Circulation August 16, 2016 Issue

 


Carolyn:
Welcome to Circulation on the Run. Your weekly podcast summary
and backstage pass to the journal and it's editors. I'm Dr.
Carolyn Lam, associate editor from the National Heart Center and
Duke National University of Singapore. I am so pleased to be
joined this week by Dr. Judd Hollander and Dr. Deborah Diercks to
discuss a problem that all of us, as cardiologists and emergency
department physicians will recognize. This is a feature paper on
the state of the art approach to the patient presenting to the
emergency department with symptoms and signs suggestive of an
acute coronary syndrome, but first here are the highlights of
this weeks issue.


 
 
The first study is from first author's Dr. Wing and Dr. August
from Grand Valley State University in Michigan who investigated
whether social and physical neighborhood characteristics are
related to progression of sub clinical atherosclerosis measured
by coronary artery calcium. They studied this in almost six
thousand adult participants of Mesa, a multi-ethnic study of
atherosclerosis, followed over twelve years. The main result was
that increases in density of neighborhood healthy food stores
were associated with decreases in coronary artery calcium. This
was significant even after adjusting for time varying demographic
confiders, time varying behavioral risk factors and depression.


 
 
The next study from Dr. Hess and colleagues from the University
of Colorado School of Medicine characterized rates of implantable
cardioverter defibrillator or ICD counseling and ICD use among
more than twenty-one thousand potentially ICD eligible
hospitalized heart failure patients in the Get With the
Guidelines heart failure program. This study had several notable
findings. First, only twenty-two point six percent of patients
received ICD counseling. This means that up to four out of five
hospitalized heart failure patients, eligible for ICD counseling,
did not receive it. Women were counselled less often than men and
racial or ethnic minorities were counseled less frequently than
white patients.


 
 
Among counseled patients, a totally of sixty-two point six
percent of patients received an ICD or had a documented plan for
ICD placement. Women were just as likely as men to receive an
ICD, however, ICD used differences by race and ethnicity
persisted. The clinical implications of this study are that
future quality improvement initiatives should incorporate
culturally competent ICD counseling and elevating ICD counseling
to a full performance measure and publicly reporting it by sex or
race or ethnicity may need to be considered.


 
 
The next paper is from first author Dr. Resconey and
corresponding author, Dr. Catalucci and colleagues from the
Institute of Genetic and BioMedical Research in Milan, Italy.
These authors looked at the voltage dependent [inaudible
00:03:31] calcium channel which is a key mediator of interest
[inaudible 00:03:34] calcium entry associated with various
cardiovascular conditions such as hypertrophy, atrial
fibrillation, hypertension and diabetic cardio myopathy. The
author's aim to address the problem that [inaudible 00:03:47]
approaches aimed at enhancing calcium current and inotropism in
heart failure have also frequently been found to favor
arrhythmogenesis and diastolic dysfunction. Thus, limiting their
clinical use.


 
 
The novel hypothesis addressed in this study is that a peptidome
emetic therapeutic approach may overcome the arrhythmogenic
limitations of current channel activator inotropes. To test this
hypothesis, the author's used a whole host of methods to dissect
new regulatory pathways modulating the [inaudible 00:04:24] tight
calcium channel life cycle. This included yeast, two hybrid
screenings, biochemical and molecular evaluations, protein
interaction essays, fluorescence, microscopy, and structural
molecular modeling and functional studies. Having uncovered a
novel mechanism involving the [inaudible 00:04:44] tight calcium
channel, calcium beta two chaperon, the author's then generated a
mimetic peptide that specifically targets this calcium beta two
chaperon. Thereby controlling the channel assembly and density of
the plasma membrane while preserving its physiological channel
function.


 
 
Finally, they showed that delivery of this mimetic peptide into a
mouse model of diabetic cardiomyopathy restored calcium balance
and recovered cardiac function. This study is so significant
because it provides the proof of concept for the exploitation of
novel therapy based on mimetic peptide technology. Really opens
the field to mimetic peptides being used as innovative
therapeutic tools for the treatment of cardiac disease.


 
 
The last study is from Dr. Cammel from the Feil Family Brain and
Mind Research Institute in New York and colleagues who studied
the association between pregnancy and aortic complications such
as dissection or rupture. They used data on all emergency
department visits and acute care hospitalizations at nonfederal
health care facilities in California and New York between the
period of 2005 to 2013. This was a cohort crossover study where
they authors defined the period of risk as six months before
delivery until three months after delivery. Compared each
patient's likelihood of aortic complications during this high
risk period to an equivalent control period of two hundred and
seventy days exactly one year later.


