Jul 2, 2018
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. This week features
Circulation Global Rounds, a brand-new series of papers from all
across the world that you are going to want to hear about, coming
right up after these summaries.
The first original paper this week tells us that community trends
and acute decompensated heart failure may differ by race and sex.
Dr Patricia Chang from University of North Carolina in Chapel Hill
and colleagues examine the 10-year rates and trends of hospitalized
acute decompensated heart failure in the Atherosclerosis Risk in
Communities or ARIC study, which sampled heart failure–related
hospitalizations in four US communities from 2005 to 2014, using
ICD-9 codes. They found that acute heart failure with reduced
ejection fraction was more common in black men and white men,
whereas acute heart failure with preserved ejection fraction was
most common in white women.
Rates of hospitalized acute decompensated heart failure increased
over time, with higher rates in blacks, and rising cases of
preserved ejection fraction heart failure. Mortality rates were 30%
at one year with a more pronounced decrease over time in blacks but
generally did not differ by heart failure types. Whether racial
differences may be related to age of onset comorbidities, or other
community level and social economic factors, deserve further
study.
The next paper is a population-based study identifying long-term
outcomes and risk factors and children with hypertrophic
cardiomyopathy. Dr Alexander from Boston Children's Hospital and
colleagues examine the National Australian Childhood Cardiomyopathy
Study, a long-term national cohort study with a median follow-up
duration of 15 years. They found that the greatest risk of death or
transplantation for children with hypertrophic cardiomyopathy was
in the first year after diagnosis, with 14% of patients achieving
this combined end point compared to 0.4% per year thereafter.
Risk factors for death or transplantation included symmetric left
ventricular hypertrophy at diagnosis, Noonan syndrome, increasing
left ventricular free wall thickness, and lower fractional
shortening during follow up. The majority of surviving patients had
no symptoms. Thus, children with hypertrophic cardiomyopathy who
are alive one year after diagnosis have a low long-term rate of
death or transplantation. Deaths from heart failure usually occur
soon after diagnosis, whereas the risk of sudden cardiac death is
ongoing.
The next paper is the first demonstration of a peripheral clock in
the perivascular adipose tissue that could contribute to the
homeostatic regulation of circadian blood pressure variation.
Co-corresponding authors Dr Chang and Chen from University of
Michigan and their colleagues used a novel brown adipose specific
aryl hydrocarbon receptor, nuclear translocator-like protein 1 or
Bmal1 and angiotensinogen knockout mouse model to demonstrate that
local Bmal1 in perivascular adipose tissue regulated
angiotensinogen expression
and the ensuing increase in angiotensin II, which acted on smooth
muscle cells
in the vessel walls to regulate basal activity and blood pressure
in a circadian
fashion during the resting phase. In fact, deletion of Bmal1 or
angiotensinogen
in the perivascular adipose tissue resulted in a superdipper
phenotype with
exacerbated hypotension during the resting phase. These findings
imply that it
is possible that obesity could alter the perivascular adipose
tissue peripheral
clock, thus promoting abnormal dipper phenotypes and increasing
cardiovascular risk. The results therefore inform the design of
novel therapeutic
approaches for hypertension by targeting the perivascular adipose
tissue
peripheral clock.
What is the net clinical benefit of oral anticoagulation for very
elderly patients
with atrial fibrillation? Well, the next paper by first author Dr
Chao, cocorresponding
authors, Dr Chen from Taipei Veterans General Hospital and Dr
Lip from University of Birmingham, addresses this question. These
authors use a
nationwide cohorts study in Taiwan to compare the risks of ischemic
stroke and
intercerebral hemorrhage between patients with and without atrial
fibrillation,
all aged 90 years and above, from 1996 to 2011, and they also
compared
patients treated with warfarin and non-vitamin K antagonists
oral
anticoagulants, or NOX from 2012 to 2015 when NOX were available in
Taiwan.
