Circulation August 2, 2016, Issue

Carolyn:
Welcome to Circulation on the Run, your weekly podcast summary
and backstage pass to the journal and its editors. I'm doctor
Carolyn Lam, associate editor from the National Heart Center and
Duke National University of Singapore. Joining on me in just a
moment are two guests to discuss a very exciting new category of
papers, known as the white paper. The topic for today is an
evolution within the field of current day percutaneous coronary
intervention that of the treatment of higher risk patients with
an indication for revascularization. But first, here is your
summary of this week's journal.


 
 
The first study is from first author doctor Jolis and
corresponding author doctor Grainger, from the duke clinical
research institute in Durham, North Carolina. These authors
describe the American Heart Association Mission: Lifeline, STEMI
Systems Accelerator. This exciting project represents the largest
effort ever attempted in the United States to organize ST segment
elevation myocardial infarction care across multiple regions,
including 484 hospitals, 1,253 emergency medical services across
sixteen regions and involving more than 23,800 patients.


 
 
Indeed, this project aims to organize coordinated regional
reperfusion plans so as to increase the proportion of patients
treated within guideline goals, that is a first medical contact
to devise time of less than 90 minutes for STEMI patients
directly presenting to PCI capable hospitals and less than 120
minutes for transferred patients.


 
 
The authors observed that during the study period of July 2012 to
December 2013, there was a significant increase in the proportion
of patients meeting these guideline goals, including an increase
from 50% to 55% of STEMI patients directly presenting via
emergency services and from 44% to 48% of those transfer
patients. The authors concluded that these improvements, while
modest, suggest the potential for reductions in total ischemic
time and happily observe corresponding trends towards lower
in-hospital mortality compared with the national data towards the
end of the measurement period. Indeed, the tickle message is that
the findings support continued efforts to implement regional
STEMI networks.


 
 
The next study is by first author doctor Hidari and corresponding
author doctor Kuang from the Brigham and Women's Hospital in
Boston, Massachusetts. They describe the OMEGA-REMODEL randomized
clinical trial. This is a multi-center, double-blinded, placebo
control trial of 358 participants presenting within acute
myocardial infarction who are randomized to six months of high
dose omega-3 fatty acids at four grams daily versus placebo.


 
 
Cardiac magnetic resonance imaging was used to assess cardiac
structure and tissue characteristics at baseline and following
therapy with the primary study in point being a change in left
ventricular systolic volume index. Indeed, the authors reported
that compared to placebo, patients who received four grams daily
omega-3 fatty acids experienced significant improvements in both
left ventricular and systolic volume and surrogate measures of
non-infarct myocardial fibrosis during the six months of
treatment.


 
 
These remodeling benefits further followed a dose response
relationship with the rise in the in vivo omega-3 fatty acid
levels as quantified by your red blood cell index. They concluded
that four grams daily of omega-3 fatty acid is a safe and
effective treatment in improving cardiac remodeling in patients
receiving current guideline based post-myocardial infarction
therapies. Indeed, this does warrant perspective clinical
studies.


 
 
The third study is by first author doctor Liu and corresponding
author doctor Sia from University of Texas, Houston Medical
School and Colleagues, who sought to understand the molecular
basis underlying adaption to high altitude hypoxia. By conducting
both human high altitude and most genetic studies, the authors
identified a novel functional role of CD73-dependent elevations
in extracellular adenosin signolin in response to high altitude
hypoxia.


 
 
This led to sequential activation of a readthrough site
AMP-activated protein kinase, which in turn resulted in increased
2,3-bisphosphoglyceric production and enhanced oxygen release
capacity to peripheral tissues. Thus, reducing tissue hypoxia,
inflammation and pulmonary injury. These findings have
significantly added to our understanding of the molecular
mechanisms underlying adaption to hypoxia. Thereby, opened novel
therapeutic possibilities for the prevention and treatment of
hypoxia related conditions.


 
 
The final study is from first author doctor Yen and corresponding
author doctor Chen from the National Taiwan University and
Colleagues, who aimed to determine the effect of betel nut
chewing and paternal smoking on the risks of early metabolic
syndrome in human offspring. The author studied more than 13,000
parent-child trios identified from more than 238,000 Taiwanese
aged 20 years or older screened in two large community based
screening cohorts.


 
 
The main finding was that pre-fatherhood habits of both betel nut
chewing and cigarette smoking led to a 77% and 27% increase in
risk of early metabolic syndrome in their offspring respectively.
In fact, they even observed a dose-response relationship where
the risk was higher with an increase in duration of exposure as
well as with earlier age of starting exposure. These findings
interestingly suggest that genetic or epigenetic changes due to
exposure to both betel nut and cigarette smoking before birth can
contribute to early occurrence of metabolic syndrome in
offspring. In fact, these findings really support education for
avoidance of these habits or cessation of these habits.


