Circulation November 6, 2018 Issue

James de
Lemos:             
Welcome everyone to Circulation on the Run my name is James de
Lemos, I am the executive editor for Circulation based at UT
Southwestern in Dallas and I will be filling in for Carolyn today
as we discuss this year's surgery themed issue. I would like to
welcome Dr Marc Ruel, the chairman of cardiac surgery at the
University of Ottawa and a long-time editor of the Circulation of
surgery themed issue, as well as Dr Tim Gardner, professor of
cardiac surgery at The University of Pennsylvania and our leader
at Circulation on the editor team for issues related to cardiac
and vascular surgery. Marc and Tim, welcome and thanks for all
your tremendous work in this issue.


Dr Marc Ruel:   
               
Thanks James for having us.


Dr Tim
Gardner:              
Thank you. Glad to be here.


James de
Lemos:             
Why don't we start Marc with your thoughts on how this issue
comes together, how it came to be, you picked the papers and how
we ended up with this terrific issue.


Dr Marc
Ruel:                   
It’s been a really important year for surgery and for this issue,
as some of you may know the supplement which used to be the old
designation of this issue has been changed to the surgery themed
issue in about 2014 or so where the new Circulation leadership
and what we tried to do every year is to bring the very best, not
only of cardiovascular surgical science but also of clinical care
and pearls around clinical and surgical care. So, I think this
year we have had probably more than 60 submissions sent to us.
Tim and I have looked at those very closely and you as well,
James, we really wanted to get the feedback and the approach from
not only cardiac surgeons but also from cardiologists and cardio
vascular care specialist around those. We've tried to select the
best of science and also some papers that we feel would be very
useful with regards to providing new clinical pearls for surgeons
and anyone in the circle of care around cardiovascular surgery.


Dr Tim
Gardner:              
If I could just add, James, of course we have other papers that
have been submitted by surgeons that are published or that deal
with cardiac surgical or vascular surgical topics during the
year, this particular issue is very much focused on cardiac
surgery but throughout the year we have plenty of submissions of
manuscripts by surgeons about surgery about surgically related
topics and so on. So, I am actually kept quite busy reviewing and
commenting and consulting on manuscript submissions of
Circulation. There are plenty of papers over the course of the
year that relate to surgical topics.


James de
Lemos:             
Wonderful, I think you will see, as we talk about these papers,
really that what Marc and Tim are talking about in terms of
papers that are broadly relevant to cardiac surgeons and cardio
vascular providers really rings true. Let’s walk through the
issue, its set up like most of our issues begins with a couple of
opinion pieces, a brief frame of reference, articles about
important topics. Marc, do you want to talk about the Domanski
paper, talk about revascularization for ischemic cardiomyopathy?


Dr Marc
Ruel:                   
Absolutely, we've asked experts, namely Mike Farkouh and Micheal
Domanski, to provide us where their thoughts regarding the
optimal treatment on patients with LV dysfunction and severe
coronary disease. What many of us would call an ischemic
cardiomyopathy, which may be construed as a misnomer or as an
accurate term, I will not debate on this today, but certainly it
remains a very vexing clinical problem. I think we could all
agree that the last niche where we still see very high in terms
of treatment for coronary disease this is probably mortality and
kind of an inability to provide for a tangible result.


                                               
Once LV dysfunction has set in and the present of CAD the
outcomes are poor, and it took years and literally almost ten
years for the STICHES trials to show a benefit for surgical
treatment. This is relatively all study now and it has to be put
in context and I then that Mike and Mike are doing this extremely
well in terms of providing the caveat, for instance, STICHES at
its inception added had a 5% mortality rate around CABG, so we
know that the modern outcome are probably better than that. It’s
very difficult to actually decipher what sound be the mainstay of
treatment for each challenging patient and I think the frame of
reference provided by Dr Farkouh and Domanski is extremely useful
in helping with that.


James de
Lemos:             
Tim we have another frame of reference that is also provocative.
Trying to make a case that we think about in patients with
hypertrophic cardiomyopathy with obstruction early surgical
procedures to relieve the obstruction. Do you want to tell the
readers a little bit about this opinion piece and what your
thoughts on it are?


