Circulation October 25, 2022 Issue

This week, please join Circulation's Associate Editor
Marc Ruel and Executive Editor James de Lemos as they summarize
all of the articles found in Circulation's annual Cardiovascular
Surgery-Themed Issue for 2022.


Dr. James de Lemos:


Hi, welcome to Circulation on the Run. Greg and Carolyn are off
today. My name is James de Lemos. I'm the executive editor for
Circulation and I'm delighted to be joined today by Marc Ruel,
who's the editor of our themed issue on cardiac surgery and leads
the development and curation of all of the cardiac surgery
content in Circulation. Marc, congratulations to you, to Mike
Fischbein, to the whole Circ team on another spectacular effort
to pull together this issue. Glad to have you here today.


Dr. Marc Ruel:


Well, thank you very much, James. It's really a team effort. I
want to salute and thank the vision of Circulation to really give
an important component to surgical science. As you often hear me
say, your surgery provides the most durable and robust solution
for advanced heart disease, right? So it's a very important part
of the mission of Circulation as the premier cardiovascular
journal. I want to thank you and also Joe Hill, our
Editor-in-Chief and obviously the entire team of Circulation as
well as all staff. Augie [Rivera], who is helping us on this call
as well as Nick [Murphy] and many others who have made this issue
possible.


Dr. James de Lemos:


Well, great. Well, let's get to this. And you recognize as well
Mike Fischbein, who's the Cardiac Investor surgeon at Stanford
who helps to edit the themed issue and really helps us to think
about basic science into surgical specialties. Let me start,
Marc, with cardiac bypass surgery. We have actually three papers
in this issue that cover various aspects of CABG. The first one
is one that you and I really resonated with, I know, because we
talked about this. It's a paper by Ono from the SYNTAX Extended
Survival study titled "Impact of Patient Reported and
Pre-Procedural Physical and Mental Health on 10 year Mortality
after PCI or CABG." And this is a really fascinating paper,
looked at obviously patients with left main or multi vessels
coronary disease, but used objective measures of physical and
mental function from the SF-36 score and calculated summary
physical and mental component scores.


And then used those scores to evaluate whether there were
treatment interactions based on physical and mental performance
metrics with regard to the benefit of CABG over PCI. And really
fascinating, first that there was an interaction and that the
magnitude of benefit of CABG over PCI for multi vessel disease
was substantially greater among individuals that had higher
physical performance as well as mental health performance. What
did you think of this paper and data? I know you wrote a
tremendous editorial to this. So this is something that you
thought about as we were bringing the paper in, but also had to
think about in terms of putting this paper in the context of this
daily decision for patients with multi vessel disease.


Dr. Marc Ruel:


Thanks James. And I agree with you. I think this is a bit of a
new paradigm, right, to really think of the individual patient
decision. It's a form of precision medicine if you will, with
regards in this case to physical functioning and mental
functioning prior to something as invasive as undergoing CABG. So
I want to thank you, the Circulation leadership for inviting Anne
Williams who's a cardiologist and yours truly to write a tutorial
on this piece because I do think you, that is really, it is
something that's quite intriguing and it makes sense. I think it
is intuitive. I think clinicians who send patients to CABG and
see them come back and hopefully in a good state, the very vast
majority of the time, do realize nevertheless that CABG is a very
invasive procedure. So the patient has to be actively involved in
her or his recovery.


And interestingly as you pointed out, there's quite a effect
modification if you will, between the benefits of CABG over PCI
in the SYNTAX trial, which many will remember as having
randomized either left main or three vessel disease, coronary
artery disease patients to PCI versus CABG. So there was an
effect modification in those patients who had better functioning,
not only physical, but interestingly, even more so mental
component score of the SF-36 prior to operation. These patients
would derive a greater benefit from having been randomized to
CABG over PCI. So I think this is obviously logical, it makes
sense and the converse will be true, but it's nice to see it
formalized, to my knowledge, for the first time in the context of
a rigorous randomized control trial such as SYNTAX with a
long-term follow up.


