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Dear colleagues, this is the role of the European Society of Cardiology
to provide access to the most important scientific information
to all its members and to all its scientific community
Here in Amsterdam, we had a tremendous congress
and we have the opportunity to share with you top scientific data
On behalf of the Board of the European Society of Cardiology
I wish you a very warm welcome to this BEST of ESC 2013
Weel, here we are, I am Keith Fox
chairman of the program at the ESC congress and I am delighted to welcome
you to this live program
what we are going to be doing is discussing with colleagues,
experts in the field, about really what
the different sessions have meant, what particular studies
may influence your practice, may influence your interpretation
and what is really going to be exciting in terms of the future
so, with me I want to begin by introducing my co-chair
Barbara Casadei, Barbara is the chair of the highlights at the ESC, welcome
and Barbara, you are are going to be introducing our panelists
Yes, we are same old Keith and I, and I am delighted
I am delighted to introduce a brand new international panel
I start on my right
Genevieve Derumeaux is from France and she is our expert on imaging
and then we have Marco Rossi from Switzerland who will comment on intervention
Sanjay Sharma, who will comment on prevention, from the UK
and then Silvia Priori, who is our expert on electrophysiology
and also basic science, so we will review
a bit of the basic science program as well
then we have Frank Ruschitzka who will
comment on hypertension and heart failure
and last but not least, Peter Clemmensen who is our expert on acute cardiac coronary care
Thank you very much Great, thanks Barbara, so we are going to start
straight off with the first video clip of 2 important studies, let's see these
The trial design
was actually very simple, to be included patients had to be having
an acute ST elevation myocardial infarction and to have had a successful
infarct artery PCI
they had to have multi-vessel disease They were randomized to 2 groups
1 group has immediate preventive PCI
to the non infarct arteries, the other group does not
462 patients with ST elevation MI
were randomized in PRAMI, after 2 years the results of this trial show that
in this setting, preventive PCI reduced
the risk of cardiac death, subsequent myocardial infarction
or refractory angina by 65 %
It indicates that preventive PCI undertaken during the same procedures
the infarct artery
confers quite considerable benefit about a two-third reduction in serious future cardiac events
The TASTE trial,
thrombus aspiration in ST elevation myocardial infarction
was conducted in Sweden, Iceland and Denmark and we looked at
or addressed the question, does
thrombus aspiration save lives?
Using a novel registry-based concept, the study included
7, 244 patients with STEMI randomized to PCI
with or without thrombo aspiration
The results on the primary endpoint of 30 days mortality showed a neutral effect
of the procedure
2.8 % in the thrombo aspiration group
versus 3 % in the PCI alone group
So we have a very clear message from the the TASTE trial, we asked one simple question
is thrombus aspiration life-saving?
and we had one very clear answer, no it is not
So 2 trials, clear messages, but how actually do we interpret these
we are going to start by discussing PRAMI, because we know that
any trial that stopped early, we got to be cautious about
this is not a very large trial
let's turn to you Marco, how do we interpret PRAMI, is is this the strategy
that is currently used?
Yes Keith, I think this is a very important point so the trial
enrolment was planned to be 600 patients and at the end was
approximately under 450
so we have very little events at the end and is important to underscore the
the strategy that was
addressed what either PCI of non
culprit lesion at the time of acute STEMI intervention
or no procedure at all for the non culprit vessel, these may not be what most of
the physicians
clinicians would do, namely a stage procedure
Ok, so it's conservative against do it all at one stage
rather than staged or even ischemia driven
Exactly, only 2 out of the 4 possible strategies were investigated with this trial
and is important to know that there is another much larger trial
COMPLETE trial, which will enroll approximately 4,000 patients
addressing the same question, so I think the results are very
important but I would describe as hypothesis generating
Ok, Peter is that your interpretation?
Yes, I totally agree, but also I think we have to remember that this is challenging
the current guidelines has a IIA indication
to only concentrate on the culprit artery
So, I think this is very provocative
To turn over the guidelines, we really, and both are saying, we need pretty
robust evidence
Exactly And there are other trials underway
I would wait for the affirmative larger trials that are ongoing
the COMPLETE and the PREMULTI which is part of the DANI 3 program
So even though there's a result
with lots of 0 in the significance
and cardiovascular death, MI, are we not just being too cautious?
Maybe
the future will tell Ok You cannot push me further
So Barbara, let's discuss the next one
TASTE, what a trial, what an imaginative way of looking at registry
using registry instead of just auditing practice
but also doing something
that is better and less expensive, a wonderful thing
what I am puzzled is about the results
my colleagues are always showing pictures of all the garbage
that they aspirate
it makes the cardiologist feel good to take all that thing out
why this does not help the patient?
