(soft music)
- Hello we're here at the
American Heart Association
meeting in Chicago, where circulation
has 19 simultaneous publications this year
and that is a huge increase
from six in the past
to 19, all thanks to the
man next to me but first,
let me introduce myself.
I'm Dr. Carolyn Lam, I'm
associate editor from
the National Heart Center
and Duke National University
of Singapore and I'm the
voice you hear on circulation
on the run but I'm so pleased
to be here in person today
with Dr. Dharam Kumbhani
and he's associate editor
from UT Southwestern and he also leads
the simultaneous publications for this
journal so big applause
for this amazing bonanza
this year next to him we
have Dr. Sana Al-Khatib
and she's from the Duke University,
and finally Dr. Gabriel Steg
from University of Paris.
Wow okay we've got 19
papers to chat about no
I'm just kidding we're going to talk and
focus on the sevens and
simultaneous publications
that were late breaking science.
Why don't you start us off
Darren, we will first start
with the interventional trials and there
were three of them I'd
love you to chat about
the first of them but even before that,
maybe tell us what it's like
to get a simultaneous publication because
I think people underestimate
the amount of work
it takes to do that.
- Yeah no, thanks a lot
Carolyn I think you know under
Joe's leadership you know the whole space
of simultaneous publications
and late breaking
clinical science has really been you know,
it's been a big endeavor
for him and for the journal
and you know we just have an amazing team
that's able to work on this you know in
very quick order so I think
you know for the viewers
I think you know it's
a very involved process
but it's a very gratifying
process you know we work very
you know closely among the the associate
editors, the senior editors,
and then the circ staff
and we have very rapid
turnaround time, so we owe a lot
of gratitude to our reviewers
who you know frequently
will turn these reviews in
within 48 hours and our goal
has been that we respond
back with a decision
usually within five to seven
days and so you know even
so it's been very gratifying you know
then it moves on to next
set of revisions etc,
but even among the papers
that we're unable to
you know except for circulation
you know it's just a quick
turn on turnaround time for the author,
so they haven't lost as much time and
you know can potentially look elsewhere.
So it's been a really gratifying process,
it's been a great great
team effort, I appreciate
you know everything you said
but really I don't deserve all
that credit it's just
it's been a great team.
- No, I know it's been rumored there's a
lot of lost sleep on
your end so thank you,
thank you Dharan for this
and maybe you could open with
the eyesight test for--
- Yeah well, thank you.
I think you know we had
some really interesting
interventional trials and
you know Dr. Steg will discuss
a couple of them as well.
I think I saw a test for you know
was a very interesting trial.
It was one of the it is one
of the first ten trials,
it gets to the ten year
mark, so you know as you know
this is just a 10 year follow-up
results of that we know
you know it was about a 2500 patient trial
it was done in Germany multiple centers
and really they were trying to assess
the space that they
were trying to you know
or the knowledge gap that
they were trying to fill
was you know the durability of
the bio absorbable polymer
stents and so specifically
they were looking at a
bio absorbable polymer
sirolimus eluting stent,
the Yukon Stent and then
they compared that with durable
polymer stents including
Zion or the Everolimus
eluting stent and then cipher
which is no longer we live in the US but
that's a permanent polymer
sirolimus eluting stent,
so you know the primary
results you know published
and presented a long time ago
there was really mace events
at one year and it showed non inferiority
for this bio absorbable
polymers stent back then
so then they had you know
incredibly 83% of the cohort that
they were able to follow
up out to ten years,
and you know what they
showed is that you know
when we can you know I don't
want to necessarily get in on
the numbers and the details as much,
but what they showed is that
this bio absorbable polymers
Sirolimus eluting stent had tended to
have similar outcomes to Zion which we
you know accept a state of the art,
current generations ten permanent polymer
and it did better then the
Cypher stent both in terms of
you know mace events and
stent thrombosis so suggesting
that you know the big advance
in the field for this is,
this is a you know long term
follow up of this of the stent
it suggests that you know
outcomes may be similar
in this patient population
although only 12%
were really enrolled with an
MI in this patient population,
most of them were stable
or less sick ACS patients
and they show you know fairly
good outcomes out of 10 years
comparable to Zion's but
and better than ciphers.
So I think it was interesting.