Now obviously this, like any study, there are a few caveats. Not
every single patient had their SF-36 at baseline, but roughly
about 90 plus percent of patients did. And I think that is quite
an important clinical lesson in terms of allocating PCI versus
CBG... I've often said over the years as a division head and
someone who performs this operation often to my more junior
colleagues, "Don't perform bypass surgery if someone's not going
to live five years." That might be a bit of a simplistic approach
but the data and the conclusions from this paper would support
that. It's probably not too farfetched to think as such.


Dr. James de Lemos:


I think that's a great point and your clinical experience is so
valuable for us here. One question I have is, do you think that
it would be advantageous to objectively measure these parameters
or is this something that the heart team or the surgeon at the
bedside can assess intuitively? Because I think that's the
question, right? Is this something... It certainly fits with what
we would expect intuitively, that the more complete and durable
procedure works better in people that are more robust physically,
mentally. But should we be measuring this preoperatively to help
make that decision or should this be a intuitive decision by
expert clinicians?


Dr. Marc Ruel:


It's a great question and I think it's one that's not yet
answered. I mean, the data from the paper would suggest that it
has to be a formalized physical component score and mental
component score and then ready allocate according to turnstiles.
But that being said, we all know that we can address those issues
by an end of bed type of eyeball test, right? So I think you're
absolutely right. It may be that a clinical expert may provide
the same type of information. Unfortunately we don't have that
from the paper but I think there will be several subsequent
papers that will look at this.


I think we are in the era of precision medicine and one would
even think, why has this not been done before considering how
invasive bypass surgery is? You guys, you cardiologists and
primary care physicians all know that it takes patients six to 12
months to be recover from sternal bypass surgery. Surgeons all
be, I'll say that with a blink in my eye, don't always
necessarily always see that, right? And think that's more like a
one to three months but the data would suggest including that
from randomized controlled trials such as Feedem, that it takes
six to 12 months. So it's been one of my career long quest if you
will, to make bypass surgery less invasive. And I think this type
of paper really provides the impetus to do so.


Dr. James de Lemos:


Well, thanks. Let's shift gears from a study that makes perfect
sense and fits our preconceived notions to maybe one that
doesn't. And this is a research letter from a group led by Steve
Goldman at University of Arizona looking at long term mortality
from the VA study comparing radial arteries with saphenous vein
conduits in CABG. And this looked at long term mortality from
this study, which included over 700 individuals that had extended
follow up beyond 10 years. At one year, the cath data had not
shown differences in patency in this study, I think important to
interpret, but they find absolutely no difference in mortality
within similar median survival of 14 to 15 years after CABG in
this study. This was controversial among the editors when we
discussed it, but what are your thoughts about these data and how
this informs the radial artery question in CABG?


Dr. Marc Ruel:


Absolutely. You are so right in seeing that this was
controversial because there are in fact two ways to look at this
paper, right? You can drain the information that's in there or
you can be a naysayer. And there's credence to both approaches,
in my opinion. One could say, "Well, there was no difference at
one year in terms of graph patency, so why would there be one at
14-15 years?" Well, the answer to that would be the durability of
the compared conduits would be potentially different, right? One
to five years is what we call the "golden age of saphenous vein
grafts." And beyond that time period, one could perhaps expect
that the radial artery would do better and start translating into
clinical benefits. But that was not seen in this long-term
analysis of the VA RCT that compared the use of a saphenous vein
versus a radial artery.


The other way to perhaps find why the data is discrepant versus
the methodology that had been performed before showing an
advantage for the radial artery, would be that this is more
perhaps of a real world type of experience. It comes from VA
centers. Perhaps the expertise or the level of penetrance if you
will, of use of the radial artery was not the same as other
centers that maybe more "academic" and more vested into using the
radial. So it's possible that those could have played a
difference in nullifying if you will, the results of radial
artery. But I nevertheless think that it's very important data.
It makes us think and it is the largest single series data
available that compares the radial to saphenous vein in a
randomized control setting. So one cannot ignore it, and I think
it's a very important piece of information that strengthens the
surgery themed dish.


