Circulation October 2019 Issue

Dr James de Lemos:        My
name is James de Lemos. I'm the executive editor for Circulation
and I'll be filling in today for Carolyn Lam and Greg Hundley,
and delighted to host the podcast for the annual cardiac surgery
themed issue. I'm joined today by Tim Gardner from the University
of Pennsylvania who leads the surgical content in Circulation
year-round, as well as by Dr Marc Ruel, who's the guest editor
for this issue and the Chief of Cardiac Surgery at the University
of Ottawa and has really led the development of this issue. Marc,
Tim, welcome.


Dr Timothy Gardner:      Thank you.


Dr Marc
Ruel:                   
Thank you. Good afternoon.


Dr James de Lemos:        And
Marc, thanks for all you've done to bring this issue home again
this year. It's really wonderful to see this thing develop. Why
don't you start us off and tell us how this issue came together
and what the purpose of this is? Why do we publish a specific
issue focused on cardiac surgery?


Dr Marc
Ruel:                   
We're really delighted that Circulation has taken the stance as
the cardiovascular community's premier cardiovascular journal. I
think as an important piece of this is the fact that
cardiovascular surgery already has a resurgence intermediate with
importance despite new percutaneous options and medical therapies
available. There's more and more patients who find himself in
need advance path if you will, of an advanced cardiovascular
disease and surgery can be performed with safer and better
outcomes constantly.


                                               
So, I think this issue obviously aims to gather the very best of
cardiovascular surgery, not only including cardiac surgery, but
also there's actually one of the papers on peripheral vascular
surgery.


Dr James de Lemos:       
We'll start Tim with you if you don't mind. I'd like to talk
about two papers. One from Stanford that focuses on
inter-facility transfer of Medicare patients with Type A
dissection and then a research letter that studies hospital
volume effects with abdominal aortic aneurysm surgery from
Salvatore Scali and colleagues at the University of Florida. Can
you walk our readers through these papers and lead the discussion
on these?


Dr Timothy Gardner:      The first paper
focused on inter-facility transfer of Medicare recipients with
Type A dissections. First off, underlines the fact that this is a
very difficult, serious condition with mortality rates in this
series there ranging between about 22 and 30%. And the purpose of
the study was to analyze how these Medicare patients with acute
aortic Type A aortic dissections are managed and whether the
effect of high or low volume hospital experiences influences the
mortality. As I think we might expect, patients who receive care
at high volume aortic surgery centers have a lower mortality.
Then the question is, what is the effect of transfer from a low
volume or from a hospital without aortic surgery capabilities?
What is the net effect there? The benefit of care and a high
volume hospital is pretty clear. The mortality rate is
significantly lower and the need to transfer or the actual fact
of transfer does not increase the risk to the patient.


                                               
It's an interesting challenge because we do know that patients
with acute aortic dissection, if their repair or surgery is
delayed, we'll have a predictable accumulating mortality.
However, what this study shows is that the benefit of transfer
and the importance of experience with this complicated aortic
surgery. And it really brings up this very challenging issue of
regionalization, of acute care or specialized care.


                                               
We really struggle with this in so many aspects of surgical care,
medical care in general, but especially procedural care. We
realize that we need to be able to provide emergency care in many
areas and we don't want to suggest that that smaller hospitals
may not be able to care for patients with acute complex
illnesses. But on the other hand, if transfer can be accomplished
and if the availability of high volume experience can be
achieved, that this is something that we really need to look at
carefully. I think that this study brings that into pretty good
view.


Dr Marc
Ruel:                   
James, I think that Tim has already captured the essence of this
paper. The results are impressive in this excellent series and
the really carefully led analysis. This is an important paper and
it's very thought provoking.


                                               
There’re two clans among surgeons. Those that believe that every
cardiac surgeon who was named as such should be able to perform
safely aortic dissection repair and another client and somewhat
sustained or supported by the data from this paper that says that
this is a special expertise that should be or regionalized and
put through centers of excellence. So this paper would support
the latter theory.