 
 
Among more than six and a half million pregnancies in almost five
million women, they identify thirty-six cases of aortic
dissectional rupture during the high risk pregnancy period and
nine cases during the control period. This gives the rate of
aortic complications a five point five per million patients
during pregnancy compared to one point four per million during
the equivalent period one year later. Thus, pregnancy was
associated with a significantly increased risk of aortic
dissectional rupture with an incidence rate ratio of four
compared to the control period one year later.


 
 
Furthermore, absolute risks were particularly elevated in those
with a documented diagnosis of hypertension or a connective
tissue disease. These findings have clinical implications for the
counseling of patients at high base line risk of aortic
complications and they also further suggest that clinicians may
need to have a lower threshold for initiating diagnostic testing
for symptoms of a possible aortic dissection or rupture in
pregnant or postpartum patients and especially in those with
connective tissue disorders or hypertension.


 
 
Our feature paper this week discusses a problem that impacts
twenty million patients in North America and Europe every year.
What am I talking about? These are patients presenting to the
emergency department with symptoms and signs suggestive of an
acute coronary syndrome. Who am I talking with? Well, today we
have first author Dr. Judd Hollander from Thomas Jefferson
University and Dr. Deborah Diercks associate editor from UT
Southwestern. Welcome Judd and Deborah.


 
Dr. Deborah:
Thank you.


 
Dr. Judd:
Thank you.


 
Carolyn:
Let's start with a behind the scenes look at this paper. It's an
in depth review that was invited by the editorial team. Deborah,
can you tell us how this idea came about?


 
Dr. Deborah:
I think one of the goals of the editorial board of circulation is
really to provide great clinical reviews that really could
benefit the members. I have a unique aspect in that I'm an
emergency physician. This idea was really brought about by
discussion of really what can we merge cardiology and emergency
medicine with. What would be the most clinically issue we're
challenged with right now? You can't get two emergency physicians
in a cardiologist's room together without some discussion and
challenge around the [inaudible 00:09:11].


 
 
There's been so many changes in the last decade and so much more
information about how we can use these in a clinically relevant
way. It really fit nicely into a really great review article and
I am really happy that we are able to invite Judd who's well
known to the US and one of the leaders in the United States in
this area and also an international group inviting a cardiologist
from Europe and also an emergency physician from New Zealand to
participate in it.


 
Carolyn:
Judd, what is the take home message of this in depth review from
your point of view?


 
Dr. Judd:
I think the biggest take home message is we have known for
decades and decades that if we rely on our clinical judgement we
miss too many patients. We send home people that will be having
acute coronary syndromes and acute myocardial infraction and the
challenge over the last decades of trying to find ways where
we're not going to spend a ton of money over admitting people to
the hospital because of a fear of missing an event that may
happen five percent of the time.


 
 
The beauty of the advances in troponins is we now have troponins
that now have increasing sensitivity whether they be the non high
sensitivity troponins used in the US or the high sensitivity
troponins that are actually used in Europe and the rest of the
world. We can use those better [inaudible 00:10:29] and combine
them with clinical decision rules to create accelerated
diagnostic pathways which is a big term. For now, if we put a
blood test together with a structured clinical decision rule, we
can, with more than ninety-nine percent negative predictor value,
find patients who are safe to send home.


 
Carolyn:
Judd, I really have to congratulate you on such a beautiful
paper. You really did cover all of that but what I love most is
the way that you've managed to summarize very clearly a whole
wealth of information because when you talk about biomarkers,
there's so many out there and there's zero hour, one hour, two
hours, this score and that score. I'm actually looking at table
one now where you show a summary of the biomarkers strategies and
then, in table two, you show a summary of the risk scores and
then the performance measures of each of these scores. That must
have taken quite a lot to put together.


 
Dr. Judd:
I think that's why Deb was very smart and invited authors from
around the world. We have Christian Muller from Switzerland and
Martin Tann from New Zealand which, literally, means we're all on
different time zones and we were able to work around the clock to
do that. There as always somebody awake. Getting more series, the
nice thing is that my colleagues on this paper are some of the
leaders in doing this kind of research. In fact, they are the
leaders in doing this kind of research.


 
 
What I think is very challenging for the average cardiologist or
the average emergency physician is there have been so many
different approaches and many of them actually work. The
challenge for us was to try and make it relatively simple so you
can choose the approach at your institution and put it into a
structured pathway and pick the one that works best for you. You
can get a ninety-nine percent negative predicted value using the
right essays with samples that the time of presentation and one
hour later, you can get a ninety-nine percent negative predictor
value at zero and two hours. You can combine it with an
accelerated diagnostic pathway and do that at zero and two hours
and zero and three hours.