Gabriel, what is your take--
- No, I think it's important,
there's been a tremendous interest
in international community
on trying to tease out
which are the best types
of stents and beyond brands
try to understand you
know the type of stent,
the coding, the drug that you put on it,
whether the polymer is
durable or not durable
or anything these types
of fairly well done
large randomized trials
belong so from are critical.
And a lot of the focus in
international community originally
was on lumen size, late loss,
angiography parameters
short term and now we
the field has matured and we've
moved to clinical outcomes
patient oriented outcomes,
long term follow up
and it's important because we've learned
from long term trials such
as protect, that the result
that one year may not predict
what happens at five years
and sometimes you have surprises,
so it's really important
we owe it to our patients because these
are irretrievable devices
once you've implanted them,
they're they're theirs we
talk about cipher being
out of the market but there are
more than a million patients
who walk every day on
this planet with a Cipher
in their coronary
arteries so we better know
what the long term follow up is.
- Yeah, it's a great point.
- Wow I mean thanks
also for the discussion
that allows me as a non
interventionist to realize you know
it's hard to keep track of
what's happening with all
the different types of
stents and polymers and so on
but could you then
summarize for the field,
does that mean that these
biodegradable ones are now
(laughing)
I don't know, do I sound
Ignorant when I say that?
But that they're no you
know really in the game,
is that what it does?
- So you know there's this
whole bio absorbable field
you know there are nuances
so this really is testing
a bio absorbable polymer.
- Oh!
- Where so you know with
every stent you have a stent
you have the polymer and
then you have the drug.
- Thank you.
- And so the polymer and
the drug go away and then
you left behind with the
Bare-metal stent and that's
this Yukon stent
- Got it.
- The one that has been
in the press a lot more
is the bioabsorbable
scaffold where the stent
and the polymer and the
drug, everything in theory
should be gone at a
certain period of time.
So this is you know it's an
important distinction though
because I know that you
know it's very confusing
you just say bioabsorbable
and it's unclear if that's
you're talking about the
polymer, you're talking about
the stent itself, but this really was
a bioabsorbable polymer issue
so you're left behind with
the Bare-metal stent at the end of it.
- Got it crystal clear and
thank you. That's cool!
(laughing)
- For electro physiologist too.
(laughing)
- But now let's go into
the AMI field right,
so there were two trials that really spoke
to acute management patients
with coming in with an AMI
and with cardiogenic shock for example,
so Gabriel could you tell
us a little bit about
the IABP shock II trial as well as the
you know really talked
about a door to unload
in pellet row.
- So the IABP II trial is
a trial a randomized trial
looking at the benefit or lack thereof
Intra Aortic Balloon Pump in
patients with cardiogenic shock
and acute MI, and it's been
standard practice since
the 60s, to offer IBP pumping to patients
with cardiogenic shock
and AMI, so literally more
than a million patients have
been implanted with IABP,
but the reality is when we look at
the randomized trial evidence of benefit,
there was none there was there were very
small trials, inconclusive, underpowered,
and professor Thiel from Germany
and his colleagues deserve
enormous credit for having
had the courage to really
do what wouldn't needed
to be done.
A proper, randomized control trial.
Of course open label and
what they found in IBP II,
which they already
reported a few years ago is
that there was no acute benefit of IBP
on survival short term nor
for that matter on many
of the secondary clinical
outcomes looked at in that trial
they subsequently reported
one year mortality.
What they did here is they
gathered follow up on almost
all of the cohort at more
than six years and they found
that the long term survival
is identical for patients
who received an IBP and those who did not.
So I think this nails the issue,
but there's another thing
we learn, the mortality at
six years is staggering it's close to 60%.
And although a large
fraction of the patients die
in the first 30 days, you
still have an additional 10%
of patients who die between
the first year and six years
so it still remains a very
sick patient population
for whom we need to
investigate new strategies
and I don't think it's going
to be necessarily mechanical
we have to think of all of the strategies
we can do to prevent and
mitigate cardiogenic shock
to build up, and that gets
us to the second trial
that I'll talk to about--
- One question though
about that, they said that
they provide any information
about modes of death in these patients?
- Yes, they did capture
information about that,
off the top of my head I'm
unable to provide information
but yes, they did capture
that the German system allows
them to retrieve information
about causes of death
and it's closed system,
it's a national trial.
So they were able to get--
- Is this information
that can help us inform like
what interventions are needed?
- Yes, that's really important.