Dr James de Lemos:        The
next paper, which was a research letter, sort of adds fuel to
this fire of regionalization, doesn't it? At least insofar as
we're talking about the more complex procedures.


Dr Timothy Gardner:      Yes, this paper
studies the hospital volume effects on surgery for abdominal
aortic aneurysms, an even more common and somewhat less lethal,
but very morbid condition. And this analysis of center volume for
care of these patients is complicated even a little bit more
because as we know, endovascular repair of abdominal aortic
aneurysms is now the most common form of treatment.


                                               
Interestingly, in looking at the outcomes in a variety of centers
with varying volume procedural volumes, there was no difference
in outcomes when endovascular repair was done, but there was
inverse relationship between volume and outcomes after classical
surgical repair. This really highlight a change that's occurring
in vascular surgery where, with endovascular repair being done
more commonly, surgeons are having less exposure unless
experience with open repairs. This is particularly a challenge
for training programs where you have a surgical resident or
fellow for two years and he or she may experience relatively few
open repairs.


                                               
So, this again, the data seems to suggest that higher volume
vascular surgery centers, where the numbers of open repairs are
done, have better results and that this is not nearly as much, in
fact, it wasn't an issue for endovascular treatments, but it
again highlights the procedure of volume outcomes relationship. I
think this is something we're going to have to deal with both in
terms of optimizing patient care, even considering when we're
training new or young avascular surgeons, they may have to move
to different centers to ensure that they have the kind of
exposure to classical surgical treatment for those complex
patients who are not candidates for endovascular repair.


Dr James de Lemos:       
Let's change gears. We've been talking about two systems of care
issues, but let's get back to the complicated patient themselves
and talk about a paper Mark from Kato and Pellikka from Mayo
Clinic, focusing on hemodynamic and prognostic impact of
concomitant mitral stenosis in patients undergoing surgery or
TAVR for Aortic Stenosis.


Dr Marc
Ruel:                   
As you say, this is an intricate clinical problem that we not
uncommonly meet when we provide care for patients who have severe
aortic stenosis. These are not young patients. These patients in
this particular series of 190 patients with severe aortic
stenosis, they also had some significant degree of mitral
stenosis. These are patients that had a mean age of 76 years. I
think we've all encountered these patients estimations, so
someone has severe aortic stenosis and has some form of calcific
mitral stenosis. And indeed in this series, more often than not,
the vast majority of those patients had calcific MS as opposed to
a Rheumatic MS. So, a different type of pathology probably to
what we see in the elderly patients coming in with some degree of
inflow obstruction.


                                               
So, the authors took their 190 patients, mostly from the Mayo
clinic, but also from Tokyo, about five patients contributed from
Japan, and matched in one to two with some controls who also had
the same degree of severe aortic stenosis, the same age, same
gender, same left ventricular ejection fraction, but didn't have
mitral stenosis. And then compare their fate over a couple of
years. Essentially, what the authors found is that in patients
with severe MS, which was defined as a trans-mitral gradient of
equal or higher than four millimeters of mercury, the midterm
survival was decreased. The hazard of death was increased by
about 90% or so. And there was also a classification, the sub
classification based on the fate of the patient with regards to
the echocardiographic findings, as to whether the patient truly
had mitral stenosis at the time of presentation. So prior to the
aortic valve replacement or whether the patient had pseudo-mitral
stenosis. How the authors classify this, is those patients in
whom the mitral valve area remained less than two centimeters
square before and after aortic valve replacement were classified
as having true mitral stenosis.


                                               
The authors provide a number of maybe predictors, if you will, or
correlates perhaps a more appropriately termed as such, of
patients who would be generally believed as having true mitral
stenosis. And these included, for instance, in the mitral valve
area was less than 1.5 centimeters square at the time of
presentation, if calcium involved at both the anterior and the
posterior leaflet on echo. And there was also the concept of
Andler excursion. So, basically the distance between the apex and
the analyst of the mitral Valve, half of the patients had true
mitral stenosis and the other half saw an increase in the mitral
valve area above two centimeters squares after aortic valve
replacement.