Dr. James de Lemos:


Thank you, Marc. And then the last CABG related article that I'd
like to talk about is the prospective piece by Mario Gaudino and
Bruce Lytle discussing the right internal thoracic artery for
bypass. Asking the question, did we get it wrong? And this is
really a very interesting piece. I encourage our readers to look
at. That attempts really to reconcile the strong promise of the
RITA with the disappointing results from art and the higher than
expected failure rates in other trials. And what the authors do
here really resonates with, Marc some of your points about
individualizing treatment.


They point out that some of the worse than expected RITA results
may reflect the artery to which the RITA has been anecimosed,
simply that results when an anecimosed to non-LED targets aren't
as good and potentially the experience of the operators. Their
final conclusion really isn't that, the reader's not a superior
conduit but that perhaps more individualization, both at the
patient level but also based on physician experience, maybe
what's needed to achieve the optimal selection of conduits and
bypass results. What did you think of this? How did their
conclusions and interpretation resonate with you?


Dr. Marc Ruel:


I agree with your summary James and I think you are spot on.
What's interesting in addition from this frame of reference is
that it unites the opinions of two key opinion leaders, i.e Mario
Gaudino, who's essentially behind much of the data favoring the
radial artery over the use of the saphenous vein. And Bruce
Lytle, who historically was behind really proposing the use of
the right internal thoracic artery and this bilateral ITA
grafting if you will, and they are really coming together and
putting their thoughts in a really sensible manner with regards
to the points that you raised already. I would add in my own
opinion, it's twofold. One, there's nothing biologically wrong
with the right internal thoracic artery. So if the LITA works,
the RITA should work as well from a biologic point of view. In
fact, surgeons know that it's often bigger than the left internal
thoracic artery and even more suitable or suited as account with.


What might be wrong is the applicability of it and that question
really goes in a couple of important manners. Let's remember
surgery is a craft, right? And it's a bit different. It's
something I like to repeat, and it's not always captured. It's
not really a pure science, like for instance, giving atorvastatin
40 milligrams would be this much more variability. And if you
allow me a ten second example, if you were to take one of the
bronze tools from Rodin, a grape sculptures, and take it away
from him, the sculptures would not be as good. But if you were to
give that tool to all semi-professional sculptures around the
globe, the United States or France for instance, you may not see
any benefit from that tool. So again, the crafty example of
surgery is something that we have to compose with all the time.


So the RITA is a great conduit, but it's often not onto the LED
per se. And we know that LED in an average patient, which doesn't
exist, it's probably about 50% of the left heart profusion. So
really the LITA has an advantage from that point of view. And
when we compare studies that have used the RITA on a non LED
target, there are in some cases bound to fail or at least be
neutral. So I think the jury's still out but really the
perspective that's denoted here, as you said, is a fascinating
one coming from two key opinion leaders, each in their camp of
radial versus right internal thoracic artery use.


Dr. James de Lemos:


Well, fabulous discussion, Marc. I really appreciate your
insights. I think as cardiologists, the decision making about
conduits can often be opaque, and this is really insightful.
Let's switch gears and talk about valve surgery. We have two
papers on valve surgery. First, an original research article by
Johan Wedin from Uppsala on bicuspid aortic stenosis
demonstrating adverse ventricular remodeling and impaired cardiac
function prior to surgery with a heightened risk of postoperative
heart failure. This is a really interesting study that looked at
271 patients that were undergoing surgical aortic valve
replacement.


