgery
is exactly in that framework. I think it will garner wide
interest.
It has a number of original papers, six original research
articles, two more translational papers included in those six. We
have two research letters. We have two frame of reference papers
as well. And one state-of-the-art piece on exynos
transplantation. We always keep in mind to have those issues very
relevant to surgeons and to gather the very best cardiovascular
surgery science. But in the same token we also want to make sure
that they are relevant to the wider cardiovascular community. So
I think, and I hope that everyone will enjoy this issue as the
very best that's happened in cardiovascular surgery over the
year.



Dr James de Lemos: Well, thank you, Mark. Let's get started with
discussion of the first paper and one that I'm actually quite
excited about. This is long-term results of the radial artery
CABG in clinical outcomes trials. What did the investigators look
at in the study?



Dr Marc Ruel: I think this is a very important paper, which adds
to the increasing data around long-term benefits of arterial
grafts, multi arterial grafts, and more specifically the radial
artery. So here's a paper mostly from Australia. First author
being Professor Buxton, who is a very well-known senior surgeon
who has been really a grandfather in this field. And the last
author is David Hare who is a cardiologist, also professor in
Australia.
And essentially there were two radial artery comparative trials
that have been undertaken many years ago, well over a decade ago,
when we now have 10-year data on those two trials. One of the
trials compared the radial artery to the right internal thoracic
artery. And the second trial a little bit smaller to the
saphenous is vein grafts. So it holds 400 patients in the first
randomized comparison and around 225 in the second, i.e. the
radial versus saphenous vein.
So it's wonderful that this is very long-term data. We have 10
year patency data, not on all patients. There was a distribution
as to when the angiogram or the CT scan would be performed for
patency over the course of the 10 years of the study. But the
follow up is excellent and there are actually patency as well as
clinical differences between the groups.
And maybe I can say a couple of things around those. So, in the
radial versus right internal thoracic artery cohort, there's both
a patency and a mortality as well as a major adverse cardiac
events benefit for the radial artery over the right internal
thoracic artery. And yes, you've heard right, the comparator is
the right internal thoracic artery.
Now a couple of chatty it's all the Redis in there had to be done
as a free graph. So they are connected. This is an art technique
that everyone is very comfortable with and you have to use a six
or seven Oh one friable internal thoracic ultra.
So it may not really provide or present the call the way at its
best advantage. If you will, there may be some benefits or a loss
for not having it as a pedicle, but nevertheless, and in the
second comparison, looking at the radio versus 225 patients,
there was a patiency advantage for the radio Herceptin in
Spain.
But partly because the comparison was less power than the first,
there was no major adverse cardiac event or even mortality
difference. So I think again, aligns with the data that we know
the arc trial, as we all know, 10 years was neutral. There was no
benefit to internal thoracic arteries versus small one, which
regards to anything repeat revascularization based
mortality.
And we know have 10-year data recently published that shows that
the radial artery in pooling patient level data from many
randomized clinical trials leased their survival benefits. So I
think it's fair to say based on available data now with this team
issue in 2020 in the fall, that the best second RGO is very
likely or radio RV and too many people surprised.



Dr Timothy Gardner: Yeah. If I could just add my perspective,
there's an editorial by Steve brings on this. This really does
solidify the data about long-term radial, artery patency. And
that was when I came away with, it's not so much the comparison
of the radial on the right internal thoracic, but the fact that
the radial artery would be like held up very well.



Dr James de Lemos: If you're referring a young patient or
considering a young non-diabetic patient for cabbage at this
point, was you select a radial artery or right internal memory?



Dr Timothy Gardner: Well, I probably would favorite as a second
graph the right internal thoracic artery rather than. As a free
graph, but I certainly wouldn't hesitate to use the radial artery
as the second graph there as a third grade. My competence in the
radial artery continues to grow in this report reinforces that.



Dr James de Lemos: Excellent really important study for both the
cardiac surgeons and the cardiologists that read our
journal.
Let's switch gears and talk about bowel surgery, Tim, the camera
Cardiolite study drills deep into different strategies for
repairing the mitral valve. What did we learn there?


Dr Timothy Gardner: Well, first of all, this study, which comes
from Mark Raul's unit Benson Chan being the first author and
address the issue that repair with resection of the mitral valve
made me to functional stenosis of the valve. And that has been a
concern among surgeons and that has led some surgeons to prefer
non-lethal the resections repair. And this study was very
carefully done and actually demonstrated that the data did not
support the fact that resection versus preservation is this okay
with the riff? So I think that, you know, there are various ways
to repair the valve. And if you go back to the original
descriptions of mitral valve repair resection was a major
component for many people in many studies. And this is a
reassuring study that either approach appears to be effective
without badly under sizing the annulus that there should not be
residual mitral stenosis.