                                               
I think still that we don't have an answer to the question as to
whether the mitral valve should already be intervened upon in
this series. It was an observational series, so there's no arm
where the mitral valve was actually intervened on, and we know
that often this intervention is not easy to do if it's by TAVR,
there's not a lot we can do on the aortic valve and if it's at
surgery, often these patients may have extensive mitral annular
calcification, which is not an easy undertaking to fix at the
time of surgery.


                                               
So, whether these patients, even the ones with true MS are better
served by just addressing the aortic valve or adding a mitral
valve intervention in addition to the AS treatment still remains
an unresolved or unanswered question. But I think this paper
helps tremendously with regards to identifying patients who may
have the true mitral stenosis concomitant problem at the time of
presentation with a severe AS.


Dr James de Lemos:        This
was news for me actually. The high prevalence of pseudo MS in
this context, I think many of us are very familiar with this with
aortic stenosis and low output, but to see this in the context of
serial valve lesions was really instructive for me. Tim, what are
your thoughts?


Dr Timothy Gardner:      I think this is
a really important observation to remind ourselves of in this
TAVR era. If you have the heart open and you're doing the aortic
valve replacement and you notice this, you can get a picture of
this severity of the mitral stenosis or the mitral valve
involvement, but I think that in the TAVR era, this finding, this
possibility of significant mitral stenosis related to a more
severe aortic stenosis has to be accounted for and taken into
account.


Dr James de Lemos:       
Excellent. The next paper I'd like to talk about is another
original article from Shudo and Joe Wu at Stanford. Remarkable
series really of almost a thousand heart-lung transplants that
were done and reported in UNOS. Tim, can you walk us through this
paper and its implications?


Dr Timothy Gardner:      heart-lung
transplantation was done first at Stanford and actually by one of
my close colleagues. Bruce Reitz in 1981. It was a really an
operation and in the tradition of the innovation there in
transplant surgery at Stanford. The operation, primarily for
patients with end stage lung and heart disease, was done
reasonably often at adventuresome and well-experienced transplant
centers in the eighties and nineties and it's used less often
today because we found that even in patients with end stage lung
disease and concomitant ventricular failure that many of those
patients can be treated successfully with double lung
transplantation.


                                               
So, that has resulted in a decline in use of heart-lung block
transplantation. The other problem is that as they mentioned in
the article that a donor becomes available and you can get two or
three patients treated by taking the individual lungs and the
heart for three recipients rather than using the whole block for
one. That's been another reason why it's been harder to get these
heart-lung blocks. But for some patients with end stage heart
disease and irretrievable lung disease, this is a great option.
There's a few patients with end stage congenital heart disease
who have developed irretrievable Eisenmenger's complex with
severe pulmonary irreversible form of hypertension who are still
candidates for this, but this analysis of the 30 year experience
at Stanford and using the UNOS database as well is very
interesting and shows the importance of donor selection as a
really significant effector of outcomes.


Dr James de Lemos:       
Yeah, well I was also struck by the recipient factors too. It
looks like selection in both directions is so important. The
group that was remarkable to me was the markedly poor outcomes in
the group that had heart-lung transplant after ECMO, that five
times increase in mortality. That really struck a chord,
particularly given what we're seeing now with ECMO accelerating
somebody's status on wait lists. I don't know Mark or Tim, do you
want to comment?


Dr Timothy Gardner:      That's a very
useful observation and where an individual patient ends up on the
acuity list as a potential recipient with UNOS rules, it is ECMO
support does get them to a higher level of urgency and yet, as is
shown in this series, the morbidities or co-morbidities
associated with a patient who requires ECMO support prior to
transplantation is pretty consequential. And as you said, those
were the features of the recipient, the degree of co-morbidities
or co-morbidity complications also impact the outcome.