Because, I think in the past we have relied
again on quite small trials, so I think the discussion we just have
is also relevant
actually to the TASTE, and interestingly enough I think
from the registry they already had a signal, when they looked retrospectively
in the registry
they saw that thrombus aspiration was not
favorable to patient and then they took the consequence and did a large
clinical trial with hard outcomes, this is how it should be done
But locally in the artery
those of us working in coronaries
we know that often times the result is unpredictable
it's not always you really can predict whether you can aspirate
a thrombus or not, sometimes you actually might push it further
down stream and get distal emboli, at least one good thing about this trial
show that it appeared safe
That's right, no stroke, no excess of stroke has was shown by
the previous meta-analysis
Yes, but this is still a little bit counter-intuitive I would have thought
that taking it out
would have resulted in an advantage, but clearly
the result is no
Again, routine thrombus aspiration, so or sure we can say now that routine
thrombus aspiration does not work,
wether it might work in selected patient population
remains open, also in this field there is another large scale trial
ongoing, the total study approximately the same size
but this is difficult for me to imagine that this will
overrule the result of the present study So, here we have a study
that is bigger than all of the others that have been conducted today
put together... and this is the only one that address clinical event
...and does this change the guidelines? I'm pushing you
It should We will have
new issues, we will have to rewrite the guidelines
for the next edition of the STEMI guidelines
So routine aspiration would not be recommended
Yes, in selected cases, it appears safe Which selected cases?
Well, I don't know because if you look at the subgroup analysis
they was no particular sub-group that benefit
I was surprised that the right coronary that has this big
second segment, that usually those of us working with angiography
has a lot of thrombus
with no really side branches, and even in the right coronary artery occlusions,
no effect whatsoever Wait a second, what we've seen is 30-day outcomes
when we first of all looked at the reperfusion studies, when we were doing
those reperfusion studies, there was no benefit at 30 days
Is this too early? Well I think it's difficult to imagine a later
mortality benefit
and I think the other important thing of the study is that we cannot say
they were selected patient because
60 % of all patient that
presented with a STEMI in Sweden during enrollment time
of the study where included in the study, so really these are consecutive patients
I think you have very strongly data and routine
thrombus aspiration cannot be recommended But the mortality is very low
in those who were not randomized the mortality was about 10 %
versus 3 %
Actually, almost 12 % So there is a big difference, so it is not all patients
But, it is difficult to do better than that, I mean enrolling 60 % of all
the patient presenting in a country
you cannot beat that
You tell me which standard trials managed to enroll 60 % of potentially eligible patient
Not only that, but
they have 100 % follow up
yes, which is absolutely terrific
Here we have a paradigm of how trials may be done in the future
ACCOAST randomized 4,333 patients at the time of
non ST elevation ACS diagnosis to either pre-treatment
with prasugrel 30 milligrams or placebo, 24 hours prior to going to the cathlab
Actually, the results show that there is no benefit for pre-treatment,
there is absolutely no
difference in terms of outcomes between pre-treatment and no pre-treatment
and there is a price to pay for this pre-treatment which is an excess of
major bleeding, there was a 2 fold increase in major bleeding
So Peter, a counter-intuitive result, pre-treatment
with an effective p2y12 antagonist,
no benefit, more bleeding, why?
Very provocative, because this is actually something that is being done
routinely in many places
pre-treatment, so here we have a large trial demonstrating no benefit at all,
why, I think that in discussing this
you have to appreciate that there must be interaction between the 2
I think it's an issue of prasugrel
a very potent p2y12 inhibitor given early, and a quite
early intervention where the drug actually has kicked in
and is already effective, so that
I think explain the bleeds Ok, so you can imagine that maybe the treatment time
wasn't long enough to see benefit
but this hazard, you think the hazard is the interaction between
the prasugrel and the other agents that influence coagulation
I speculate, because these patients were also given heparin
of course
so, they were on a rather aggressive
anticoagulant and antiplatelet treatment
and got early intervention, we've seen that, this is
way off, but we've seen in some trials in the past that when you do very early
bypass surgeries on "hot" patients
with ACS that you might not have the most favorable outcome
But the buzzing issue actually is that bleeding was not
so much observed in terms of access related bleeding that somebody
would expect, but also
GI bleeding and other internal bleeding so these remains to be explained
So, it is not access site it is systemic bleeding
this also support Peter's point that it could be an interaction with the
anticoagulants that are on board
but, you know, the cardiologists out there
he or she is now saying, ok, we shouldn't give prasugrel up front
but what do we if we are using ticagrelor
Well, I think there's a clear message here
that has not been tested, but I think we should not
change a strategy in patients with non ST presentations
of ACS
but rather continue to pre-treat with ticagrelor which was shown so
clearly in the PLATO trial
to be beneficial so I think that would be the strategy
Even if it didn't test pre-treatment versus
on the table I agree, it hasn't been tested, but
it plays more into resonance with the daily clinical
practice that we see these days
that these patients, who don't have ST segment elevation when they come in
usually, in most European country, even the most resourceful
wait for a day, 2 day, 3 day before transfer to a cathlab
I think if these patients were in a part of the world where they still use
clopidogrel
and the patient been diagnosed on arrival
should they wait untill they go to the cathlab or should they be treated on first diagnosis
Very provocative, with clopidogrel, who knows, we don't have any data
there's a
recent meta-analysis that suggest that also with clopidogrel
no huge benefit
of giving a pre-treatment But even with ticagrelor
so actually this study really challenges the class I indication
for pre-treatment, but it remains
open whether a longer pre-treatment time
maybe beneficial, so this trial actually does not reflect current clinical
practice and actually the trial
mandated coronary angiography within 24 hours
so the median loading time
to angio was only 4 hours,
wether another result would have been appreciated
with a longer delay remains open
Marco, that's a great point because I think you also have to appreciate that
in this trial
even the patient that went on to PCI did not
derive a benefit, this is what you would have thought, that the patient had a
early pre-treatment
clear-cut ACS, went on to PCI
where prasugrel in the past in ACS
has shown to be effective, that will be sort of the sweet spot
the ideal population, and even that population you didn't see
Maybe the take-home message is that until
ones doing the PCI, when you need effective antiplatelet
and anticoagulant on board, we're a bit uncertain about the up-front
we know the strategy in PLATO worked, but that was the whole strategy of treatment
and your take home-message is, that if you're currently
starting your treatment from diagnosis
with ticagrelor or possibly clopidogrel
don't change that That would be my take-home message
My additional take-home message would be, if you go the same day to the cathlab
don't pretreat your patient Ok, and so what should give them?