- And you know to your point
about you know that it's
you use the you know a
very interesting word
you know last nail that's
actually and you know also
how Dr. Hoffman addresses
their editorial which you know
she wrote a really nice--
- The leading expert
in the field.
- And so you know I'm
interested in your thoughts
so you know the use of
balloon pumps for shock
there's a discrepancy between
the American guidelines
and the European guidelines.
Last year the European
guidelines were updated
and it is really such a
practice changing guideline in
that it now this routine
use of balloon pumps
and cardiogenic shock
last three indication.
Which is you know going through training
there was all you had when
someone come in shock you,
you would throw in a
balloon pump and so it's
that's really you know quite
a you know practice changing
you know event.
- Yeah.
So these investigators are
embarking on new studies
with ECMO and I think it's
going to be fascinating to see
whether ECMO which also gets
increasingly used worldwide,
whether there's evidence
to actually support or not
whether this is useful, so
I think it's they are doing
the proper thing, they're
doing the right thing,
randomized trials and we
should commend them because
these are really difficult
trials in the acute MI setting,
shock patients you know ECMO
IBP, that's really difficult
and they are brave investigators,
they're good investigators
and I think they provided the
community with a clear answer.
- And exactly the kind of
papers that we like publishing
at circulation isn't it?
Now what about the door to unload though?
- So you know there's actually
a good segue with door
to unload because if we
can't properly treat shock
once it's there, can we do
something to prevent shock?
can we do something to
preserve myocardium?
And one of the experimental
findings that is very clear
is that if you unload in
experimental myocardial infarction,
if you unload the left ventricle
you reduce infarct size,
and so investigators I've
been trying to translate this
experimental finding into
the clinical arena using
the impeller device and
there's enormous interest
particularly in North
America for impeller use
in acute MI patients with larger and Fox
with the idea that if you can unload
the left ventricle you
might be able to mitigate
this the extensive myocardial infarction
and therefore avoid cardiac shock
and probably improved prognosis.
Although this is a very attractive
theoretical concept, it
still deserves to be tested.
And so if you want to
test it you have to unload
the ventricle as soon as possible,
ideally before reperfusion,
which means that you're going
to have to delay reperfusion
for the time of implanting
the device and unloading
the ventricle and so what
the investigator is in did
in this trial is to study
whether delaying purposely
by 30 minutes reperfusion
to unload the ventricle for 30
minutes prior to reperfusion
was feasible and reasonably
safe and it's a small trial
it's really a pilot trial
by no means that it tests
the proof of concept of the
device or the theoretical issue
but it shows that it's feasible.
There doesn't seem to
be a massive increase
in the total time to reperfusion
because just by chance
the group that was not delayed
had longer time to PCI,
so eventually things
are sort of evening out.
They looked at MRI size of
infarcts at follow up there
was no obvious difference but of course
it could still be type 2 error
so we're not totally sure
about this but certainly
it paves the way for doing
a proper proof of
concept, randomized trial,
testing, unloading versus no unloading
with a true control group and I think
that's what investigators
are looking forward but
I understand there's immense
interest for this concept
in international community particularly in
the United States and
I'm quite curious to see
what this future trial will look like
and what the results will be.
- Yeah and so Gabriel I
notice you were very careful
to frame it to say what the
trial was trying to address
and what it wasn't and there's
been quite a lot of buzz
after that do you agree
with everything Gabriel said
and what have you heard and?
- You know I think I mean he was you know
incredibly eloquent in
you know kind of outlining
the premise of the trial
and what it really showed
I think the one thing that you
know and this was brought up
in the very nice editorial by
Dr. Patel from Duke as well
is you know that it would
have been really nice to have
a control arm which didn't
have any unloading bezels
or not patients with shock
you know that just directly
had primary PCI and then
comparing infarct size
so I think that was one of
the pieces of information
that you know would have
been helpful to then put this
in perspective so you know
when you have an infarct size
of you know 8% or 10%
how does that compare
in the same patient population
that they're testing.
But you know it's you know
you you absolutely right about
you know the need to do
difficult trials like this
where a lot of times you know
it's just assumed to be true
and is embraced in clinical
practice and you know as
I gave the example of what
the balloon pump earlier
where you know as a fellow
you you know you saw someone
in shock and you know your reflex was
to put in a balloon pump
and so I think testing this
you know very difficult
patient scenarios as well as
you know just in terms of
trial execution you know
we really I mean it's amazing
to have two trials on that.