About half with bicuspid valves and half with tricuspid aortic
valves, and they did comprehensive preoperative echo-cardiography
and then followed the patients for four to five years after
followup. And despite the expected finding that the bicuspid
patients for younger, they had a substantially worse LV echo
parameters pre-op with greater LV wall fitness, greater LV mass,
worse preoperative LV function. And that translated even after
successful AVR into increased risks for postoperative heart
failure hospitalizations when compared to individuals with
tricuspid aortic valves. And so the authors conclude that at
least in contemporary practice, perhaps individuals are
undergoing surgery for bicuspid aortic valve stenosis relatively
later in the natural history, and they might merit closer
civilians and possibly earlier intervention. What did you think
of these data and do they make you think about your timing of
recommendation for surgery with bicuspid aortic stenosis?


Dr. Marc Ruel:


Absolutely, and thank you James. I think this is very much in
line with the current precision medicine led trends of operating
earlier on patients with aortic stenosis. I think this is another
subgroup that really deserves our attention. I think there are
two things at play here with regards to patients who would have a
comparable degree of hemodynamic aortic stenosis, either coming
from a bicuspid aortic valve phenotype versus a normal tricuspid
aortic valve phenotype. And I think the two important differences
are, first, often the bicuspid valves are more prone to have a
mixed disease and being more calcified as well. We often see
surgery, what I call these black valves, like the valve is so
calcified and necrotic that it actually turns black or navy blue
in color. And this is not an uncommon finding in younger patients
typically than tricuspid aortic valve patients.


The second thing is that we have to remember that bicuspid aortic
valve disease is a lifelong illness. So these patients often go
undetected for a very long time. They may be 55 years old
compared to someone who's 68 and have the same degree of
hemodynamic aortic stenosis and even AI. But the disease has
really, in the bicuspid aortic valve patient, has probably been
there for decades, sometimes even the whole life. So I think the
effects on the left ventricle are destined to be worse, and also
in terms of recovery after resection and after aortic valve
replacement. So I think these are humbling tidbits that come from
this paper that really even allow us in this era of early TAVR
and now two randomized trials that have looked... One from Europe
and one from Korea that have looked at asymptomatic aortic valve
replacement interventions with favorable results towards early
intervention. That really tell us that we should pay even closer
attention to those patients with bicuspid aortic valve
phenotypes.


Dr. James de Lemos:


Thanks, Marc.


And the second valve related paper is a prospective piece by
[Rebecca] Becky Hahn, Vincent Chan and David Adams, evaluating
current indications for a transcatheter edged edge repair of the
mitral valve for primary mitral regurgitation. I thought this was
a really well done piece and one that I appreciated focus
specifically on primary micro-regurgitation. The piece includes a
terrific algorithm for clinicians that really helps to guide
decision making through a multidisciplinary approach.


They talk about the importance of specialized valve imagers,
given the complexity of evaluating even the etiology of
micro-regurgitation. The importance of excellence in determining
the quantitation of severe MR, valve morphology and dimensions.
And then really take it a step further to drive decision makings
based on risk assessment of the patient. Obviously for primary MR
for adequate surgical risk patients surgery is recommended, but
then it walks through the decision making for which of the
patients that are not surgical candidates might be optimal
candidates for transcatheter techniques. How do you think this
field's moving and how did this perspective change your thinking?


Dr. Marc Ruel:


This is such an excellent piece as you denoted. I think it really
comes from three experts in the field representing different
school of thoughts, if you will. One, more hybrid, more catheter
based and more surgery based. And I think the jury's still out on
transcatheter edge to edge repair, especially for primary
marginal regurgitation. It's paradoxical as we're hoping that
edge to edge repair would be primarily used in secondary MR and
have great results. We now know and somewhat humbling, that it
works not as great as we were hoping for secondary MR and it
seems to be working pretty well where we already had a fantastic
surgical therapy for it, which is essentially primary MR and
Fibroelastic Deficiency type of lesions. Now, as you know, these
patients do extremely well with surgery. There are several series
of 800, 900, a thousand patients operated either conventionally
or minimal invasively with maybe one death. Still one too much I
would argue, but extremely low risks.