Nothing Nothing at all?
Aspirin, anticoagulant, but no p2y12 inhibitor
until they're in the cath lab If you take them the same day, if you take the
day after, you don't know
So good news, life getting simpler
Especially for the surgeon, the surgeon will like it
we have got to be friends with our surgeons
We will get so some data on pre-treatment with
ticagrelor in the ongoing ATLANTIC trial
but this is in STEMI patients, so this is not the same population
it is a different cohorte they are younger
may be less prone to bleeding because of the age issue
So watch for this in the future
Right Barbara, we need to turn to the next segment
The next segment is guidelines
we're not going to review all the 4 guidelines that have been
presented at the
congress but we will see some snapshots that we will then
discussed later, so if we start with the video on guidelines
The key word can be friendly,
simplification, practical use
in order to achieve this goal of simplification and to be
really practical, we made the classification based
on ECG, namely the clinical presentation
If you look at previous guidelines they were 2 targets
now the target systolic blood pressure is 140 mmHg
for nearly all patients, for diastolic blood pressure the target
is 90 mmHg except for diabetic patients in whom
the target is 85 mmHg
There is something new with
this table that we provide the physician to evaluate
the pretest probability, according to this
probability, you go to the test
and the test we have promoted is the stress imaging test
The really hot messages is that therapy and management of people with diabetes and
cardiovascular disease has to be individualized
involved in that is new individualization for glycemic control
which is less tight now, but still there for microvascular disease
We are starting with you Silvia, a lot of patients with heart failure have atrial fibrillation
but the benefit of having CRT on patients with atrial fibrillation has been
not so clear, a bit mixed
so pieces of new recommandations in these guidelines, do you think is backed
up by strong evidence?
Well, I think that you touch a very important point and I think
that these guidelines are making an
advancement in puting clear recommendation on how to manage these
patients
even if we need to keep in mind that the randomized clinical trial, or more than
one randomized clinical trial are not available
so, one of the reason why atrial fibrillation associated with heart failure as
made a bit
complicated to define the effect of CRT
seems to be related, and these guidelines really go in the detail to try to account for
that, and support that with evidence from the literature
the fact that there is not complete capture of the biventricular pacing
and that is really consider nowadays
key for influencing the outcome
so, we are now saying in reading in these guidelines that we need to be
as close as possible to 100 % capture of the ventricle
and these goes to the point that there is a recommendation for
atrial nodal, AV node ablation for ensuring that there is
this very complete capturing
so the recommendation is a class 2a, it reflects the fact that there are no
randomized clinical trial but it points to the fact
that we have several large studies that supporting this
and in this respect is worth mentioning that the CERTIFY study
led by Maurizio Gasperini is being presented at the ESC, is a new study
and the study really support the point that patients with heart failure
permanent atrial fibrillation
who are undergoing AV junction or node ablation
and CRT have the same outcome than sinus node patients
while the patients who have heart failure, atrial fibrillation
and are taking medications to control the heart rate has
almost twice the mortality so, I think that this is an important point, that's
direct in the direction of trying to focus on these
permanent pacing, effective pacing, and
to go and think about AV node ablation This is almost too good to be true
having patient with atrial fibrillation who have the same prognosis of patients
in sinus rhythm
Yes, I think that we need to back up with
more robust evidence but this is encouraging considering how
symptomatic these patients are
and considering that they are at least 25 % of the population with heart failure
so not a small number
Frank do you want to comment on that? I think you're absolutely right
it's an enormous potential there these are highly symptomatic patients and
one-quarter of our patients with heart failure have atrial fibrillation
during the course of their disease so there is enormous potential and I really
don't understand why we haven't seen a trial that
we had some great acronyms for that, CRT in afib
I think that we should do that and we heard with interest now your new
approach of trials
there is a need for an investigator initiated approach to address this issue
because I want to have it up lifted from a 2a to a 1a
because that is an invasive procedure, there is side effects
you know these patients carry 4, 5, 6 years of the course of their disease
an implant with all the side effects
and this is also costly, so I would rather based that on a 1a indication
based on a trial
then on a 2a, they were good trials we've seen, but there were
not powered to really give us a definite answer yet
and the point is also that making a person pacemaker dependent
for life is a
big decision, so it definitely deserve a strong evidence We cannot afford not to have a trial
on this
So, staying on the guidelines and talking about the
new guidelines on hypertension
there is a more conservative takes on the level of blood pressure we should achieve
which would make a lot of cardiologists happy
wether that is good for patient as well
you may want to comment on that, the other thing that is very
interesting is this renewed stress
on starting patients at high risk and severe hypertension on dual
therapy and my question will be
well if we have already decided that they are at high-risk
and a require a more aggressive intervention why don't we throw
a statin as well
and we stop this really costly stepwise
approach in primary-care, can we afford it these days anyway?
