Oct 5, 2020
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.