These are the healthiest patients that a cardiac surgeon often
can operate because I would argue this probably an inverse
correlation with coronary artery and peripheral vascular disease
in those patients. It's hard to know. There's some elements of
the answer that we don't have yet. What about the very long term
follow up? What about 10 years? What happens when an edge to edge
repair fails and it was for primary MR in a younger patient?


And I think the authors really captured those very important
caveats quite elegantly and provide a very balanced view. So like
you, I'm very happy with this piece. Lastly, I'll conclude by
saying there's even controversy as to sub-clinical parameters
with edge to edge versus surgical mitral valve pair for primary
MR. What does two plus mitral regurgitation that is
post-procedure, What does that mean? Is this something that's
going to impact the patient at 10 years, at 20 years and perhaps
churn, what was it initially, a great therapeutic solution into
one that's not so desirable? So again, as I said, the jury's
still out on this and I think these really captures the main
element of the answer as we know them in 2022.


Dr. James de Lemos:


Excellent points. I think really, I love your conclusion that
hopefully there will be a better transcatheter solution than this
for patients that aren't surgical candidates, obviously, because
it doesn't, unlike TAVR, this doesn't come close to matching the
surgical option. The last couple of papers in the issue focus on
putting cardiac surgery in the greater context of the patient
experience and the healthcare system experience and are in the
health services research phase. The first one is from
multi-centered team led by Amgad Mentias at Cleveland Clinic and
Ambarish Pandey at UT Southwestern. And it focuses on a new
performance metric that they're calling, 90 day risk standardized
home time for cardiac surgery hospitals in the US.


And this group has done several studies with this new metric that
basically is attempting to evaluate performance at the patient
level with a very patient-centric metric of how much time they
spend at home. They've published previously using data from heart
failure patients and post MI patients and now are extending this
to cardiac surgery and using risk adjustment of time outside the
hospital in the 90 days after surgery to evaluate the variability
among cardiac surgical programs. And they find that the metric
correlates with mortality and readmission, that higher volume
surgical centers are associated with more time spent out of the
hospital.


And then when they compare it more directly with approaches that
are used to currently rank performance, they see that this
results in some reclassification of performance categories versus
the other metrics. It's early in the life of this new metric but
I'm interested to see intuitively is a cardiac surgeon, how does
another tool to evaluate your performance, your team's
performance and your hospital's performance resonate? And does
this have any intrinsic advantages to you over the other risk
standardized tools that are currently being used? Certainly in
the US I don't know what's happening in Canada.


Dr. Marc Ruel:


Great points, James and I agree, this is an impressive data set.
It's almost on 1 million patients from more than 1000 centers in
the US. And as you said, it is a new patient based metric. It's a
bit of a patient before the outcome if you will, those PROs that
are so more commonly now the object of research with regards to
outcomes. I would somewhat simplistically say that there are
three possible outcomes to any heart surgery, patient survives
and feels better. That's number one, that's what we want to
achieve for everybody. Unfortunately, there are two other
outcomes that can happen. Patient survives but patient is not
improved by the surgery or has a complication as a result of it
and quality of life does not improve. And third, obviously the
one that is the obvious, highly detrimental is that patient does
not make it from the surgery.


But I think really what this paper highlights is the importance
of really focusing on the first one by the number of days spent
at home during the first 90 days post intervention, post-surgery
itself. So I think it is really a marker of how well the
patient's doing. It closes the loop, if you will, with the first
paper that we looked at, in an observational large data set type
of way. But it again calls to, how was the patient functioning
pre-op? And that data, as we know, is not available from this
series. So it could be three things essentially. It could be
performance and definitely it pleases the mind to think that the
performance of the institution i.e, the quality of the care
provided has a huge impact. But it could also be two other
things.


