Aug 1, 2016
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.