 
 
That was your weekly summary. Now, for our feature paper. Our
feature paper this week is a white paper regarding the treatment
of higher risk patients with an indication for revascularization
and evolution within the field current-day percutaneous coronary
intervention. To join me in this discussion, I'll have the first
and corresponding author doctor Ajay Kirtane from Colombia
University Medical Center, New York Presbyterian hospital, as
well as doctor [Manus Brelaques 00:08:22], associate editor from
UT Southwestern. Welcome, Ajay and Manus.


 
Ajay:
Thanks so much for having us.


 
Manus:
Thanks Carolyn.


 
Carolyn:
Great. Manus, I would love if we could start by talking about the
concept of the white paper and what circulation is looking in
these white papers.


 
Manus:
Of course. It is a very exciting part of the new circulation
which is for topics that are very timely and important, but at
the same time there's not enough populous data and populous
literature to be able to address it in a more formal systematic
review way. The concept is that establish the leaders in the
field. I'm going to provide their perspectives which have derived
through their clinical practice and be able to inform us of what
the current issues are, how can they best be addressed and what
are the next steps forward.


 
Carolyn:
That's great, and what a great example to start with with this
paper by Ajay. Ajay, maybe I could just start by asking you to
make it crystal clear to us the kind of patients you're referring
to in this higher risk and the context and the scope of the
problem that you're talking about in your paper.


 
Ajay:
Absolutely. First of all, I'm honored that you would consider
that's both timely and important and that this will be one of the
new papers in the series on behalf of all the [cohorts 00:09:44]
is we're really pleased to be able to discuss it. I think the
reason that we find this really critical at this juncture is
because what we're sort of saying is an evolution in current-day
[catlab 00:09:53] practice. There are many patients now who were
seen that have either been turned down for cardiac surgery of
have highly complex disease that we know merit revascularization.


 
 
In other words, medical therapy has failed for them either from
the symptomatic standpoint or because it puts them at too high
risk given the complexity of their coronary anatomy and where
these lesions are located. Yet at the same time, in order to be
able to treat these patients effectively, we need to grasp not
only advanced techniques in terms of how to do it, but also need
to be able to select the patients appropriately so that they can
undergo these procedures safely and to drag the benefit that we'd
like to be able to offer them.


 
 
Just one brief thing to mention is that we certainly know that
over the past 10 years or so, there's been a lot of criticism of
the PCI procedures they could perform, particularly here in the
United states. Some of them were perhaps unnecessary or some of
them were not necessarily benefiting patients. The good news is
we've curtailed a lot of that, but yet at the same with that
curtail we've sort of seen a decline in these types of cases that
we refer to in the paper where patients really could benefit from
revascularization, but for whatever reason or not being offered
it.


 
Carolyn:
Listeners might be wondering though, what is the difference
between what you're talking about high risk, and we read a lot of
papers about complex procedures and complex PCI, you want to make
that differentiation just slightly clearer?


 
Ajay:
Sure. I think that complex PCI has been something that carries
the historical definition and usually involves lesion subsets
like the left main, chronic total occlusion, bifurcations, that
require more than just a simple predilatation stent implantation.
The concept of procedural risk though while it overlaps with
complexity, to some extent actually has other inputs. For
instance, the ventricular function of the patient whether or not
the other circulation is also compromised, so it's a larger
ischemic territory, and similarly some things that were
previously complex with an evolution of techniques actually don't
offer or confer that much greater risk on patients.


 
 
I would say when I did my fellowship training, left main was
something that my heart rate got up for and we were worried about
the patient in that respect. Now when we do left mains, it's
actually something where we view it as one of the more simple
things that we do relative to for instance the retrograde
approach to a CTO revascularization. There's been an evolution
and there's an overlap of what's complex and what's high risk.


 
Carolyn:
Very nicely put. Could you tell us a little bit about how your
paper is structured? I really like for example the way your
tables are laid out and so on, but maybe just give an overview?


 
Ajay:
Absolutely. I think we start off with just setting the scope of
the problem. Basically, looking at coronary heart disease and the
fact that there are subsets of coronary diseases for which has
prognosticked the importance to revascularize. For instance, the
publication of this ten-year result for the first trial
[inaudible 00:12:45] revascularization as a whole. We talk a
little bit about the assessment of procedural risk and then we
sort of move on in the end to the various areas that
interventionalists need to become better trained in order to deal
with these types of patients. I have to give credit where credit
is due. The tables that you like so much were actually the
suggestion of the editors.