All excellent points, Barbara as I said several times before
I am a football fan and I called it hypertension is coming home to cardiology
and actually, we cardiologists were pushing for that, we cardiologists are
happy about these new targets
140 over 90, just below that is fine
the days that we squeeze it down to 120/80 and they couldn't stand anymore
we knew intuitively that couldn't be right in a patient with CAD
these days are over thanks to the ACCORD trial
so, I am very happy with these
more conservative, less aggressive guidelines
just below 140 is perfect the other point you made
is also important, that I think we now should start
in patient with a stage II hypertension
its totally appropriate to go for a combination
therapy instead of going for what I call a sequential mono-therapy
and wasting unnecessary time to get
the blood pressure at target you are right, the question though is
and there were a little be too conservative for my taste
as a cardiologist these guidelines
which combination would you then favor?
what are the drugs there? and there is a shift in these guidelines
back then we were just obsessed with numbers, I think just lowering blood pressure
is not enough
what we cardiologists pushed for, that's why it is coming home
is that we want to see the lowering of blood pressure translate into meaningful
benefit
we have to lower not only blood pressure, we have to lower MI
and improve survival, lower mortality, and that actually has only be delivered by
the ACE inhibitors, that's why I personally thought
that should be a stronger statement on that in the guidelines
but that's up to discussion
I'm happy with blood pressure lowering first and foremost
even though I'm a cardiologist
the other thing, that is bringing cardiologists and intervention
into
the field of hypertension are the data
on renal denervation so there where follow-up data as this congress
and they look as usual, fantastic
and then there are ambulatory blood pressure monitoring data
they look not so exciting, right, maybe the
kind of blood pressure reduction that you will see with one anti-hypertensive
agent
and a lot of variability indicating that maybe there are a lot of
non-responders
so this is a technique that has been embraced heartedly by the whole of
Europe and I was wondering
does it pass the gramy test, would you do it on your own grand-mother?
Well, it's a question whether I will just do it in my mother-in-law
no, I hear you
but seriously, it is somewhere between hope and hype
but what Silvia said before, you know with atrial fibrillation
in CRT, we need the trials and just lowering the blood pressure is not
enough
we have to move from the numbers to outcomes, I want to see
that my patient on renal denervation with resistant hypertension
lives longer and better with it and we're not there yet, these trials are
coming
untill then, it's somewhere between hope and hype
but I agree with you, we also
should treat our patients with resistant hypertension more adequately
they need, while as always say, ACDC, that's an ACE inhibitor
a calcium antagonist, a diuretic combination, that's so to say their highway
out of hell
in resistant hypertension, and make sure they have the good drugs
and that's what the guidelines say, and once they adequately treated
then they consider renal denervation as a promising
therapy, that's what it is
they take the drugs, and there is no way that this patient was called
non-compliant, well we rather cure you with the renal denervation
because we lower blood pressure but we do not know whether we reduce
MI and other hard outcomes, we have to do this
more trials, this is a little bit the mantra I learned from this congress,
trials we need more trials
But they are on going trials in this field Of course, they are SIMPLICITY 3
But, we have
a lot of off-label use now and we have to be cautious
otherwise we will killed this very promising therapy, I think it's spectacular
it's mindbogglingly interesting, I love it but
we have to be careful and do the trials first, be cautious, I agree with you
So, some really important messages there
We are going to move from that to stable coronary artery disease
now may be not as dramatic as
the denervation, but how one investigates the patient with suspected
stable coronary disease, really important
Genevieve, the guidelines have downgraded
the old approaches, what should people do?
Well, this is a very interesting point in these guidelines with the weight put
on the pretest probability and this is quite important new
to adress the potential test
in the patient with intermediate
pretest probability, so this is the first point to be aware
then the imaging community will be probably happy
to know that, even
if the exercise test still remains an option
it should be preferred, and this is clearly announced like that in the guidelines
to use the imaging test and this is a very important point also which is
addressed in these guidelines
is to take care of radiation using this
imaging test, so this is quite important
especially when you're dealing with young people
So imaging test and reducing radiation
Another interesting point also for the imaging community
is that for the first time appears in the guidelines
for detection of coronary artery disease
new technologies such as tissue doppler imaging and stream
imaging in order to a unmask subtle abnormalities
that you cannot assess when you're looking at regional myocardial function
so this is also an important information
Sanjay, you're an expert in
athletes, in exercise, in all these aspects, you evaluate a lot of people
where there is
maybe a query about coronary artery disease
what's your interpretation of how we should go?
