Aug 15, 2016
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.