Dr Tim
Gardner:              
Sure James, this is a really nice frame of reference article from
both doctors Martin and Barry Maron and then their European
contributor Paolo Spirito and the point of their opinion paper is
that the surgical art for managing this very difficult
obstructive cardiomyopathy syndrome has reached the point where
we really shouldn't wait until patients are in extremist or in
class 3 or 4 status in term of syndromic problems and can
consider earlier surgery for these patients. They make the very
important point which I think we have to except is that for
patients to do well with this operation they need to be in a
center where there is experienced surgery and experienced
surgeons, but the point is now that the state of the art for
managing obstructive cardiomyopathy is as such that good result
are obtained and patients should be offered this surgery when
appropriate, but earlier, in order to avoid the challenges of end
stage cardiomyopathy and difficulty relieving the obstruction, so
this is a really important opinion piece. It’s great to see our
cardiology colleagues who are experts in this field make this
point based on well published data from centers like the Mayo
Clinic.


James de
Lemos:             
Moving now to the original articles, we've got 5 original
articles, maybe Marc we can start with your thoughts on 2
articles related to revascularization, one in coronary disease
and one identifying a really novel approach for treating type A
aortic dissection with malperfusion.


Dr Marc
Ruel:                   
I think that's well said James, the first of these original
papers will be likely somewhat controversial. The first author is
Dr Bo Yang and essentially it is a series from Michigan where
they look at just shy of 600 patients with acute Type A Aortic
Dissection, of whom 135 were identified to have malperfusion
syndrome. Essentially defined by the authors as something
slightly different than malperfusion per say but really
malperfusion accompanied with evidence of necrosis in one of the
organs.


Their approach has been new and somewhat controversial in that
they have brought these patients first to the interventional
radiology suite in order to fenestrate in many cases or at least
open the culprit artery or the culprit perfusion territory that
leads to malperfusion syndrome and then depending on how the
patient is doing they would then proceed to open repair as soon
as 24 hours afterwards or they may wait longer in someone where
there is no sign of improvement yet prior to moving to the ER, so
they have found this has not only improved the results with
regards to in hospital mortality after operative repair type A
aortic dissection, but also to allow them to better discern or
differentiate should I say between patients in whom malperfusion
may lead to a futile situation and who then may be avoided from
undergoing a very complex and difficult OR so would argue this is
probably the first such large organized, well documented series
of such an approach and I think it will lead to some head
scratching, this being said it must be remembered that the goal
standard for Type A aortic dissection is dealing with the
intrapericardial aorta first and hoping that the perfusion gets
better from this and everyone knows that the results of this
approach are not fantastic.


We know that even in the best centers, including the latest data
from Germany such an approach has about a 20% mortality rate so
clearly there are ways that we can improve with Type A aortic
dissection and this paper may be a strike in the right direction.


James de
Lemos:             
The other revascularization paper addresses that, I would say
also a quite controversial topic which is how many atrial grafts
are optimal in patients that are undergoing surgical
revascularization?


Dr Marc
Ruel:                   
This is a paper from Toronto where the Ontario ICES database was
used and several papers actually dozens and dozens of papers have
come out previously from this well established and well allocated
database. Steve Fremes who is the senior author and one of his
trainees, Dr Rocha and the team of authors got together and
decided to look at the impact of 3 versus 2 arterial grafts in
patients undergoing cabbage with regards to survival. They have
very nice, very compelling follow up information and they
basically carry out 2 exercises.


First, they wanted to see if the 3,000 patients or so had 3 or
more arterial grafts had a better outcome than the 8,000 patients
or so who had 2 arterial grafts and frankly they found there was
no significant difference with regards to survival at 8 years and
freedom from MACCE at 8 years. However, when they compare those 9
or 8,000 patients or so who had 2 arterial grafts to the rest of
40,000 or so patients who had 1 arterial graft and completions
with veins they found that again there was a survival benefit.
This last finding is not new and its obviously subject to
indication biases as well as expertise bias as we've seen in many
of the observational perspectives studies around multiple
arterial grafting. But I think the concept of comparing 2 versus
3 arterial grafts is very novel in surely in this paper is being
addresses with very high scientific related from the numbers and
the quality of the follow up that's been brought to the exercise.


James de
Lemos:             
I've really been struggling, I love your thoughts and Tim, your
thoughts on how to reconcile the data in space. I really am
having a hard time getting my head around what seems to be
conflicting data about the number of arterial grafts in what an
optimal CABG looks like in 2018 with the evidence that we have.
What are your thoughts on that question?


Dr Tim
Gardner:              
I think that this supports the concept that 2 arterial grafts
whenever possible for some patients, younger patients perhaps 3
but I think the important point is, multiple arterial grafting
should be attempted and carried out whenever possible. I leave
the is 3 better than 2 to some future study or future review that
can be more precise about that.


