Circulation March 21, 2017 Issue

Dr.
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 this week's issue, we
are discussing if public placement of defibrillators in the
community can be improved. First, here's your summary of this
week's Journal.


                                               
Stroke incidents, prevalence, and risk factors have been changing
over the past 50 years so do we need a more contemporaneous
revised Framingham Stroke Risk profile to reflect these trends?
Well the first paper in our issue looks at this and this is from
first author Dr. Dufouil, corresponding author Dr. Seshadri and
colleagues from the Boston University School of Medicine.


                                               
Let's first recall that the Framingham Stroke Risk profile was
originally described in 1991 and integrates the effect of age,
sex, and baseline measurements of various vascular risk factors
such as systolic blood pressure, use of anti-hypertensive
medications, left ventricular hypertrophy on ECG, prevalent
cardiovascular disease, current smoking status, atrial
fibrillation and diabetes all to describe the 10-year probability
of incident stroke.


                                               
In the current paper, the authors updated the Framingham Stroke
Risk profile using the means of risk factors that reflect current
prevalence, the estimate of incident stroke to reflect current
rates, and the hazards ratio that reflect current associations.
They used the same risk factors identified in the original stroke
risk profile with the exception of left ventricular hypertrophy.
The authors compared the accuracy of the standard old risk
profile with the revised new risk profile in predicting the risk
of [alt 00:01:58] and ischemic stroke and validated the new risk
profile in two external cohorts, the three cities and regards or
reasons for geographic and ethnic differences in stroke studies.


                                               
They found that the new stroke risk profile was a better
predictor of current stroke risks in all three samples than the
original old Framingham Stroke Risk profile. The new stroke risk
profile was also a better predictor among whites compared to
blacks in the regard study. The authors therefore concluded that
a more contemporaneous revised Framingham Stroke Risk profile
could serve as the basis for examining geographic and racial
differences in stroke risk and the incremental diagnostic utility
of novel stroke risk factors.


                                               
The next study provides preclinical proof of principle that an
apelin receptor agonist may be of therapeutic use in pulmonary
arterial hypertension. And the agonist in this case is 
Elabela/Toddler or ELA, first identified as an essential peptide
in the development of the heart in Zebrafish, and subsequently
proposed as a second endogenous ligand at the G-protien coupled
apelin receptor, which works at this receptor despite a lack of
sequence similarity to the established ligand, apelin.


                                               
In this study from first author Dr. Yang, corresponding author
Dr. Davenport and colleagues  from University of Cambridge
in the United Kingdom, ELA competed for binding of apelin in
human hearts with overlap of the two peptides indicated by
encyclical modeling. ELA activated G-protein and β-arrestin
dependent pathways and as expression was detectable in human
vascular endothelium and plasma. Comparable to apelin, ELA
increased cardiac contractility, ejection fraction, cardiac
output, and elicited vasodilatation in rats in vivo. 


                                               
ELA expression was reduced in cardiopulmonary tissues from
patients with pulmonary arterial hypertension and in rat models.
Finally, ELA treatment significantly attenuated the elevation of
right ventricular systolic pressure, right ventricular
hypertrophy, and pulmonary vascular remodeling in monocrotaline
exposed rats. Thus, these results suggest that a selective
agonist that mimics the action of indulgence ligand apelin or
Elabela/Toddler, ELA, may be a promising therapeutic strategy in
the treatment of pulmonary arterial hypertension.


                                               
The final paper looks at sudden cardiac death after coronary
artery bypass grafting, its incidents, timing, and clinical
predictors. First author Dr. Rao, corresponding author Dr.
Velazquez and colleagues from Duke Clinical Research Institute in
Durham, North Carolina, looked at the patients enrolled in the
STICH, or Surgical Treatment of Ischemic Heart Failure Trial who
underwent coronary artery bypass grafting with or without
surgical ventricular reconstruction. They excluded patients with
a prior ICD and those randomized only to medical therapy. Over a
median followup of 46 months, 113 out of 1,411 patients who
received coronary artery bypass surgery, had sudden cardiac death
while 311 died of other causes.


                                               
The five-year cumulative incidence of sudden cardiac death was
8.5%. In the first 30 days after bypass surgery, sudden cardiac
death accounted for 7% of all the deaths. The numerically
greatest monthly rate of sudden cardiac death was in the 31 to 90
day time period. In multivariable analysis end-systolic volume
index and BNP were the most strongly associated with sudden
cardiac death. Thus, this study shows that the monthly risk of
sudden cardiac death shortly after bypass surgery among patients
with a low ejection fraction is highest between the first and
third months, suggesting that risk stratification for sudden
cardiac death should occur early in the post-operative period,
particularly in patients with an increased preoperative
end-systolic volume index and/or an increased BNP.