They found that even among these very elderly patients aged 90
years and
above, atrial fibrillation was associated with an increased risk of
ischemic stroke
compared to patients without atrial fibrillation. Warfarin use was
associated
with a lower risk of ischemic stroke, with no difference in
intercerebral
hemorrhage risk compared to nonwarfarin treatment. The use of
warfarin was
associated with a positive net clinical benefit compared to being
untreated or to
antiplatelet therapy. Compared to warfarin, NOX were associated
with a lower
risk of intracerebral hemorrhage, with no difference in the risk of
ischemic
stroke. Thus, oral anticoagulation may still be considered for
thromboprophylaxis in very elderly patients with atrial
fibrillation, with NOX
being a favorable choice
The final paper provides insights into the mechanisms linking
obesity and
cardiovascular diseases. Co-corresponding authors, Dr Kong and Wang
from
Peking University Health Science Center and colleagues use a
combination of
animal models and human adipose biopsies to characterize a new
adipokine
named family with sequence similarity 19, member A5 or FAM19A5.
This novel
adipokine was capable of inhibiting post injury neointoma
information via
sphingosine-1-phosphate receptor 2 and downstream G12/13-RhoA
signaling.
Thus, down regulation of FAM19A5 during obesity and loss of its
vascular
protective function may trigger cardiometabolic diseases.
Well, that wraps it up for our summaries. Now for our feature
discussion.
I'm just so excited about today's feature discussion, because we're
talking about
Circulation going global. And I am just absolutely delighted to
have with us, our
Editor-in-Chief himself, Dr Joe Hill from UT Southwestern, as well
as our Senior
Advisory Editor, Dr Paul Armstrong from University of Alberta. So
Joe, could you
start by telling us a little bit more about your vision for the
global outreach of
Circulation?
Dr Joe Hill: Thank you, Carolyn. As I hope our readers are aware,
Circulation is a global
journal with a global footprint. We have editors distributed around
the world in
16 countries and 10 time zones. And importantly, those editors all
have an
equivalent role at the leadership table. Part of the reason for
this is because
cardiovascular disease is now, as we are all aware, a global
scourge. There are
no more final frontiers for cardiovascular disease. That said, the
manifestations
of cardiovascular disease differ in different parts of the world.
In the developed
world, and the developing world, for example, the way
cardiovascular disease
manifests itself can be very different. And at the same time, the
way in which
the disorders are tackled are different. The way we tackle heart
disease in the
West can be different than it is in the East, for example. And
there are
important initiatives that have emerged in different pockets of the
world, best
practices that we need to understand better. What can we all learn
from the
way in which cardiovascular disease manifests itself around the
world and it's
being addressed around the world?
Dr Carolyn Lam: Joe, you had me at hello. I remember that when you
first took over as Editor-in -
Chief and I heard you say this, I was just floored, because coming
from
Singapore and all our listeners out there in Japan and China, we
just really
appreciate that global outlook. So thank you, on behalf of us all.
Tell us a bit
more about this new initiative then for the journal.
Dr Joe Hill: I will tell you in broad strokes, that Paul Armstrong,
a noted clinical trial is from
Canada, who is a household name in the cardiovascular world, he and
I cooked
up a scheme that Paul will describe, where we will reach out on a
regular basis
for insights from various different countries, ultimately, circling
the globe
progressively over time. And I will defer to Paul to tell us more
about the
specifics.
Dr Paul Armstrong: Carolyn, it's an exciting initiative and as
someone a little long in the tooth, but
still believing that you can teach an old dog new tricks, I would
point out that
Circulation is almost 70 years old, and it has staying power. And
one of the
reasons that it has staying power is because it is capable of
reinventing itself,
and so I was attracted to help out again, from the editorial
process, given Joe's
vision and leadership and the excitement around the reinvention
that you've
described, to get involved with this initiative. And I was
inspired, of course, by
the fact that those of us who do clinical trials appreciate that a
lot of different
ideas, a lot of different cultures and perspectives are brought to
a collaborative
table. And I'm thinking back now, Carolyn to three years ago, when
you and I
first met enjoying courses as part of a trial in heart failure,
which involves 43
countries, 800 sites, it will be 5000 patients centers, we've
traveled separately
and together around the world, convincing people that there are
unmet needs
in heart failure and other parts of cardiovascular disease, we
learned that the
approach to standard of care, the rigor which is applied, the
exquisite
sensitivities around differences that are meaningful, and the
tricks that some
investigators and countries use that we can all I think, learn from
has been very
revealing.