Well, I believe that people who are at low risk or have a pretest probability between 10 and 21 %
should probably undergo a CT coronary calcium score
it's a great rule out test and with advances in radiation, we
demonstrated that it's minimal, the amount of radiation received
and it obviates the need for anti-platelet agents and
statins, so my take-home message is that if the calcium score is 0
that is the end of the story in low-risk patients and of course the problem is that once you
have calcium in the coronary arteries
we go back to the same strategy that is imaging,
stress imaging And Genevieve, say something about
the skills to maintain the quality in the echo interpretation
Well, it's very important in a lab to be first of all reproducible in the analysis
to have the skills in performing stress test and the best should be
to use exercise tests and this is preferred also and mentioned in the
recommendation
but also you have to do with the availability
of the tests that are in your institution and the skills that you have in your
institution,
so exercise imaging test are probably the one to be preferred
but the probably most easy way to do is dobutamine stress
echocardiography which is quite largely
used in many institutions But, I think the take-home message for the wider
community is
there is a real problem with both sensitivity and specificity
on what people were doing before
with standard exercise treadmill test and ECG
and thats not good enough in this day an age, do you agree?
Yes I agree, but I think that we
can improve the sensitivity with
developing skill in the
in the physician who are doing the imaging test
I am saying with the original exercise ECG
and we have to mention a specific population
who are women, that's a population that deserve specific attention because
the presentation of the coronary artery disease and the symptoms
is sometimes difficult,
and this is a population
in which the exercise test may lead to wrong conclusions
The same is true in older patients
If I have to highlight
what's the role of multimodality imaging in
the selection of patients who may be refer for TAVI
I would say that multimodality imaging plays a central role
the first imaging technique to use is echocardiography
because it will tell you wether that patient has severe aortic stenosis
or not
and also if there are other factors that may influence your outcome like
for example
a poor ejection fraction or
associated valvular disease and later on, you need to use multislice CT
in order to improve your selection of the prosthesis size, and always going step by step
I don't think that the approach of multimodality imaging
has increased the number of patients who are referred for that therapy but
the results of the therapy themselves
So, some messages about multimodality imaging and, what I take from this
is that we don't do all the investigations in everyone
we take a staged approach, Geneviève is that your approach?
It is clearly the approach and this
talk perfectly illustrates this point
I think that we need now to go to a sort of personalized imaging
diagnostic tests for patients, and especially
in the heart team, where we need to
add skills from imaging
to interventions
and TAVI perfectly illustrates that
with a need for a perfect selection of the patient, a perfect selection
of the way to do the procedure and a perfect selection
to the identification of the good valve to be implanted
so, it may help in
improving the selection of the patients
the outcome of a procedure and
in an organization, I think that's the future and that's the way to go
to have integrated an imaging team
in order to select the optimal technique
to answer the right questions So, we've taken on board
the need for the heart team and you're emphasizing the imaging team
we're not competing with each other but what is best for the patient
And I would say that
within the ESC, we have taken this point very seriously by gathering together
all the imaging specialities within only one association
in order to help this dialogue to be performed and not to compete with each other
I would say as an interventionalist
we really had to undergo a mind change
because initially we believed that angiography
will have all the answers and actually TAVI is a perfect
example where indeed it was not the case
and actually, if we see that now there is steadily improvement in the results
imaging has a lot to do with that
because the 2 most important complications
of TAVI intervention, namely paravalvular aortic regurgitation
and access side complication may be reduced
if the patient is really screened well with multimodality imaging techniques
And I would go further in saying that too we have also
a lot of other aera of intervention where
the combination of imaging may help, the search for the treatment of
hypertrophic cardiomyopathy,
mitral regurgitation, and so on
the notion of heart team
is clearly important to take into account
Indeed, for a structural heart intervention now the imaging guy
is part of the team in the cathlab, clearly So, some clear messages
now, Barbara, as well as the guidelines
they've been 2 large trials in diabetes
presented at this congress and people are digesting
what do we make of it? I think there is an obsession with numbers
as usual
there is a focus on having a certain
glycated hemoglobin level and
always hoping that would affect macrovascular complications in diabetes
but this is
not happening, not only that but there is
a suggestion that there is harm
You are talking about the heart failure Silvia I'm talking about the heart failure
signal in the SAVER-TIMI trial of saxagliptin
So what should we do, Frank what should we do about these big studies?
Well, in diabetes they are
as Barbara said, probably a little bit carried away with all these numbers
there were days where the diabetologist... We are talking about glucose
yes, they were talking too much about glucose probably
and there were to happy when they could lower their HbA1c a bit
then my endocrinologist back home, they were happy with that
but whether that lowering of glucose translate into
meaningful clinical benefit
does it lower MI, stroke and mortality? That's a question, it doesn't
this is what these 2 gliptin trials presented at ESC showed
well the endocrinologist would walk out of the room and say, great
we lowered glucose and we didn't do any harm
except in the heart failure, the cardiologist would say
what's all this glucose lowering for if it doesn't do MI, and stroke and the
mortality
and, in the contrary actually, even increase heart failure
so, some people say, I would rather have my glucose lowered
and they weighed that more important than the heart failure
I think
we have to reshift that a bit But microvascular complications are also
important and they are glucose dependant But they need to be shown for the new DPP4
That's true, but traditionally, we could say that
the lowering glucose decreases microvascular complications
but the thing is, shall we say then that glucose is not a good biomarker
for macrovascular, cardiovascular events?