                                               
Well, that wraps it up for you summaries, let's turn to our
feature paper.


                                               
I love our feature paper this week. You know why? It actually
tells us what Tim Hortons, Starbucks, Second Cup and ATMs may
have in common and may have to do with sudden cardiac death.
Indeed, our feature paper actually tells us that coffee shops and
ATMs may be the best spots to place AEDs at, well at least in
Toronto. And to discuss this really interesting paper, I have the
corresponding author, Dr. Timothy Chan from University of Toronto
as well as Dr. Sana Al-Khatib, welcome again Sana, Associate
Editor from Duke University, welcome to you both.


Dr.
Al-Khatib:                    
Thank you, my pleasure.


Dr.
Chan:                            
Thank you, very nice to be here.


Dr.
Lam:                              
So Tim, was that an interesting enough lead up? I mean you have
to tell us about your study, it is so fascinating.


Dr.
Chan:                            
I'm very pleased that you find it interesting and not just us. So
we undertook this study, we started this actually a couple of
years ago, and we've been working on this issue of defibrillator
location optimization for several years, and we've been talking
and we have meetings in coffee shops and we were just wondering
one day, what would be the risk or the coverage provided by all
these different well-recognized location types around the city,
and that was really the motivation that got us started looking at
this study.


Dr.
Lam:                              
Tell us what you did and also how it differs from the study you
did that was published in 2016 where you also reported on the
spatial temporal analysis of registered AEDs in Toronto. The
current study clearly extends it, but could you clarify to us all
how it does?


Dr.
Chan:                            
Maybe just give a little bit of a background and context with
regards to other literature that's similar. There have been
studies in the past that looked at what we would call spatial
coverage of cardiac arrest, so they looked at different broad
location types and they tried to calculate, they basically
calculated how many cardiac arrests happened, let's say within
100 meters of those location types. And what we've done here is
we've extended that in a couple of directions. The first
direction is looking at spatial temporal coverage and so this is
not just in the nearby vicinity, IE, 100 meters, but also that
cardiac arrests happen when that nearby location that had the AED
was open. So if a cardiac arrest happens, but for example, let's
say there's a coffee shop that actually has an AED and that
coffee shop is closed, it's almost as if that AED is not even
there. So one of the major things we made sure to include was
this idea of temporal coverage as well, on top of the spatial.


                                               
The second major difference I would say would be the fact that
we're really looking at more granular location types, so you
mentioned a few businesses in your opening such as Tim Hortons
and Starbucks and so on, which are coffee shops, and so one of
the things that we find is when we look at very broad location
types, we tend to aggregate together lots of different types of
businesses. For example, if you think about a restaurant, there
are many different types of restaurants that get lumped in to
this category, and they do have different cardiac arrest coverage
associated with them. So by breaking it up into smaller location
types, we wanted to get a better idea of the risk at different
locations and if you also think about one of the long term goals
of this work would be to try and help policy makers identify
promising partners to partner with for, let's say public access
defibrillation programs, by identifying specific businesses or
municipal locations, it might actually give them better targets
to try and pursue rather than let's say a group of different
businesses.


Dr.
Lam:                              
That makes so much sense and it really just seems like such an
important public health message as well. The sensible part being
of course, if you have an out of hospital cardiac arrest, you
need an AED that's both nearby and available, so that was really
clever. Sana, could you give us your take on the public health
implications of Tim's findings?


Dr.
Al-Khatib:                    
I think the public health implications of this work can be vast
and if you look at what he's done in terms of ascending to out of
hospital cardiac arrests a lot of initiatives have been launched
to try to improve the outcomes of patients who have the out of
hospital cardiac arrests. Unfortunately despite all the work that
has been done and all the wonderful initiatives that have been
launched, we still have a lot of work to do to improve the
survival of those victims. So certainly a crucial step is how we
deploy AEDs in a strategic way based on data and evidence such as
these data that are provided to us by Tim and his colleagues.


                                               
I think this is very clever, I do agree that we have to be more
strategic in how we deploy AEDs and having the data such as these
will only help us improve and get better of course. Everybody has
limited resources, and so if we can be more selective in terms of
how we deploy AEDs I think that would help everybody. I realize
this was done within Toronto and some of these findings may not
be generalizable to other cities, but I think this is definitely
a great way to make us reshape our thinking in terms of how we do
this, and so a question I have for Tim if I may, are you aware of
any similar studies that have been done looking at this in other
cities and then if not, how do we encourage other groups to do
similar work?