 
 
I think the important thing is you need to figure out what will
your clinicians use? Certain clinicians may be very comfortable
with one risk score and not another and then they need to combine
the timing of testing with the risk score their comfortable with
in order for us to achieve the great possibilities we have with
these new tasks. I think when you try and do a one size fits all,
there are going to be people who push back because they don't
like one component of the risk score. Really what we're trying to
do and we didn't say everybody should do A, B or C but we present
the data on five or six different options and let people choose
what is most feasible for them.


 
Carolyn:
How wonderful. Deborah, what were you thinking when you were
reviewing this paper and trying to structure it for the clinician
out there who wants to use this information?


 
Dr. Deborah:
I think that, overall, we were really impressed by the clarity
and the ease that a reader can take this information home. There
is so much information out there and there are so many different
ways to apply it that we're really impressed how the authors put
it in a really pretty clear manner so you can actually see the
risk stratification tools that are out there, what they're used
with and what type of troponins. Think about your own clinical
practice and what you can adapt really based on the evidence that
is out there.


 
Carolyn:
I couldn't agree more. Judd, how about this issue of the coronary
CT angiogram and where that falls?


 
Dr. Judd:
That's really an interesting question because there's been a lot
of publicity and a lot of editorializing in recent years that
maybe you can make a decision with your two troponins and your
biomarkers and decrease the number of people that need downstream
testing. One of the dilemma with this, like I said before, is we
know we're not really good at predicting who has acute coronary
syndrome based on clinical things and for that reason the
European Society guidelines as well as the American AHAACC
guidelines have always said you need to do two things. You need
to rule out acute myocardial infraction and you need to risk
stratify patients for underlying coronary disease. When a patient
comes into the emergency department, if I'm going to be guideline
compliant with the recommendations in the world, I need to do
both things.


 
 
The paper, we summarize really clearly ways you can get out of
the woods with biomarket testing and clinical pathways but then
you still want to risk strategy for coronary disease. There are
sometimes where you might not need that downstream testing but
what coronary CTA really lets us do is it makes us more efficient
than a stress test. A stress test I like to say is a next day
test; although there is data that you can do it when the
patient's in the emergency department rapidly. It certainly is
not the standard practice.


 
 
There are people afraid of putting people on the treadmill too
soon in case they have unstable angina but a coronary CTA lets me
look at the coronary arteries, immediately, when they're in the
emergency department. There's very few areas in emergency
medicine where there are three large randomized control trials
that all give the same results. It doesn't say coronary CTA is
better than a next day stress test but it does say you can avoid
admission and, hence, save some dollars. It says you can send
patients home sooner and, hence, save some angst that the
patients may feel while they're in that diagnostic indecision
area.


 
Carolyn:
That's such a practical summary and, in fact, it really reflects
the entire paper which is really so clearly presenting the
information. Judd, one last thing, could I check is this correct,
in my understanding, that the main difference between this and
say the guidelines that you just measured is that what you do
here is really give the readers all the information? As you say,
allow the readers to choose what suits them best. This is not
making recommendations, it's summarizing all the information. Is
that right?


 
Dr. Judd:
Yeah, that's exactly right. If you look, I think it's table
number four, where we go through each one of the decision aids
and how many or what percent of patients actually fit into that
decision aid and what the negative predictive value is for that
decision aid combined with troponin. Then what type of troponin
was used to achieve those results, you'll see that about half the
studies are done with, what we call, the contemporary troponin or
just the regular sensitivity troponin that we use in the United
States. The other half of the data we show is with high
sensitivity troponins. It would not be a good idea for somebody
creating their quality program in their emergency department to
take something that was tested with a high sensitivity troponin
and validate it there and then apply it in an emergency
department in the United States where we don't have those
[inaudible 00:17:18].


 
 
We thought it was critically important to lay out the data and as
the high sensitivity troponins come on the market, hopefully in
the next year in the US, people can begin with something now and
switch to something else later if they want. If we made a
recommendation that was firm, the world changes too fast. I don't
think we would be doing the best for our patients.


 
Carolyn:
That is such a great statement to end this on. Thank you so much
Judd and Deborah. This was an excellent discussion.


 
Dr. Judd:
Thank you.


 
Dr. Deborah:
Thank you.


 
Carolyn:
You've been listening to Circulation on the Run. Thank you for
joining us this week and don't forget to tune in next week for
more exciting cardiology needs from all over the world.