Well, it's Ok but in diabetology I think we have to tell them hypertension
ACE inhibitors I don't think it's Ok
Well, I think first comes that the best benefit comes from a good ACE inhibitor
and a good statin, and the glucose... Take one step back...
we're asking whether glycated hemoglobin
is a marker of macrovascular complications
Is is not Sanjay, you know about this
I don't think so, it is fair to say that
good glycemic control certainly benefits
at microvascular disease
but these benefits are yet to be realized with macrovascular disease
in fact, I think we need to ease of on the sweet spot
and probably focus more on other risk
factors for atherosclerosis
because in high-risk individuals, there is
evidence that insulin, long-acting insulin, have precipitated myocardial
infarction
and now the glitazones and the gliptins have been associated with
heart failure
They seems actually to be a class effect of glucose lowering drugs
and the risk of heart failure, when you look at pio and rosiglitazone
and now
we've seen that with one of the gliptins of the the trial presented
but I agree,
HbA1c isn't probably not a very good
risk marker, that was outlined in the editorial of the NEJM as well
And wearing your prevention hat, Sanjay
the diabetes patients, are we doing enough in cardiology?
You ask a good question, I think we're not doing
as well as we should be doing, we are focusing too much
on pills, but I think we need to focus more on the metabolic syndrome
which we are not very good at doing in cardiology and I believe, my favorite
subject of course,
is we need to push a little bit of exercise on these people
to help improve their metabolic profile
A little, a bit, a lot? How much exercise?
Well, that's a good point, I would say if they walked briskly
for an hour a week That's all?
Yes, that's not a lot They would reduce their risk factors
their risk for cardiovascular diseases significantly
not to mention all cause mortality And the evidence for that?
There is plenty of evidence, there's a data that goes back to the 50s
by Morris, that was published in The Lancet and more recent data
based on 420,000 person-years, that have shown that for every met
exercise you reduce your cardiovascular risk by 13 %
So, we've got a real challenge in translating this out for the broader
population
because people are doing less It's the best prescription
that we can ever offer our patients it's better than a statin
than everything else, every device, every intervention, it's free
it doesn't involve a weight on the NHS or other
governmental service
So, Genevieve, do you prescribe exercise? Of course
first of all, I begin by myself, no more car, I am walking
but I think that says, a very interesting information coming from the
murine models
because it supports what was said before, when you have
a murine model of diabetic cardiomyopathy
once you have normalized the glucose
you still have myocardial function abnormalities
and on the other hand, when you have a murine model
of exercise, even they are getting older
they improve their myocardial function
with exercise so these mices are helpful
yes, it's a positive message
RE-ALIGN is a phase 2 study in which patients with mechanical heart valves
were randomly assigned to receive either dabigatran or warfarin
We initially planned to have 400 patients
to test this dosing regime, but in fact the study was stopped prematurely
because of an excess of thrombotic events
and bleeding complications
They were clearly more thrombotic strokes
with dabigatran, although it is a small study, a negative study
the message is very clear, you should not prescribed
this agent for patients with a mechanical valve
and probably, if this hypothesis is also correct
you should also not prescribed the oral anti Xa
in patient with a mechanical valve
So, Peter, dabigatran works in atrial fibrillation
it's better than warfarin in the higher dose
in the atrial fibrillation studies but it doesn't work here, why?
I think certainly by inhibiting thrombin
you only do one step, so I think probably the secret to this is also,
they've discussed the author themselfs, is that
warfarin works on multiple pathways
of coagulation, contact pathway
but also tissue factor, I think this might be the secret
and I would agree with Pr Van de Werf, stating that you should really be
cautious about the possible effect or lack of effect
with factor Xa inhibitor So contact activation is
really a an important issue That seems to be so for the mechanical valve
Have we learned from the basic science? Of course, we have learn
from the basic science, I'm always very defensive when
they say that we were misguided by the studies in animals, but actually
if you read the papers, the risk was there in animals
and also we should really start to do animal studies in the same
with the same rigorous methods that we use for
human studies now if we want to then translate these results into
clinical investigations I think the risk was already there
But there's a strong message here, do not use this
in patients with a mechanical valve
however, among the atrial fibrillation population
about 20 % have some extent of valvular disease
and they're included in those populations
so it is mechanical valves that are the exclusions
We enrolled 740 patients with advanced
heart failure and after enrolment
and implantation of a defibrillator or a CRT device
patients were randomized to receive standard care
or home monitoring supported telemedical care
After one year, telemonitoring
demonstrated a significant impact on the PACI score primary endpoint
with a significantly lower total mortality rate
of 3 % versus 8.2 % in the control group
We can do something for heart failure patients using this technology
we simply have to do it right
we need a high degree of automatisation
home monitoring has it, we need short
time lines and good flow of information
and we need a good chain of information
back to the patient, that something is changing
We aimed to demonstrate that
CRT is of benefit of patients with mechanical dyssynchrony
and narrow QRS
809 patients with heart failure who has QRS below 130 milliseconds
and mechanical dyssynchrony assessed by echocardiography
were included in Echo-CRT, ICD were implanted to all
and randomized to CRT ON or CRT OFF
The study was stopped prematurely for lack of efficacy and potential to harm
with a higher total mortality rate
in the CRT group
We found a surprising increase in all cause mortality, p value of 0.02
we showed that there was an increase in cardiovascular mortality actually
driving all cause mortality
what we could show and demonstrated today is that there is certainly
not a benefit of CRT in the narrow QRS patient, that the ICD is the appropriate
therapy for these patients
Again, very clear messages So, Frank, is the automatic telemonitoring of patients with heart failure
the state of the art now
Well, not yet, we have to wait for the final paper
finally, some good news from the telemonitoring front
and finally some light at at the end of the tunnel
What is making this different from the trials that failed before?