Dr.
Chan:                            
There have been similar studies done that have focused really on
the spatial side of things, so doing this 100 meter radius and
counting cardiac arrests that have been nearby, there's actually
been fairly little work that's been done on the spatial temporal
side. And a couple of exceptions that I will note that I think
are important to point out is there was a very nice study that
was done out of a group in Copenhagen, and they were looking at
actually spatial temporal coverage, particularly the loss in
coverage that you experience when you go from looking at spatial
to spatial temporal. For example if you count all of the cardiac
arrests that happen nearby a registered AED based only on 100
meters, and then you count the same number, but you have to now
layer on top of that when the building that the AED is in is
open, then you tend to get a big loss. They found quite striking
numbers, I think they found a 50% loss, when you look at evenings
and weekends I believe, in Copenhagen. So basically all the
cardiac arrests that happened where you thought there was an AED
nearby, there's actually only one in two is actually nearby and
accessible when you looked into hours of operation.


                                               
And this actually comes back to the earlier question from Carolyn
about how our study relates to our previous study in 2016, so we
actually replicated that Copenhagen study in Toronto where we
measured spatial coverage and we measured spatial temporal
coverage and we measured that loss, and we found a similar loss
overall, about 20%, so 1 in 5 cardiac arrests happened where
there was an AED nearby, but that AED was not available because
that location was closed. So that was one of the impetuses for
leading us to do this study where we start to examine
specifically the different location types and the specific
businesses that were involved.


Dr.
Lam:                              
Wow, that's just really inspiring Tim, I mean I'm kind of
thinking about the Singapore situation too and I think it's
actually applicable and I would love if we had local data similar
to yours, so congratulations, I really share what Sana said.
Thinking though about the public health and the larger
implications of what you're talking about, what do both of you
think of the implications for a public commercial partnership in
these things if it is coffee stores or banks that seem to be the
best locations, perhaps these have implications to how the public
and private should collaborate to make these things happen, what
do you think?


Dr.
Chan:                            
I completely agree. These types of public private partnerships,
specifically for AED deployment are not necessarily new, they
already happen in some parts of the world. One of the examples I
always like to bring out is if you go to Japan and they have
vending machines everywhere in Japan and then you'll often run
into vending machines that have an AED right in them, so one of
the benefits is that first the vending machines are everywhere
and second, if you're a citizen there, you probably know where
the vending machines are where you travel in your day to day life
and so I would say that would be a very similar thing here in
North America, whether it be coffee shops or ATMs, if someone
were to put me in a random part of the city and ask me, "Hey Tim,
do you know where the nearest AED is?" I'd probably have a lot of
trouble, but if they said could you figure out where the nearest
ATM is for your bank or where the nearest Starbucks is you know,
there's pretty much one on every corner. It would be much easier
to identify and find, so I think there are significant benefits
to partnering with these companies or these businesses that have
very broad name recognition and brand recognition, are
geographically well spread and located in populated areas.


                                               
I should also mention, I feel like there's a few other benefits
for these types of locations, so for example for ATMs, I think
there's a lot of secondary benefits, so for example, there's a
built in security component, there's a video camera there, that
might be able to help make sure that no one's vandalizing or
stealing an AED. There's perhaps built in weather protection
because there's electricity there already, so in a cold climate
like Toronto where you might worry about putting an AED outside,
you could have potentially a heating cabinet that would be fed by
the electricity for the ATM and so on. So I think there's
actually a lot of benefits if we could actually operationalize a
system like this.


Dr.
Lam:                              
Sana, do you think there are some more unanswered questions?


Dr.
Al-Khatib:                    
I did want to agree with Tim on what he said, that these public
private partnerships have been in place. Unfortunately we haven't
been able to make much progress. As I said, I do see the results
of this study as being potentially a catalyst to improve the work
that we are doing and ensuring stronger partnerships and
collaborations to help us achieve what we want to achieve which
is basically improve the survival rate of out of hospital cardiac
arrests, so I completely agree with that and I loved your idea,
Tim, when you talked about now people may not recall where AEDs
might be, but if you link them with teller machines or coffee
shops, I think that would be much easier to remember.


                                               
You know of course there are a lot of questions that remain
unanswered unfortunately. Again as was stated by Tim and his
colleagues in the paper and on the call, how we can translate
these findings to other locations I think is really key and then
of course doing the work, meaning let's use these data to deploy
more AEDs and then really looking at the impact of that.
Ultimately we want to make sure that if we hypothesize that by
doing this we can improve outcomes for these victims, we would
want to prove that. So I think the next steps would be to see if
this can be replicated in other places, but also even within
Toronto, if we can accomplish some of this and then examining the
impact, I think would be extremely beneficial.


Dr.
Lam:                              
Fabulous, thank you so much Sana, thank you so much Tim for
sharing your thoughts today.


                                               
Listeners, you heard it right here on Circulation on the Run.
Don't forget to tell all your friends about this podcast and tune
in next week.