- If I may come back to
this it's funny because
we've been using the IABP
for years thinking this is
what we should do in shock,
now our German colleagues
have proven IBP doesn't work
so a lot of investigators
have reverted saying well,
we should use impeller.
But Where's the evidence showing
that impeller is beneficial?
We have none so I think that's a trial--
- And that's important--
- Yeah, exactly.
- Exactly, and you know
going back to door to unload,
it' important to prove
safety in order to go to
the next step--
- Yes.
- Which is exactly--
- No, I think it shouldn't
be over interpreted.
- That's how it should be.
Exactly.
Received by the community so that's great.
Now let's switch gears of
it Sana so the in EP world,
the EP guided non invasive
radial ablation of VT,
fascinating stuff, what are your thoughts?
- Oh, I absolutely
agree definitely so this
was a phase 2 study that the authors did
they enrolled the 19 patients,
so it was a small study
but it was really helpful remember
if there's a major clinical need there,
these are patients who have an ICD,
who have recurrent
ventricular tachycardia,
they've been treated with
at least one anti arrhythmic medication,
at least one catheter
ablation procedure and then
what do you do with those patients?
This is actually a clinical scenario
that comes up frequently
and we absolutely need
to be looking for more
therapies for those patients
so that's what that
study was about is trying
to explore new ways to
treat these patients.
And to be able to do it noninvasively,
I think is fascinating.
And so that's what they
enrolled these patients.
Patients had to have failed
these treatments anti
arrhythmic medications prior,
catheter ablation and they
underwent noninvasive imaging,
to really localize the source
of the ventricular tachycardia,
where it's coming from?
And then they subjected
them to stereotactic body radiotherapy,
to ablate those sources of
ventricular tachycardia.
And of course the results were fascinating
because they showed on the
effectiveness that this seemed
to be very effective because
if you look at the reduction
in the burden of ventricular
tachycardia and a couple of
their patients actually
had significant PVCs
and PVC induced cardiomyopathy,
there was a significant reduction.
In the the rates of these
arrhythmias in these patients with
this intervention which was great to see,
in fact to be specific
about 94% of these patients
18 out of the 19 had significant benefit,
and in about 89% of the patients
there was more than 75%
reduction in the arrhythmia.
So these are actually really
interesting findings especially
in a patient population
where we really don't
have other options of course
you're going to ask me
about the safety what are
their safety concerns?
Of course this was a primary
endpoint for the authors,
they did look at safety up
to ninety days and they found
that there were two significant
adverse events that occurred
in those 90 days, one was heart failure,
and one was pericarditis
the concern of course
with radiation is what what
else can we expect especially
if you follow the patient's longer,
so certainly we need more
data, the authors acknowledge
that beautifully and I think
their intent is to launch
a multicenter randomized
clinical trial or and maybe
I don't know if it will be randomized
but at least a multicenter
a clinical trial to see
if they can replicate those findings.
So that was very interesting to see.
- Yeah, it was, thanks
that was really exciting
so some exciting Charles in my world
of cardio metabolic disease
too and I want to highlight too
the CARMELINA trial and
the CAMELLIA-TIMI 61.
So first to CARMELINA trial,
now this was a secondary
analysis of CARMELINA
and this was CARMELINA
if I can remind everyone
is a cardiovascular
outcomes trial randomizing
about 7,000 patients with type 2 diabetes
and are thorough sporadic
cardiovascular disease
and/or chronic kidney
disease and randomizing them
to the DPP-4 inhibitor,
Linagliptin five milligrams a day
versus placebo following up for a median
of about two years.
So we know that type two
diabetic patients are at risk
of heart failure and there's always been
a bit of a question mark
when it comes to DPP-4
inhibitors and their risk
for heart failure and so
this secondary analysis
look specifically at the
hospitalization for heart failure
and related events in CARMELINA.
The important thing is that all these
were prospectively
centrally adjudicated events
you know and this was a pre specified
through post hoc analysis
and the summary of it all
is that Linagliptin was not associated
with an increased risk of
hospitalization for heart failure
or the composite of cardiovascular
death and hospitalization
or you know the related
outcomes and importantly
the authors did also sensitivity analysis
and interaction analyses
to show that the results
were consistent whether or not patients
had a history of heart failure
which was in 27% of patients regardless
of the baseline ejection
fraction that was measured
within a year of certain
drug and and also regardless
of renal function so EGFR or
urinary element granting ratio.