                                               
We're still struggling to find the best way to deal with rescue
patients both with mechanical support and with transplantation,
organ transplantation, and even in the case of heart failure,
with destination therapy with mechanical devices, we're still
struggling in an area where the challenges are high, and the best
practices are not always as well clarified as we would like.


Dr Marc
Ruel:                   
And I would echo those concerns. I think the prohibitive results
that we see after ECMO reflect the reality that there's not a lot
of intermediate therapies available for patients who require
heart-lung transplants. We have them for the heart now. We can
move from ECMO and not go directly to an LVAD or to a transplant
because we have implantable axial devices that can be put in
percutaneously and basically can arrest the inflammatory response
and the major cascade derangements that we see with ECMO.


                                               
Unfortunately that is not available to replace both the heart and
lungs, so I think there's still some medical advances, surgical
advances that are necessary to bridge the gap because that gap
right now is real and it's not a gap, it's a cliff.


Dr James de Lemos:       
Great discussion gentlemen. Let's talk next Marc, about a
research letter that was a case series from Cleveland Clinic from
Donnellan and Desai, focusing on a fairly large group of
individuals that had received mediastinal radiation therapy
previously and then underwent valve surgery for radiation-induced
valve disease.


Dr Marc
Ruel:                   
We were happy to receive this research letter from the Cleveland
Clinic because clearly that institution, and maybe a few others
around the world, have a special expertise in dealing with the
uncommon, but very, very challenging issue of patients with the
surgical radiation-induced mitral valve disease. And in fact,
radiation-induced carditis. On average, these were patients who
were seen about 17 years after their chest irradiation and I
guess the main message that can be seen from this paper is that
there's often multiple cardiac issues in those patients. They
don't just have, for instance, a single valve, in this case the
mitral valve, being affected. But the vast majority all tolled of
around 80, 85% of patients required not only either another
valve, but valve plus bypass or bypass surgery to be performed as
well.


                                               
So, there are clearly patients where there's been a lot of
physical/irradiation damage, not only to the mitral valve, but to
the entire heart. It's also, when you look at this series of
these 146 patients, you can see that many had an increase in the
right ventricular systolic pressure on echo and probably some
degree of RV dysfunction as certainly we've seen episodically in
our practices.


                                               
So, hospital mortality outcomes are pretty good, but the results
are humbling. 51% mortality at 2.8 years. And these patients were
on average 60 years of age. So looking at U.S. life tables, when
someone's 60 years, I've made it to 60, they usually have at
least another 20 years on average to live. But these unfortunate
patients, despite their cardiac operation performed, having been
performed safely, have about an 18% death rate per year.


                                               
I think the jury's still out as to which are clear indications to
offer these patients surgeries with the humbling results that we
see even at a center of excellence by the Cleveland Clinic. But I
think this is a foray into a very difficult cardiac problem for
which there was limited literature before and certainly that's
something that's very relevant as we refer to very advanced
cardiac surgical therapies for patients with advanced disease.


Dr James de Lemos:       
Mark, you're actually a coauthor on our State-of-the-Art piece,
evaluating arterial grafts and CABG, reviewing after the
publication of art and radial. What were the main conclusions
from your review and interpretation?


Dr Marc
Ruel:                   
Essentially, there's a discrepancy right now with regards to the
use of multiple arterial grafting. The observational series have
almost uniformly showed that patients who receive multiple
arterial grafts live longer and do better, et cetera, but I think
this has to be taken for what it is. There's an inherent
indication bias or confounding by indication that goes into
allocating that therapy to patients who are perceived to have the
potential to do well in the long-term. There may also be an
expertise bias at the institutions that provide this and those
patients may be receiving better secondary medical therapy or
guidelines directed medical therapy, etc. So, maybe a halo effect
that comes into play.