Dr James de Lemos: Tim is one of these materially easier to do in
the operating room. So then it would emerge as the preferred
therapy or is it really going to be surgeon dependent.



Dr Timothy Gardner: I think it’s fairly surgeons dependent. I
mean, we have technical variations for a lot of operations, and I
think it's when the surgeon is comfortable with Mark. You might
want to comment on that point.



Dr Marc Ruel: Yeah, I agree with both of you. I think it's very
reassuring because there's the orientation of where the last
issue is. Small. The patient's exposure is not knowing that you
can use theater technique and in some cases not have to go on to
the pathway. We Muscle is a reassuring avenue. So I think every
surgeon has her or his preference, but it's nice to know that
both these can be used interchangeably without any drawback to
the patient.



Dr Timothy Gardner: Let's switch gears and talk about a paper
that I think has pretty profound implications for both of our
specialties. And this is an observational analysis from the RS
trial, evaluating the association of postoperative atrial
fibrillation in the long-term risk of stroke. Mark, what did you
think of this paper and its implications?



Dr Marc Ruel: This is a very interesting piece that comes
incidentally from the heart trials. So non related to what we
were
Just discussing before the 3000 patients or so of the art trial
were followed at 10 years. Mostly with regards to major adverse
cardiac events, et cetera, anything that's related to the
question at stake at the time, which was single internal for us,
incidentally, the authors have ready data regarding the incidence
of stroke at 10 years. And they were able to use those and go
back to those stations who have postoperative atrial fibrillation
and see if there was a correlation, even when accounting for
other factors in the patient profile. So interestingly about 24%
of patients have had post-op and post-op you, is defined in
variety of ways for this particular study, it was defined as 30
seconds at least of atrial fibrillation or atrial flutter during
the index hospitalization after the operation. So I think this is
a very fair and square type of definition and those patients and
those who have the CBA incidents by 10 years was 6.3% versus
those who did not have postoperative 3.7%.
So this is obviously a significant numerical and also
statistically significant higher risk for those patients who have
post-operative a-fib. So there's a number of caveats around that.
All the risks for post-doc are often the same ones that may lead
to the risk of stroke over the long-term. So I think we should
see this not as probation. But that should be not even as an
association. But certainly as a correlation, but it is really
unique data that has not been produced before. Like postoperative
is so common after cardiac surgery. It affects many of the
patients that both the cardiology and cardiac surgery individuals
have to treat.
And I think the more information on it, the better, there were a
number of interesting observations warfarin, for instance, even
though the incidence of post-op 24% was used in only about 8% of
the overall trial. So one may debate, have these patients being
anticoagulated enough also, would there be a way to provide
enhanced surveillance to patients who have post-op in order to
maybe catch them prior to them having a cerebral aspir
event?
So I think it's really very interesting data. I would like to
briefly provide one last tidbit of information, which I thought
was very, very fasting. So the authors used the CHADS two score
in order to kind of ascertain your overall risk attributed to
which regards to stroke in those patients. So this is probably
the latest and best iteration of the Chad score if you
will.
And they found that in patients with a score of less than four,
so it was zero to three. There was no difference with regards to
the incidents of CVA or in signers versus those who have post-op
after the operation. However, when the score rich four or higher.
This is rare to you where the risk was concentrated. So that
particular cohort of patients seemed to be the one where I think
the efforts with subsequent studies should be concentrated in
order to intervene and hopefully catch these patients who may
have atrial fibrillation without having it.



Dr James de Lemos: Does this change your practice at all? Do you
think, I mean, I guess it's interesting for me because obviously
I see a lot of these patients back from surgery and I've tended
to candidly ignore short episodes of peri-operative atrial
fibrillation. And this really raises questions as to whether that
approach is wise and needs to be revisited.



Dr Timothy Gardner: I agree completely on the other hand, I think
that targeting patients, I mean, I think the last point that Mark
made about the patients that ended up with problems with higher
AFib and with consequences had other risk factors associated with
their risk of stroke. So this continues to be a really tough
group to manage. I think that one question that we all have is do
the, the, the new novel oral anticoagulant agents provide better
long-term protection. As a topic for another important study that
should be coming down the pipe pretty soon.