You know, there is an automatism with this home monitoring device
the patient does not really have to do anything, so the compliance is
100 %
it actually triggers an alarm button at those who
look after the patient and then they trigger the intervention
and that's actually exactly
what I still didn't understand from the trial, and we have to learn from the paper,
which is hopefully coming soon, what triggered
the event, was it the afib, or whatever it is,
and what really
they did, and what kind of intervention took place
which kind of help them reducing the events and that was quite remarkable
No, it's not a state-of-the-art yet it's very interesting, very promising
device, it looks spectacular
but I think we have to wait for the final paper
to see that, but then we have 2 negative studies, 1 positive
but it's coming, they're getting more sophisticated, they are getting better
So Echo-CRT, I think we need to take the Echo off the title
because that is a study that shows that the demise of imaging in
the stratification of these patients, it is all about the QRS
That hurts me, Barbara
I think that's what the results show, for sure
the other thing that is a little bit puzzling is the mortality,
you have an increase in mortality
and is not associated with an increase in hospitalization
suggesting maybe arrhythmic death
or other form of sudden death in these populations, how do you explain that?
or is it do you think, just some findings that need to be
confirmed
These are excellent intriguing points Barbara
when Johannes and I designed the trial
there was back then in 2007, long time ago, many people told us that
the vast majority of those with a narrow
have echo sign of dyssynchrony, there are single-center studies
and huge off-label use, 1 out of 5
1 of 5 CRT implanted in the last years was in patients with narrow
so there was a huge rational out there and now we close the chapter
It required definitive outcome assessment
and that's once again something Silvia said before with afib, here we showed it
we have to do the big trials, before that we don't know
and with Echo-CRT, we did an adequately powered trial
115 centers worldwide, we closed the chapter and it hurts me because these patients
are many, these are the majority of heart failure patients, we're running out of option
they have a prognosis worse then cancer and I'm sad that I can't bring them CRT
because we shouldn't forget one thing, CRT is a life-saving device
and we under implement that also in patients who have a clear-cut indication
in the wide QRS, we learned one thing from Echo-CRT on top of that as well
ECG is back in the ring, the echo is out, it's ECG that rules
So, 130 milliseconds is the guide?
Well, 120 we know
because it was very narrow in our trial, the main QRS was 105
with 120, it's dead below that, we know that
above that, 120, we have still a Ia indication
don't forget in CARE-HF, the mean QRS was
around 150-160, there's a clear evidence but still there, we do
not enough CRT, we should do more there
The biomarker in cardiology 8 study was a process study, a prospective
randomized study
and we used the biomarker copeptin
In the BIC-8 study, 902 patients
with suspected acute coronary syndrome but
initial negative troponin were randomized to
either the experimental procedure with copeptin measured on their
initial blood sample or to the standard process
We looked as major events as the primary endpoint
When we look at the primary endpoint, for MACES at 30 day
and we found that the MACE was virtually identical in both arms
5.5 % in the standard group and 5.4 % in the copeptin group
Comparing the both study arms, the standard and the copeptin arm
we saw that 66 % of patients in the copeptin arm were directly
discharged from the ED
versus 12 % in the standard group
So Peter, clear message? I think so, although
again, a rather small trial, but finally I think we really have a promising
biomarker
remember how many biomarkers have not made it
to this stage, so I think it's promising and also I think the linkage between
the troponin
looking at myocardial necrosis and copeptin being linked to
heart failure mechanisms is intriguing
An early rule out, clearly important, a big proportion of patients presenting
and the current guidelines saying high-sensitivity troponin
0 in 3 hours, now here's another player I agree
The genetic cardiomyopathies in particular
can be generated by a number of different
genetic mutations, so one way to overcome this difficulty of developing
thousand different drugs is the use these class of molecules which are known
as chaperone
this chaperone molecule will basically mask
the mutation, not correct genetically
but mask it in terms of their functional consequences
In this context, the melusin gene was delivered by
adeno-associated virus vector to mice with genetic cardiomyopathy
What we found, is that actually the
mice, untreated mice, developped as expected the cardiomyopathy
but upon treatment with this melusin gene
the mice are retaining their normal function
for a very long time period
An interesting take on cardiomyopathy, but gene therapy has had its up
and down over the years and now is back
almost in the clinic, what do you think Silvia that gene therapy can offer
that traditional treatment cannot? Yes, you're right, gene therapy started
with negative data, mainly because the vector that were used
were not appropriate, now with the advancement of new
tissue specific vector, I think that we are seeing much
faster progresses, for example Glybera is the first therapy based on a
adeno-associated virus
that has come to the market for treating lipoprotein lipase deficiency
in the heart field, you know we have had already safety
trial for heart failure patients with gene transfer
so I think that, if you ask specifically the question
now that we can do it where we want to do, it it's clear that in genetic
diseases
a niche of patients, very selected
with a disease that is lifelong, therefore means
any therapy for the entire life, the curative approach is
very appealing
so, done in a model of cardiomyopathy or in arrythmias as we have shown
all approaches that can simplify therapy, improve quality of
life and survival in these individuals, so I would definitely think that
is the first
set of patients to test I think it's nice to see this progress
Terrific, now I'm gonna ask Sanjay about one of
the studies that hit the headlines in the papers as well as the scientific press
which is Tour de France, and this is the mortality figures in the Tour de France
and
if you only read the headline, it says that if you are able to
run, able to compete in the Tour de France, then you gonna live
7 years longer, now is this because you've competed
or is this because you are selected to be people who were able to do it?