 
 
Because of the new theory, Manus had a lot to do with this. I
think it's very important for people to understand, at least for
this paper the role, the back-and-forth conversation between not
only us, but also the editors and the reviewers play in bringing
this manuscript to its final form. I really give them credit for
it. What's in the tables are not only descriptions of the types
of multidisciplinary teams that are needed in order to [affect
00:13:27] that we take of these patients. Also, the techniques
that would be useful for interventionalists to know how to use
and be [inaudible 00:13:33] to take care of these patients.
Finally, a table looking at future directions because it's all
good and fine for us to say this is a new area and we're moving
into it, but we need to sort of generate the research and the
evidence base to really support the treatment that we're trying
offer or saying we can offer in the manuscript.


 
Carolyn:
Manus, you have to this describe some of this back-and-forth
conversation that went on.


 
Manus:
Ajay, I wish that every author took the comments as well as you
did because that's definitely not the case. I must admit that it
was a pleasure working with you because again you were so open to
all the comments and suggestions even though some were tough
ones. I think the interaction and being so open I think made the
paper better and we're very, very appreciative for your response
to those.


 
Ajay:
I think at the end of the day when you have a new editor team
taking over, there are going to be changes and some changes you
learn how to grow through and other changes you basically adopt
what the previous editors were doing. At least my experience, not
to [despair 00:14:29], is the prior circulation editors at all, I
actually had a great experience with them as well, but this was
novel, and I think it's something that for many authors will find
quite nice to experience because there was a lot of back and
forth. Some parts were contemptuous, but these were all resolved.
I wrote in my response back to the reviewers I really do feel the
paper was better as a result.


 
Manus:
I think that's the idea that [inaudible 00:14:51] the language
and the whole editorial team is trying to enforce and we're very
happy with it and enjoyed.


 
Carolyn:
I couldn't agree more. Actually, Manus I was also going to ask
the title is provocative. It says this is an evolution and even
in the conclusion of the paper that this could be a new field of
coronary interventional procedures. I really love your thoughts.
Is this a beginning of a whole new field?


 
Manus:
I personally do believe and many people I think do believe that
there's a tremendous evolution that is going on right now,
continue to go on in the field compared to the early days of
[inaudible 00:15:26] where we did simple angioplasty I think it
has come a long way. But I think there is gap between what can be
done right now in terms of technical possibilities, in terms of
equipment we'll have and improved patients' quality and quantity
of life.


 
 
Actually, what is being done because as you heard from Ajay, many
of those patients who could benefit do not. Within the
environment of trying to stop in a [inaudible 00:15:51]
procedure, which is very appropriate, what happened exactly is
that those more complex and high risk cases because of the fear
of complications or sub-optimal outcomes led to offering less
treatment to those complex patients.


 
 
I do believe it's an evolution in the field. I do believe that
having access to these techniques, equipment and offering options
to the patients and explaining there is benefit ratio can bring
the patient's life, make them better and bring the field forward
to the next step.


 
Carolyn:
Ajay, do you think you could elaborate a little bit more then on
what those next steps you think are and what are the future areas
of research?


 
Ajay:
Yeah, I'd certainly be happy to do so. I couldn't agree with
Manus more. I know he and I share a lot of beliefs in terms of
this. One of the things that's important to recognize is while we
can all assess procedural risk, some of these advanced techniques
are not commonly shared by all interventionalists here in the
United States, particularly if you look at the overall case
volumes of many interventionalists in the United States, there
are folks who are just not going to have the requisite volume to
be able to do complex CTO revascularization with a retrograde
approach. For instance, they would bring procedural success rates
up around 90%.


 
 
I think that some of this is education. You have to sort of
understand what can and cannot be done, what can and cannot be
done [faithfully 00:17:08] and what techniques you use or are
necessary in order to be able to improve this rate of success. If
for instance I can't do the procedure myself, then I need to be
familiar with somebody who actually can because if the patient
merits revascularization, in other words they could benefit from
having a procedure done, they're not a surgical candidate and
they could be helped by PCI, then rather than saying, "We should
just do medical therapy because I can't do the procedure." The
appropriate thing to do is to actually refer the patient to
somebody who actually could do the procedure in a safe way and
therefore ensure benefit for the patient.


 
 
That's an educational aspect. Some of it relates to training, but
I think conceptually we do need to start understanding now that
there is a sub-specialization within coronary intervention of
interventionalists who are able to offer things that many
interventionalists cannot. That's somewhat of a fundamental step
many people have to take, but I think it's time to take that step
and that was the whole point in writing this paper.


 
Carolyn:
I think that is a very effective first step that now you've
brought it to light and we're so proud and privileged to be
publishing this paper. Thank you so much Ajay, thank you so much
Manus.


 
Ajay:
Thanks so much for having us.


 
Manus:
Thanks Carolyn.


 
Carolyn:
And thank you listeners. You've been listening to Circulation on
the Run. Please tune in next week for more highlights and
discussions.