So this is really important
because this trial
adds to the growing perhaps understanding
of DPP-4 inhibitor heart failure risk,
the whole question mark
actually came with SAVOR-TIMI
and that was Saxagliptin,
but since then there's
been three of other trials
have shown no heart failure risk you know
examined TEE Course and now CARMELINA.
So an important addition and
I think should reassure us.
And then from from you know diabetes
and heart failure risk
which is always very hard
but now obesity, so the
CAMELLIA-TIMI 61 trial
looked at renal outcomes in this trial,
now what was this trial?
It was actually testing
Lorcaserin and that
is a selective serotonin
to C receptor agonist,
in about 12,000 obese
or overweight patience
and basically the primary results showed
that it did not increase, it
met its CV safety outcomes
with weight loss and so on
but this time they
looked at renal outcomes,
because obesity has been
known to be associated
with hyper filtration of the kidneys,
you get albuminuria and
it's apparently worsening
of kidney disease, so we need to know
is pharmacological weight
loss going to be associated
with improve renal outcomes
and basically that is
what CAMELLIA-TIMI 61 showed
you know their renal outcomes
was a new or persistent
albuminuria and then
the standard doubling of EGFR
or end stage renal
failure, renal transplant
or renal death and that
was improved by Lorcaserin
along with that there was
the anticipated reduction
in way HbA1c and BP, so it does look like
from these late breaking results right?
That we have another tool in our toolbox.
- And for the clinicians out
there like which patients
should they be thinking
to use this medication in?
And what kind of obesity
are we talking about?
At what point did you introduce that?
- Yeah, so this is common
garden just defined by BMI
that was above 27 and I don't
think they're saying to use
it in patients with renal
dysfunction but to sort of say
that to look and see whether
weight loss also associates
with renal function and and
improvement and it does.
So I, it's reassuring. Yeah.
- Yeah.
- And then okay, let's round
up with that last trial right?
And very interesting one
because it's pragmatic,
mobile health and wellness, tell us.
- Yeah it's you know it's
really a monumental effort
so this is you know I'll be brief
but it's really a phenomenal trial it from
an AP standpoint and
implementation standpoint,
so this is from from India
it was a you know coordinated
by the Center for chronic disease control
and the Public Health Foundation of India,
where you know as everyone
knows you know India is now
the diabetes capital of the
world and chronic diseases
have very quickly overtaken you
know other infectious causes
as the number one cause of
mortality and morbidity.
So this was a you know big undertaking
you know really collaboration
from three continents
where everybody was a
community based cluster
randomized trial they had 40
community health centers and
what they were trying to see is primarily
for hypertension and diabetes
that if you implemented
a structure and typically
using this M well care tool,
which is basically an electronic medical
records storage facility and then it also
has inbuilt clinical
decision support and really
for hypertension and
diabetes management but also
they had tobacco, alcohol
screening, abuse screening
and also for depression and so
what they really wanted to do is
so you know very ingenious endeavor
and they try to see of
doing this systematically
at a you know cluster
randomized fashion if
that would actually
influence patient outcome
so they had a little over 3,000 patients
and they followed them for 12 months,
unfortunately the trial itself
as far as a primary endpoint
which was changed in
systolic blood pressure
and Hemoglobin A1C, they had you know
pretty significant reductions
in both arms you know
about 12 to 13 millimeters
which is amazing
from a population health
standpoint in both arms
not statistically too significant and in
Hemoglobin A1C, also by 0.5% in both arms
and you're just suggesting
that kind of having
this more frequent interactions
with you know Medical Health
System itself was driving a lot
of this benefit, so although
the trial itself was negative
for the primary endpoint I
think it's a huge step forward
for the management of
chronic disease, epidemiology
and burden in developing countries.
- Neutral.
- Neutral.
(verbal nod)
Fair point.
- But that you know, we've
discussed this whole array
of seven trials in they're
difficult trusts me,
I mean talk about another
difficult type of trial
to do cluster randomized pragmatic trial,
it's amazing the breath of
simultaneous publications
we've had this year.
Thanks again to everyone
for introducing this,
and thank you for joining us today.
(soft music)