                                               
In counterpart, the randomized control trials of which the latest
was the arterial revascularization trial. Now available with data
at 10 years, have shown essentially very little difference which
regards to the use of multiple arterial grafts on long-term
outcomes. Even looking at cardiac-specific outcomes like
myocardial infarction. Actually the more compelling data came
from their Radial Alliance, also led by Mario Gaudino who is the
author of this, State of the Art paper.


                                               
The conclusion of the article is that we need a trial and we need
to include the radial artery. The answer may not necessarily lie
with the use of mammary arteries, but it may be that the radial
artery is more user friendly and more robust. So the new ROMA
trial has been designed with that in mind. Comparing one arterial
graft versus as many arterial grafts, as long as it's more than
one in the test group that the surgeon wants to use. And the
surgeon, she or he can use the right internal thoracic artery or
radial artery in order to complete the revascularization.


                                               
That trial is ongoing. Enrollment is on track and hopefully
should provide answers to this very relevant question.


Dr James de Lemos:        You
know that discussion about the limitations of clinical trials,
Tim, I think leads really nicely into the frame of reference you
received from Eugene Blackstone and Cleveland Clinic, doesn't it?


Dr Timothy Gardner:      Yeah, and it
was really an article worth everybody reading. It's a short
opinion piece and he points out the fact that we really have
competing standards for choosing therapy. Sort of the standard
traditional evidence based medicine, evidence-based medical care
versus precision medicine which focuses on individual patients
risk factors and so on. It's sort of the average treatment effect
that we may be able to demonstrate well in randomized clinical
trials versus real world experience with various therapies based
on the risk profile of the patient. It's a really excellent
article and as many of us know Gene Blackstone is a very
thoughtful student of statistics in surgery and this is, I think,
an excellent article. I'm really grateful for his doing this
opinion piece for us.


Dr James de Lemos:        The
last opinion piece we have is from Mike Farkouh in the group in
Toronto. Can you just give the readers and listeners a bullet
about what they might expect in that piece?


Dr Marc
Ruel:                   
I think it's one of the remaining big questions, if you will, in
myocardial revascularization as to what should be done with
diabetic patients in multi-vessel coronary artery disease who
have an acute coronary syndrome and require revascularization. A
very well written piece and certainly that instructs what
probably the next five years we'll see in terms of big study
questions in coronary REVASC.


Dr James de Lemos:       
First I'd like to recognize Sarah O'Brien from the Circulation
Editorial Office for her tremendous work for pulling this issue
together. She's really the glue that brings this issue together
every year and thank as well Marc, for your leadership again of
this effort and Tim for your ongoing leadership at circulation
with our cardiac content and vascular content as well as
liaisoning with our surgical colleagues.


                                               
Dr Marc, you get the last word. Can you please summarize the
thoughts you'd like to leave our listeners with?


Dr Marc
Ruel:                   
Thank you, James, for your generous comments and also for your
support of cardiovascular surgery in and of the team issue. I
think again, we have a fantastic issue this year and we really
want to gather the very best of cardiovascular surgery and we
want to get the highest impact papers. Circulation is home for
the best data, the best outcome, say the most interesting answers
to important clinical questions that are around cardiovascular
surgery.


                                               
There's definitely an editorial desire to help with the best of
cardiovascular surgery science. And I think I want to again
launch a call to cardiac surgical investigators and
cardiovascular and surgical investigators in general to consider
circulation as your home.


Dr Timothy Gardner:      Yes. And if I
could just add to that, not only are we interested in a
surgery-themed issue annually that really highlights some of the
best articles that we have to publish, but we also want some of
the best surgery science during the course of the year. And just
remind our surgeon colleagues that the particular advantage to
having a paper published in circulation is the exposure of that
study to a broad cardiovascular community. Not just surgeons, the
predominant readership obviously of circulation, or cardiologists
and other cardiovascular specialists. So that's the big advantage
you get by having your best work published in circulation. We'd
love to see more of it.


Dr Carolyn
Lam:               
This program is copyright American Heart Association 2019.