I think this is a very pertinent study Keith, because although exercise is good for you
there are certain practices such as Tour de France, the marathon and the Iron Man
that are very grueling and there is data that athletes that finish these races
around 50 % have high cardiac troponin levels and BNP levels
and subsequent studies in the veteran athletes have showed a high burden of
atrial fibrillation and a threefold increase in myocardial fibrosis
and therefore a possible surrogate that such practice...
so late fibrosis maybe one of the mechanisms that drives the atrial fibrillation
correct, so possibly a surrogate that such practice
may be safe would be to test longevity and that's exactly what the
French group did and they demonstrated a 41 % reduction
in mortality compared with males in the general population
now, this does sound very exciting,
but I've I have some concerns of course, because if you can do the Tour de
France, you are probably
genetically and physiologically superior to people who can't
you are more likely to live a much healthier lifestyle
and one thing that came out that trial was a 72 % reduction from
respiratory disease
compared with the general population, suggesting that they were
much less likely to smoke
very healthy cohort, so I think all we can say is that
if you are able to do the Tour de France
you are likely to live around 7 years longer than the general
population
Ok, so, there's a take a message, now you know Genevieve is prescribing exercise,
you are prescribing exercise,
how much exercise? the good news is that you don't have to be able to do
the Tour de France
to benefit with respect to your cardiovascular system
as I mentioned earlier, there is data that if you jog around
1 hour a week, or walk briskly at a pace of 6.4 kms per hour
you can reduce your cardiovascular risk by 50 %
So, that's pretty impressive!
I want to come now to the take-home message from everyone
and I want to start with you Genevieve,
your take-home message for the audience
Well, regarding the imaging technique, I think that you have to
choose the best imaging technique according to the
clinical question which is raised, this is important
and the other take-home message is
using these new tools, fantastic tools that are available now
do not prevent you for thinking about what is the
underlying pathophysiology behind, because otherwise you can raise
wrong conclusions, this is very important
Sanjay? I would echo exactly how I started
this evening, and that is to encourage all physicians listening
to advocate exercise just as they do
abstinence from smoking for example
and eating unhealthily, so I think exercise should be
an important piece of advice that should be given to all patients that
attend a physician
Frank?
Well, my take-home is that devices are very interesting and intriguing in cardiology
but we learned from Echo-CRT and other trials that
even devices, as interesting as they look, they required definitive outcome
assessments, we need the big trials
even in the device world that's true for renal denervation
for mitral clip, for some CRT indications and so forth
let's push for that Peter?
You pass the ball right to me because big outcomes trial
so I think that the take-home message for my part in acute cardiology
acute cardiac care, would be to stop routine use of thrombus aspiration
in STEMI patients, very simple, but very important and also with great
trial design Silvia?
I would say that with all the trials that we have seen, with positive, negative, contradictory
results as we have discussed
the exercise of compiling guidelines is very important, the ESC is very active
in these directions
and I think that general cardiologists should really read carefully and
critically the guidelines ...and apply them
and apply them of course, I think that is important as well
Marco? I would say that the Scandinavian colleague told us a new
way of performing
high-level clinical investigation, namely this registry based
randomized clinical trials and of course this is something that should be
expanded in the future
but you will need such high level and very good
databases in order to do that
Barbara? Basic science is coming to the clinic
the future is bright
I think now we are really seeing
gene therapy, new therapeutic approaches which of course
will need to be tested but is nice to have a completely different way
So, science and practice is not just for the person at the bench
it's actually for the clinicians
and you know we've learned in this congress that definitive large trials
have turned over what we thought
was the evidence from smaller studies and maybe that's one of the key
take-home messages I want to to close by
thanking all of you, our volunteers for giving up a lot of your valuable time
in this process, I want to thank my co-chair, Barbara for
tremendous insights and all the work in doing this
for the entire team at the ESC staff
for the two sponsors, Servier and AstraZeneca
for supporting the program and also a special thanks
to the national societies who are using this program and translating it
and making it available, but especially for
the audience there, we want you back in Barcelona,
there's going to be even more exciting congress
next year, be there Yes, can't wait, see you in Barcelona
Don't miss the ESC congress 2014 in Barcelona
where everything comes together