Dr Marc
Ruel:                   
This being said I think we don't view efficiently coronary
surgery as being an area of expertise and many centers including
very strong academic centers may not necessarily marry the
concept that coronary surgery has to be something with the
dedicated expertise. I think when we look at those observational
perspectives series we see the effect of it may be the expertise
bias, but it may be more than just 2 or 3 arterial grafts, they
may be the whole wrapping of care that comes with it including
optimizing beta blockers and managing diabetes etc. So, I think
it may be more than purely conduits but definitely, as Tim said,
2 arterial grafts are probably better than just 1 and the jury is
still out on whether 3 is better than 2.


James de
Lemos:             
Excellent. Switching gears now Tim, an area that obviously you
have tremendous experience and expertise we've got 2 innovative
papers addressing surgery for individuals who have congenital
heart disease. Can you update us on what we are publishing here?


Dr Tim
Gardner:              
Sure, the one study focuses on the risks of pulmonary valve
surgery in adult patients who underwent a correction of tetralogy
of Fallot earlier in life. This is a growing population actually
we refer to as young adult with congenital heart disease and in
many centers they are more numerous in terms of the patients
groups than infants because this group has been successfully
treated early in life, but this particular group of patients,
patients who have had tetralogy of Fallot repaired and end up
with what the author calls right ventricular outflow disfunction
generally regurgitation through the outflow tract pulmonary valve
sometimes obstruction, these patients then face significant
clinical challenges in death from heart failure, right
ventricular failure or arrhythmias in their late 20's and 30's.
We have been focusing now on the timing and the type of pulmonary
valve replacement.


Dr Tim
Gardner:              
Now there is catheter replacement options available, but when to
do this and how to minimize risk is really the focus of this one
paper that describes a four multi-center study looking at
predictors of risk for these patients. Sort of a hypothesis
generating paper, but it is an important study none the less,
focusing on how to identify patients with right ventricular out
flow tract dysfunction and who should have pulmonary valve
replacement and when that should optimally be done. It a very
good study. The other important study that we have is that the
other age spectrum of neonates and this is a study that is based
on a review of data from the pediatrics heart health information
systems database, led by the group at the Children's Hospital
Philadelphia.


Looking at variations in pre-operative care and management of
neonates with transposition of the great arteries. This was a
little controversial actually when we reviewed it among the
editors because the suggestion is that earlier surgery this would
be in the first week of life and more perhaps aggressive use of
atrial balloon septostomy seems to improve outcomes. This is a
generally low risk population, the point of the paper is that
these pretty good results can be improved by paying more
attention to the timing of surgery and the appropriate use of
balloon septostomy. It’s sort of a quality improvement
perspective based on a large database and I think it’s a very
nice study and undoubtedly creates additional attention to this
particular area.


James de
Lemos:             
Marc, our last original paper is a really novel issue engineering
approach to creating vascular conduits, can you tell the readers
briefly what happens to her in this paper?


Dr Marc
Ruel:                   
Indeed. It’s a paper from Stanford, from Joe Woo’s lab and the
first author is Daniel von Bornstädt. Essentially, as you say
it’s a very innovative novel approach to try to recreate a
bioengineered blood vessel. We surely know there's quite a need
for such off the shelf conduits, not only in cardiac surgery but
also in vascular and vascular surgery and even for things such as
AV fistulas and others. It’s really interesting to see that this
is what I would call transitional science at its best and
surgeons have had an important role over, as you know, centuries
in helping develop this and many discoveries have come from
surgical labs, especially a few decades ago.


In any case, what Joe and his team have performed is to try to
use clinically applicable methods to derive and create a
bioengineered blood vessel and they started first with human
aortic smooth muscles cells and skin fibroblasts which are
literally easy to get and they used those to constructs bi-level
cell sheets, they then used a 22 gauge angiocath needle so that
the sheets would be wrapped around this in order to lead to a
tubular vessel construct. Then the next problem has been
traditionally that those bioengineered vessels would burst out
with atrial pressure. What Joe's team came up with is to use a
commercially available adhesive, so a glue essentially, which is
dermabond which typically we use after any form of surgery to
keep the incision together and they put dermabond on the surface
of this sheet wrapped around an angiocath needle to act as a
temporary external scaffold. They then led this into a bioreactor
and implanted it in series of 20 rats as a femoral artery
interposition graft. The results were excellent. Essentially,
patency was perfect and there was a full vascular maturity with
all 3 layers of blood vessel that you would expect including an
intima that had been formed as a result of the experiment.