Dr James de Lemos: And I'll just point out to our listeners that
at the American heart association meeting in November, that late
breaking trial will be presented called search AI cardio length
that will evaluate extended monitoring creature fibrillation
after surgery. And I think that will build off, of this theme
that perhaps atrial fibrillation after cardiac surgery is a more
important tissue than many of us considered.
Let's move to the next paper, Tim, this is really right in your
wheelhouse in terms of surgical. So specialization. And this is
an interesting paper. I thought evaluating variation and
congenital heart surgery outcomes across centers in the U.S. and
this group really evaluated a large proportion of dissenters
doing congenital heart surgery in the U S.



Dr Timothy Gardner: Yeah, absolutely. And they made use of the
STS database. They've got good data and it is a
multi-institutional review group, really looking at how to
optimize outcomes. And I think that, the assumption is that
regionalization with more attention to high volume centers,
especially for the most high risk say neonatal heart surgery is
the way to go.
But this study actually while demonstrating significant hospital
variations also demonstrated that and reading their conclusion.
Now a substantial portion of potential improvements that could be
realized on a national scale are related to variability among
lower risk patients. And this makes me think back to Dr John
Kirkland, who was maybe the first one in our field to actually
develop a checklist of important steps and management strategies
during the surgical procedure in the early post-operative
period.
He worked with IBM on that. And I think that lesson here that I
take away from it is that volume may be important, but not just
for the high risk neonatal population, but for all congenital
heart surgery patients. And it really is an important specialty.
And there may be some opportunities for improvement just by
standardizing sort of management of even the lower risk patients.
This is one of several reports from this multi-institutional
group that is focused on data from the STS database in congenital
heart surgery. Good job demonstrating these variations in
outcome.



Dr James de Lemos: Yeah. And I think tremendously important,
right? Because these lower risk in general procedures may be more
like other procedures that cardiac surgeons do. And I think you
make a great point that these systems based approaches to
minimizing variation do seem to matter. And I wouldn't have
thought that the, this is another one of the theme really here in
the issue where we have a lot of studies that are challenging the
way we thought about, common medical and surgical problems,
really a fascinating piece.
Let me take a moment here to introduce a new member of our team
for the themed issue. Mike Fischbein, who's a surgeon scientist
at Stanford, a practicing cardiac surgeon on the faculty there,
but also runs a large and very successful basic science
laboratory. And he has joined the surgical team for the themed
issue to add his particular expertise in the evaluation of the
basic science papers.
Mike, welcome to the team. I think our readers and listeners will
really benefit from having your perspective. And I'd like to have
you now please talk about the basic science papers here in the
issue.



Dr Michael Fischbein: Thank you very much, James. It's really a
pleasure to be part of a team. The paper that I'd like to discuss
today is a feature of basic science paper entitled a Single cell
Transcriptome Analysis Reveals Dynamic Cell Populations and
Differential Gene Expression Patterns and Control and Aneurysm
Human Aortic Tissue. This is from Scott LeMarie group from the
Department of Surgery at Baylor College of Medicine. I think this
study is very important. It's focusing on the ascending, thoracic
aortic aneurysm, as you know, ACE and aortic aneurysms are the
second most common aneurysm after abdominal aortic aneurysms. One
of the risk factors of ascending aortic aneurysms is that as they
grow, they can tear dissect or rupture.
Both of which are life-threatening currently the only treatment
option is prophylactic surgery. And this is really based on size
criteria alone. Now, while over time, we've established that
smooth muscle cell loss and exhale and matrix breakdown are
important during this process, really the molecular mechanisms or
pathophysiology is poorly understood. Therefore, limiting
development is novel drug regimen, and this manuscript, the
authors use single RNA sequencing to compare the aneurysm wall to
normal control. Aorta is taken from transplant recipients. One of
the benefits of single cell RNA sequencing is that allows one to
identify the cellular components or heterogeneity within the
aortic wall. And it also allows us to see the aneurysm relevant
transcriptome changes in the major vascular cell types within the
aorta. The authors identified 11 major cell types in the aorta,
including a number of different smooth muscle cell subtypes and
to Celia's cells, fibroblasts and inflammatory cells, including
T-cells and macrophages.
They found over 500 altered genes comparing the aortic wall to
normal control. Mitochondrial dysfunction seemed to be altered in
several gene types and they identified a transcripted factor ERG,
which stands for Erythroblast Transformative, specific Related
Genes to be important in maintaining the normal aortic wall
function. And this was reduced specifically in smooth muscle
cells, fibroblasts and endothelial cells. This is really an
exciting target that may lead to drug development in the future.
So thank you very much, James, for allowing me to participate in
the group. And I think this will be an exciting paper for the
readers.



Dr James de Lemos: So Mike, thanks so much. Really appreciate
your perspectives here. Another really interesting area that is
quite forward-thinking Mark is this idea of 3D printing. Theotic
roots and conduits. Tell us about this paper from Joe Woo’s
group.