So I think in this initiative, we want to have thought leaders. And
we've already I
think, commenced and have two outstanding leaders from Japan and
India to
come forward in the first two quarters of this initiative. Tell us
about the
regional epidemiologic features, cardiovascular disease in their
regions, what
the most important challenges are, what their best practices are,
that you're
alluded to, who provides cardiovascular care and what the
impediments are to
progressing because we think if we listen and learn as essentially
knowledge
brokers, because welcome to Circulation, we can facilitate raising
the level of all
of the boats in the water and potentially make new partnerships and
do a better
job. So I'm excited about this. I'm delighted that Joe was
receptive and really
look forward to working with him and some of these terrific people
around the
world, you included who brings such a unique and important
perspective from
which we can all learn.
Dr Carolyn Lam: Oh, I love that so much Paul. Thanks for putting it
that way. International
knowledge brokers, that's what we hope to be. Isn't that fabulous,
just an
opportunity to learn from each other, everybody having stuff to
bring to the
table? Tell us a bit more though, what are you looking for in these
papers?
Dr Paul Armstrong: We have some guidelines. But as Joe insists
we're not going to be formulaic.
We're going to allow diversity of approaches. We're going to invite
a thought
leader and hope that that thought leader might invite one or two
others, we
want to limit it to three co-authors. We want obviously some
insights into how
cardiovascular health professionals are being trained, what
research
infrastructure exists, and how they access the literature, how do
they read
Circulation, how do they read other journals, and are there
collaborative ideas
that they've developed to their neighbors to the East and West that
may be
could be broadened? Are there unmet needs that they've indicated
similar or
different from those in Western Europe, South America? We've got
about seven
or eight points of light that we hope to illuminate in the course
of this exercise.
And the prospectus that's laid out in an editorial that Joe and I
collaborated on
that I believe, Joe, is going to come out in early July.
Dr Joe Hill: That's exactly right, Paul. And I would just echo
exactly what you said that just
the opposite of a formulaic, cookie cutter approach. We want to
leverage the
beautiful diversity of our world. The different approaches that
people take to
attack this scourge that is keeping a humble approach to tackle
instead of the
visas that is humbling bar none. There is nothing that is more
globally important
than the continued growth and expansion of cardiovascular disease.
And
importantly, we can all learn from each other. There are exciting
initiatives that
I've learned about in South America and in pockets of Europe and in
Asia, and in
the Middle East that we can all benefit from, and we want to shine
a bright light
on that. These pieces will be relatively short. They will be in our
Frame of
Reference section, so 1200 words or so, so that they are accessible
so that
people, you know, feel that they can carve out, you know, four
minutes in their
busy day to read what cardiovascular disease looks like, as Paul
said, our first
ones will be from Japan and India, and we plan to reach out to
South America
and to the Middle East, and just continue on around until over the
course of the
next number of years, we've touched virtually every country in the
world.
Dr Carolyn Lam: And that's huge. And are there any specific types
of cardiovascular disease that
you might be looking to focus on?
Dr Joe Hill: You know, I don't think so. One of the points that I
have made and learned is
that in the West, in the developed world, cardiovascular disease
increasingly has
become a chronic disorder where more and more people, over the
course of the
last six years are surviving their acute coronary syndrome, their
tachyarrhythmia
events, and they are developing chronic disorders like heart
failure, whereas in
the East, it is the atherothrombotic manifestations that have both
MI and stroke
that are expanding rapidly. So given that the face of
cardiovascular disease is
different in different parts of the world, different strategies
have to be
leveraged to address that, and we want to learn about that.
Dr Carolyn Lam: I would love to have you both come talk again, when
we receive some of these
papers and just reflect on the things that we're learning. Paul,
did you have
anything else that you wanted to add?
Dr Paul Armstrong: I think, Carolyn that hits the high spots. I
suppose we should mention diabetes
and obesity and the expanding epidemic that seems to effect some
regions such
as India, in the Middle East, even more than other areas, but I
think this is going
to be great. We're gonna have some fun and learn and exciting and
hopefully it
will catalyze better care and better thinking around this enemy
that we all face.
Dr Carolyn Lam: Listeners. You heard it right here, Circulation on
the Run. I'm sure you're excited
as I am about this. You have to read the editorial. It's a
fantastic read.
Thanks for joining us today. And don't forget to tune in again next
week.