Circulation May 8, 2017 Issue

Dr. Carolyn
Lam:              
Welcome to Circulation on the Run, your weekly podcast summary
and backstage pass to the journal and its editors. I'm Dr.
Carolyn Lam, Associate Editor from the National Heart Center, and
Duke National University of Singapore. In just a moment, we will
be discussing the sources of sodium in the US diet, results that
may surprise you, and that carry profound public health
importance. But first, here's your summary of this week's issue.


                                               
The first original paper advances the field of cardiac tissue
engineering by establishing a defined serum-free protocol to
generate functional human myocardium from pluripotent stem cells.
In this paper by first author, Dr. Tiburcy, corresponding author
Dr. Zimmermann and colleagues from the University Medical Center
Goettingen in Germany, the authors systematically investigated
cell composition, matrix and media conditions to generate
engineered human myocardium from embryonic and induced
pluripotent stem cells and fiberglass, under serum-free
conditions. The engineered human myocardium demonstrated
important structural and functional properties of post-natal
myocardium, including rod-shaped cardiomyocytes with M-bands,
systolic twitch forces, a positive force-frequency response,
inotropic responses to beta adrenergic stimulation, evidence of
advanced molecular maturation by transcriptome profiling and the
engineered human myocardium even responded to chronic
cholinomimetic toxicity with contractile dysfunction,
cardiomyocyte hypertrophy, cardiomyocyte death, and anti-pro BNP
release, which are all classical hallmarks of heart failure.


                                               
Finally, the authors demonstrated scalability of engineered human
myocardium according to anticipated clinical demands for cardiac
repair. In summary, this paper provides proof of concept for a
universally applicable technology for maturation and scalable
production of engineered human myocardium, something that is
termed a stride forward in an accompanying editorial by Doctors
Yang and Murray, from University of Washington in Seattle.


                                               
The next paper describes a new frontier for interventional
cardiology, the percutaneous therapy for tricuspid regurgitation.
Here, Dr. Nickenig and colleagues, from University Hospital Bonn
in Germany, recruited 64 consecutive patients deemed unsuitable
for surgery who underwent mitroclip treatment for chronic, severe
tricuspid regurgitation for compassionate use. Twenty-two
patients were also concurrently treated with a mitroclip system
for mitral regurgitation as a combined procedure. The degree of
tricuspid regurgitation was severe or massive in 88% of patients
before the procedure. The mitroclip device was successfully
implanted in the tricuspid valve in 97% of cases.


                                               
After the procedure, tricuspid regurgitation was reduced by at
least one grade in 91% of patients. 13% of patients with
tricuspid regurgitation remained severe after the procedure.
There were significant reductions in effective regurgitant
orifice area, vena contracta width, and regurgitant volume. There
were no intra-procedural deaths, cardiac tamponade, emergency
surgeries, stroke, myocardial infarction or major vascular
complications.


                                               
There were three in-hospital deaths. New York Heart Association
class was significantly improved and six minute walk distance
increased significantly. In summary, this study demonstrates that
trans-catheter treatment of tricuspid regurgitation with the
mitroclip system seems to be safe and feasible in this cohort of
pre-selected patients.


                                               
The next paper describes the pooled safety analysis of
evolocumab, a fully human monoclonal antibody to PSK-9. Dr. Toth
of Johns Hopkins University School of Medicine and the PROFICIO
investigators perform this pooled analysis from the PROFICIO
program, which included over 6,000 patients from 12 Phase 2 and 3
trials, and the corresponding open-label extension trials, and
they showed that treatment with evolocumab, up to one year, was
not associated with discernible differences in adverse events,
serious adverse events, or key laboratory assessments, compared
to control or standard of care.


                                               
In addition, adverse events rates did not increase among patients
attaining very low levels of LDL cholesterol, of less than 25
milligrams per deciliter, compared to patients attaining LDL
cholesterol levels above 40 milligrams per deciliter. In summary,
the present analysis confirms a favorable benefit risk profile
for evolocumab treatment for up to one year.


                                               
Does aggressive blood pressure lowering prevent recurrent atrial
fibrillation after catheter ablation? Well, this question is
addressed in a randomized, open-label clinical trial known as the
Substrate Modification With Aggressive Blood Pressure Control or
SMAC-AF Trial. In this trial, Dr. Parkash of Halifax, Canada and
colleagues, randomly assigned 184 patients with atrial
fibrillation and a blood pressure of greater than 130 over 80 to
aggressive blood pressure lowering, with a target of less than
120 over 80, or to standard blood pressure treatment, to a target
of less 140 over 90, prior to their scheduled atrial fibrillation
catheter ablation.