Dr Marc Ruel: This is another great contribution from Joe's lab.
Looking at the issue around bell spring, and many would call it
bear hair because essentially they preserve and surgeons go to
great pain and great strides to try to recreate if you will be
normal slash nets, these geology and aortic root sinuses. And
many of us, when we do this operation are taking great minutia
and creating those. And there's a number of things that happen.
And all of these techniques vary from the more approach of just
taking a straight to, and essentially reinventing the native
aortic valve and connecting the coronary buttons. So Joe's lab
wanted to study this with regards to the translationally relevant
outcome of opening velocity and closing gossip with regards to
the RP pal.
And they've done this 3D printed biomechanical study, aware they
have used for signing LT. Val, that'd be put into these different
configurations, some including Neil, if you will, some including
what we call a bell solver type of breath and using the natives
or signing as a control in the same 3d biomechanical model. And
essentially the conclusions of the study, which is free, elegant
be performed and Bree compelling from a data point of view is
that a simpler appears to be better too many.
I'm sure the investigators I'm sure what will be many readers
price. These trade routes' configuration without Neil sinuses
seem to have the lowest coast opening and closing velocity. So it
would suggest that this may translate into longer term durability
of the valve. Now, there are other reasons why someone, for
instance, the one I do this operation, I like to use Valsalva
graft. It's not because I so strongly believe that Neo sinus type
should be there is because it also gives enhance an easier reach
to the corny about adding a vertical followed by a horizontal
type of pattern I find is a bit more reliable and it may not
really matter what the opening and closing philosophies are
because those files are not intrinsically abnormal.
So they may last for many decades going forward. But
nevertheless, I think this is a very important study and series
of experiments, and we're very happy to include it in the theme
this year.



Dr Timothy Gardner: Yeah. And if I could just add the thing that
I admire most about this study is that not just how they come up
with this innovative, 3D printing way to model, but the team
included mechanical engineers and bioengineers at Stanford, and
that's adding real substantial science to what some surgeons have
theorized about. So this is a small study, but the results are
quite interesting. Let's talk now.



Dr James de Lemos: It's about this remarkable Primer that we've
had on critics, transplantation. This is something I wouldn't
have imagined five years ago would be something we'd have even
considered close enough to clinical application to publish in
circulation. But what's different about this now and what should
our readers look to in the future with this technique.



Dr Timothy Gardner: This paper comes from a group at the Mass
General [Hospital]. They've continued to work on
Xenotransplantation as a possible solution to the need for new
donor organs. And I think the most remarkable thing is after
almost silence for 10 years, they have outlined the possibility
much more realistically now of coming up with Xenotransplantation
as a usable alternative, based on some very important basic
science work that others have done in baboons and that they have
model into additional experiments. This is what was a very
informative article for me. And it's still some ground to cover,
but they've really worked away at the science and think that they
believe that they're nearing the point where they know
transplantation or for cardiac replacement is a possibility.
Again, amazed I sort of thought Xenotransplantation was an
impossible dream 10 years ago. And here we are, perhaps at the
point where it is more of a realistic possibility.



Dr James de Lemos: Really remarkable. When you think about these
technologic advances that are getting so much closer to clinical
application. Well.



Dr Timothy Gardner: Thank you both. I'd like to take just a
moment to recognize Sara O'Brien in [the] Circulation Editorial
Offices in Boston for her remarkable contributions yet again, to
pulling this issue together and keeping Mark and Tim and Mike and
myself on task to bring this issue home. And thank Mark Tim and
Mike for pulling together. What I really believe is far and away,
our finest issue. We're talking here in my opinion about multiple
studies that changed the way we think about cardiovascular
surgery and its complications, including atrial fibrillation that
affects all of us in cardiovascular medicine.



Dr James de Lemos: Marc, would you like to make some final
comments as we wrap up today?



Dr Marc Ruel: Absolutely. I could not agree more with your
statement, James. I think this is a team effort and I want to be
cognizant to the leadership of Circulation for as the premier
cardiovascular journal, recognizing the importance of
cardiovascular surgery in the field and dedicating an issue
through what is best that's happened over the last academic year
or so. We want this issue to continue for all time. And I think
it's very well started and it's growing nicely. And thanks to the
efforts of many, including of people on this call today. I hope
that our readers will like it and I foresee it will garner
interest even beyond the strict fields of cardiovascular surgery
but to the entire cardiovascular community.



Dr Greg Hundley: This program is copyright American Heart
Association, 2020.