It could be the level of functioning of the patient. The ability
to get back and spend many of those first 90 days at home versus
not, of the patient himself or herself, depending on the various
populations that are served by those institutions. And third, it
could also be a little bit of a recurrent theme of mine and I
apologize for that, but it could be the degree of invasiveness
that's provided if you out of surgeries offered to these
patients. So I think these are interesting paradigms. They are
very important. Again, they're completely in line with precision
medicine and I think that this performance measure, as you
alluded to, is an important point because a patient who survives
but doesn't go back home really is not deriving a benefit from
any operation.


Dr. James de Lemos:


Yeah, great points. And I think this discussion really leads us
into our discussion, the last paper, which is another paper that
attempts to put surgery in the greater context of the population
and environment in which patients come. And this is led by Aditya
Sengupta and her team from Boston Children's Hospital evaluating
contemporary socioeconomic and childhood opportunity disparities
in congenital heart surgery. This is a really next level analysis
of associations between socioeconomic status and outcomes after
congenital heart disease surgery in children focusing in one high
volume quaternary center in Boston. And what they did is
developed a novel predictor that was a US census tract based
nationally normed composite metric of contemporary childhood,
what they called neighborhood opportunity. And this comprised 29
indicators across three domains.


The three domains were education, health, and environment and
socioeconomic domains. And they classified the patients into very
low, low, moderate, high and very high neighborhood opportunity.
And then they looked at evaluations across multiple outcomes.
They did not see any association of neighborhood opportunity with
early deaths, which I think is encouraging, but they did see that
children with lower neighborhood opportunity had longer length of
stay, higher healthcare costs and then significantly higher late
deaths following surgery when the multiple components of long
term care of these children probably have time to operationalize.
I found this sobering and a complex message that excellent
cardiac surgery can deliver superb outcomes across all levels of
opportunity but if these issues aren't addressed, there are
financial implications, but more importantly, the long term
benefits of the cardiac surgical procedures aren't fully
realized. Interested to hear your thoughts on this and how this
might apply more broadly even to adult surgery.


Dr. Marc Ruel:


I agree, James and I too, really love this paper. As you say, it
is sobering. It's a paper for physicians, but I would argue it's
probably bedtime reading for Mr. Biden, any other country leaders
as well. Whether it's Mr. Macron or Mr. Trudeau. Definitely
something that is shows that what happens after the hospital
stay, even in something as complex as congenital heart surgery,
performed at Boston children, obviously a great institution. But
what is shown here is that the institution with its top quality
outcomes as we know them to be, is a fantastic societal and
outcome equalizer, if you will. But once that passage through the
tertiary or coronary institution has occurred, then reality sets
in. And the childhood opportunity index that the authors had
previously published in JAMA proves to be, again, a very
important predictor of how these kids do later on. So this refers
really to the societal contract that we're all part of as
physicians. And we obviously, a big part of our mission is to
improve the outcomes in hospital, but also beyond it. And I think
this paper illustrates this very nicely as you so eloquently
summarized.


Dr. James de Lemos:


Well, thanks. And I'll just, before I hand it over to you to
conclude and wrap up, just compliment you and Mike and the entire
team, as well as the authors who have submitted not just these
but so many other superb papers covering the full spectrum of
surgical sciences Circulation. I'm proud for us to have the
opportunity to share these terrific papers with our readers and
with researchers. And congratulations again to you for pulling
this together.


Dr. Marc Ruel:


Well, you're very kind and thank you, James. To you and Joe,
Darren and our and entire editorial leadership for the important
place given to surgery within Circulation. It's something that I
believe is important and resonates with surgeons but also
non-surgeons who are part of the greater cardiovascular
community. So it's tremendously important and we're very thankful
for that opportunity.


Dr. James de Lemos:


Well, I'd like to thank all our listeners for joining us today
and remind you to tune in next week when Greg and Carolyn will be
back for their regularly scheduled podcast.


Dr. Greg Hundley:


This program is copyright of the American Heart Association 2022.
The opinions expressed by speakers in this podcast are their own
and not necessarily those of the editors or of the American Heart
Association. For more, please visit ahajournals.org.