                                               
The primary outcome was symptomatic recurrence of atrial
fibrillation, atrial tachycardia, or atrial flutter lasting
greater than 30 seconds, determined 3 months beyond catheter
ablation. The authors found no additional benefit to the addition
of aggressive blood pressure lowering over a median of 3.5
months, over standard blood pressure therapy, in patients
undergoing catheter ablation for atrial fibrillation to prevent
recurring atrial arrhythmia.


                                               
In subgroup analysis, a signal of benefit was observed in groups
whose blood pressure were lower at the point of entry into the
study, and in those patients who were older. The duration of
blood pressure lowering in the study did not result in reduction
of recurrent atrial fibrillation after catheter ablation, however
there was a higher rate of hypotension requiring medication
adjustment in the aggressive blood pressure group.


                                               
Thus, this trial showed that neither aggressive blood pressure
lowering compared to standard blood pressure lowering, nor the
duration of aggressive blood pressure treatment reduced atrial
arrhythmia occurrence after catheter ablation for atrial
fibrillation, but resulted in more hypotension.


                                               
Well, that wraps it up for our summaries! Now, for our feature
discussion ...


                                               
Our topic today is so universal and so important. It's about
sodium intake and the sources of sodium, at least in the US, and
I have with me two lovely ladies, the corresponding author of our
paper, Dr. Lisa Harnack, from School of Public Health, University
of Minnesota, and a regular on the show, shall I say, Dr. Wendy
Post, Associate Editor from Johns Hopkins. Welcome, ladies!


Dr. Wendy
Post:              
Thanks you, Carolyn! It's a pleasure to be here.


Dr. Lisa
Harnack:              
Thanks, thanks.


Dr. Carolyn
Lam:              
Lisa, let's dig right into your paper. Let's start by discussing
that there was a prior paper that looked at sources of sodium in
the US population. So please tell us, what inspired you to do
your paper, and were you surprised by your findings?


Dr. Lisa
Harnack:              
Right, well the previous study was over 25 years old, and it
involved just 69 people from one geographic area, and, you know,
it was informative, but it didn't tell us about America today,
and how much sodium we're getting from different sources, and it
didn't tell us much about a variety of ethnic groups ... we're a
diverse country. So the CDC actually funded this study, and
really they saw the need for it and laid out that this study
needed to be done, as it was done, in three geographic areas,
representing different ethnic groups.


Dr. Carolyn
Lam:              
Tell us what you did.


Dr. Lisa
Harnack:              
So, we recruited 450 people from 3 different areas, from
Minneapolis/St. Paul metropolitan area ... Stanford was a partner
in this study and they recruited people from that area of
California, and then, finally, Birmingham, Alabama was a partner
was a partner, and we got participants from there.


                                               
So the racial groups we had represented were white Americans,
African Americans, Asian Americans and Hispanics.


Dr. Carolyn
Lam:              
Yeah, I was really struck ... you had almost equal representation
of women as well, didn't you?


Dr. Lisa
Harnack:              
Right, so we made sure we had half of the participants were
women, so we could really see how things stood with a variety of
groups.


Dr. Carolyn
Lam:              
That's excellent. What I was really impressed, as I'm sure,
Wendy, you were, too, was the detail of the methodology. Could
you tell us a little bit about that?


Dr. Wendy
Post:              
Right, so we wanted to know all the sources of sodium. Part
studies have tended to not ask about salt added to food at the
table, and in home food preparation, because it's really hard to
actually know ... you know, if you ask somebody, "Oh, did you add
salt at the table? How much did you add?" They don't know. They
just say, "Oh, well, I shook some salt on." So, we had people
collect duplicate samples of the salt they added to food at the
table and home food preparation. We gave them little baggies ...
collection bags ... you know, after they added salt at the table,
shake some into the baggy. So, we knew exactly how much because
people do add salt in the home, so they have some control over
how much sodium is in their diet. But the question is in how much
under people's control in their home versus what's coming from
the food supply.


Dr. Carolyn
Lam:              
Right. And what I loved about the results is ... I think that it
would challenge a lot of what people expect. Because when we talk
about sodium restriction, everyone thinks, "Oh, it's the
additional salt we add." And your study actually had surprising
results. So, could you tell us?