I think this is all very promising because none of the methods
here are involving something that would have non-autologous
issues, or you could easily see this being used with a patient’s
own cells in order to achieve an autologous. I think this is
obviously small vessels, there are 22-gauge needle is not a big
conduit, you’re not going to bypass an LED with this, but I think
it’s a start and it’s all done using transitional or clinically
applicable methods. I guess the next step would be moving to a
large animal model and certainly I think we should stay tuned to
see where this leads us.


James de
Lemos:             
I think that's exactly my thinking as well about that discussion
and really leads us into some of the issues that come up in the
review paper that you are a co-author on new strategies for
surgical revascularization. I think this basic in translational
science piece is designed to address some of the limitations of
current revascularization and you all did a really beautiful job
covering some new more clinically ready strategies in your
papers. Can you just tell us very briefly what you all covered in
that review paper?


Dr Marc
Ruel:                   
Indeed, this is a paper that was kind of aiming at being a state
of the art around CABG and rapidly the focus was reshaped towards
kind of new strategies around surgical myocardial
revascularization. Initially we have a section on OPCAB on this
and that and minimizing the inflammatory effects of the pump and
quickly it became apparent that the desire of Circulation and
this themed issue was to focus it more on really what are the up
and coming improvements around surgical coronary
revascularization. This paper focuses on essentially 4 main
areas. One is hybrid coronary revascularization, the second one
is less invasive coronary surgery, the third one is the use of
multiple arterial grafts to which we eluded a little earlier
during this podcast and fourth is the use of an aortic coronary
surgery, essentially meaning bypass surgery performed without any
manipulation of the aorta.


James de
Lemos:             
As we think about innovation in terms of conduits, the procedure
itself, the other aspect that's covered in our last paper is can
we make the procedure safer perhaps by modifying our use of
anti-platelet therapies based on meshment of the platelet
phenotype and Tim do you want to bring us home by just telling us
a little bit about what we learned from Paul Gurbel and his group
of platelet experts?


Dr Tim
Gardner:              
Well we learnt a lot about platelet science and appropriately so
Dr Gurbel is a well-recognized expert in platelet physiology or
platelet management and this is a really quite a challenging area
because many of our patents come to surgery especially for
coronary surgery already on platelet inhibitor agents and what Dr
Gurbel and his co-authors showed in this paper is that although
there is somewhat limited data there can be and should be
platelet function testing and with an appropriate understanding
of platelet inhibition drugs that we may be able to limit the
time between removal of these or discontinuation of these
platelet inhibitor drugs and the necessary surgery which will
improve outcomes and reduce bleeding in patients requiring urgent
CABG surgery. It’s a very useful update and it is a good example
of a paper that isn't written by surgeons, but really applies
very much to the cardiac surgical treatment of coronary artery
disease


James de
Lemos:             
I really like the very practical tables and figures that lay out
the potential tests that surgeons or anesthesiologists may
consider for assessing this and even how one might implement. I
would like to bring us to conclusion now, first I want to
acknowledge, Sara O'Brien at the Circulation office for her
amazing work together with Marc and Tim pulling this issue
together, making sure that we have a consistent high quality
issue with wonderful figures and tables and it really came
together beautifully and thank you both for joining me today and
the podcast I think it’s obvious that we've got an issue that all
of you listen to this podcast need to actually pull out the issue
or download it because we have a co-host of wonderful papers to
look at and cardiac surgery thriving at Circulation. As we've
talked about this is the tip of the iceberg, this themed issue,
we've got great content coming, issue after issue. We are already
open for business next year’s issue, so please send us your best
cardiac surgery research. Please pay attention to these important
papers and apply them in your practice because I think many of
them are already directly applicable.


Marc given your leadership role in the issue do you want to bring
us home and make any concluding remarks?


Dr Marc
Ruel:                   
I think your points are very well taken James and I want to
reintegrate that if I speak on behalf of the cardiovascular
surgical community, we are very thankful to the leadership with
Circulation. James, Joe, Tim and many others and obviously the
support from the staff in clearly establishing that
cardiovascular surgery is a very important therapeutic mentality
and the overall scope in the broad scope of cardiovascular
therapeutics.


Dr Carolyn
Lam:               
You've been listening to Circulation on the Run. Don't forget to
tune in again next week.