Dr. Wendy
Post:              
Yes, so it really was clear that the salt that people add at the
table is just 5% of their total sodium intake, on average, across
people in our study, and the salt added in home food preparation,
like maybe the salt you add to your pasta when you're boiling it
or to your eggs ... that was just 6%. So, 11% of the sodium in
our study participants' diets was sort of that under-your-control
in-the-home, and the rest was from other sources. So, the other
things we looked at was, "Will water contribute some sodium?" So,
we wanted to see how much comes from your home tap water. There's
sodium that's just naturally occurring in food, like milk just
naturally contains some sodium. So we wanted to look and see how
much came from just naturally occurring in the food, and then the
other question was how much is added by food manufacturers as
part of making the food product, and that included the salt that
might be added in making potato chips, as well as in restaurants
... the salt that might be added in making French fries or a
pasta dish at a restaurant.


Dr. Carolyn
Lam:              
And the biggest culprit?


Dr. Lisa
Harnack:              
Yes, the biggest culprit was that latter source ... food added in
processing.


Dr. Carolyn
Lam:              
I thought that was amazing. Wendy, what do you think the public
health message is? I mean, 70% almost of the salt's coming from
processed foods from outside. What do we do? Stop eating it? What
do we do?


Dr. Wendy
Post:              
Right, so, on the editorial board for Circulation, we really
liked this paper because of its very high impact for a public
health message. So, as was stated, the sodium that we're getting
in our diet is largely coming from processed foods and from foods
we eat in a restaurant. So there are a number of ways that that
can be modified and one is for our patients to read food labels
and to make smart choices when they are shopping for processed
foods in the supermarket.


                                               
But the other is for food manufacturers to decrease the amount of
sodium in the products that they are making and there are
voluntary suggestions by the FDA that food manufacturers reduce
the sodium content of the food, and especially bread is
incredibly high in sodium, and I suspect that most of our
patients don't know that. So, if we were able to reduce the
amount of sodium in the food supply by just a small fraction, it
could have a large public health impact because we all eat.


                                               
So, it would affect everybody, and then I think the other really
important public health message is about eating in restaurants
and, of course, some people eat out more than others, and some
people eat out in fast food restaurants, which, of course, are
very high in sodium, but even in some of the nice restaurants
that we go to, even expensive restaurants, the food is very
heavily salted and I, for one, when I go out to eat, and
sometimes don't like the taste of the food because it has so much
salt in it, when I'm used to eating a low sodium diet.


                                               
So, there are a number of changes that occur on that level. One
is for our patients to understand what foods tend to have a lot
of sodium at a restaurant, but also for restaurants to notify
their clientele of what foods are potentially lower in sodium and
calories and generally provide the nutrient value so that we can
make smart choices when we eat out.


Dr. Carolyn
Lam:              
Yeah, indeed, congratulations, Lisa - what an important paper.
Quick question, so that was the overall main message, but did you
find any differences by different racial groups, by sex, by
different socioeconomic status?


Dr. Lisa
Harnack:              
We did find some differences. We found one difference was it
looked like African Americans tend to add more salt at the table
than some of the other groups, and, actually, Asians add less in
our study. But still for all groups, that sodium added to food in
processing was still the main source by a long shot, so, although
there were some small differences by groups, it was clear that
for all groups, the issue was the sodium added in processing.


Dr. Carolyn
Lam:              
And for both Lisa and for Wendy, do you think these results are
generalizable even beyond the US?


Dr. Wendy
Post:              
I'd imagine that there would be quite a lot of variability, based
on the habits of the various populations. So, here we're talking
about eating outside the home, or food that's processed outside
of the home, so there may be countries where most people are
producing their own food and not necessarily buying processed
foods or eating in restaurants, and then this would definitely be
less applicable. And, of course, there are differences in foods
that we eat based on our different ethnic groups.


Dr. Lisa
Harnack:              
No, I would agree with what's just said. It really could be
variable, but it does seem that a lot of countries are concerned
about processed foods. Some countries implemented mandatory
limits on the sodium in the foods in their food supply, so that
would indicate to me that they know there's ... for some
countries, there's serious concern about this source of sodium.


Dr. Carolyn
Lam:              
Yeah, and I think this is really a wake-up message for us to
examine where these sources of sodium ... I mean, even that
simple message that it could be coming from bread, from drinking
water, I think that would be surprising to a lot of us, even
those of us practicing in medicine. Wendy, finally, you thought
this was important enough to invite an editorial. I'd really like
your thoughts there.


Dr. Wendy
Post:              
You'll be able to read the editorial when it comes out in print,
but the editorial also congratulates the authors on a really
important paper, and the important public health messages, and,
especially, compliments the authors on having a diverse group of
participants, including ethnic minorities and men and women, and
different geographic locations, so overall, it's a very important
paper that I'm sure will have an important impact on the public
health of our country and others.


Dr. Carolyn
Lam:              
Listeners, you heard it right here. Remember, you're listening to
Circulation on the Run. Please share this episode, and tune again
next week!