Best of ESC Congress 2014 – 04 sept 2014

Best of ESC Congress 2014 – 04 sept 2014


On behalf of the European Society of Cardiology I wish you a warm welcome to this Best of ESC Congress 2014 Barcelona has been a tremendous success with more than 11,000 abstracts 30,000 participants and a great scientific programme we are very happy to be able to share with you some of the top scientific news that has been presented here what more to say, let us go to the Best of enjoy this Best of ESC Congress 2014 In this edition of Best of ESC congress 2014 We’ll report on a new drug bringing a paradigm shift in heart failure survival What the new ESC Guidelines will bring to your practice Discover a new class of lipid lowering agent How to manage acute chest pain more effectively And finally we’ll share snapshots of the scientific programme So here it comes, the Best of ESC Congress 2014 Welcome, here we are in Barcelona Just one day after A really exciting and a very large congress But people are thinking now What do the headlines mean What’s behind the headlines What does it mean for our practice What does it mean for the science We are very fortunate To have a really expert panel around the table To help us address this I am Keith Fox and the Co-Chair for this programme is Barbara Casadei and Barbara would you like to introduce the panel? Yes it is my pleasure to introduce our panel and I will start from my left With Genevieve Derumeaux from France On my right, Frank Ruschitzka from Switzerland, Hector Bueno, from Spain Silvia Priori, from Italy Sanjay Sharma from the United Kingdom and Marco Roffi from Switzerland Welcome to Best of ESC So there has been an enormous amount of excitement at this congress and a lot of excitement has come from new treatments in heart failure So if we are ready with the first clip we are going to see what has been shown at this congress Two pieces of good news for patients with heart failure CONFIRM HF randomly evaluated the impact of iron deficiency treatment by ferric carboxymaltose on clinical outcomes among 304 patients with heart failure and iron deficiency We confirm that the treatment of iron deficiency is very effective It improves patients symptoms, exercise tolerance quality of life and may reduce the risk of heart failure hospitalisation This is extremely important because it translates into a context that we need to seek for iron deficiency in all our heart failure patients In the PARADIGM-HF study a new agent in heart failure an angiotensin receptor neprilysin inhibitor known as LCZ 696 has been compared to enalapril in 8,399 patients The primary endpoint was the combined risk of cardiovascular death and hospitalisation for heart failure and LCZ reduced the risk of that endpoint by 20 per cent above and beyond enalapril with an extremely small p value Amazingly enough the new drug, LCZ696 had fewer side effects than the gold standard So fantastic news for heart failure. Starting from CONFIRM, we have an effect on quality of life, we have an effect on mobility, is that important? or do we just have to focus on prolonging life? What is important for a patient with heart failure? Would this change your practice? Very much so, we have got three amazing drugs in the form of ACE inhibitors, beta blockers and aldosterone antagonists That have revolutionised the management of heart failure, but despite this there are several symptomatic patients in whom the only way to treat is an increase in the dose of diuretics which is marred with hypotension and deterioration of renal function and therefore the understanding that 50 per cent of these individuals have iron deficiency and that treatment of this iron deficiency leads to a gain of 18 meters during a functional walk during six minutes is an amazing benefit it is the difference between someone being able to walk from their bedroom to the kitchen to make a cup or tea versus someone being unable to do that I think that is an important point: I want to stress that we’re not treating anaemia here, we are treating iron deficiency What could be the mechanism? Why is it important to treat iron deficiency in heart failure patients? Frank? Well first of all, you both answer right it’s a wonderful finding, it is clinically highly relevant and you wonder how did they – what’s the mechanism behind this Confirming some of the things that we knew already isn’t it? It is. That’s why the acronym was wisely picked It builds on the FAIR HF Study published in the New England Medical a couple of years ago led by Stefan Ankar, that was a 24 week follow up. CONFIRM HF is a year follow up I have to confess I’m a co-author of that, I’m a little biased towards that study It’s a wonderful finding But back to the mechanism that was, as you pointed out, irrespective of the anaemia and you wonder why that is, because iron is biologically so important, it’s a key metal co-factor: not only for haemoglobin but for myoglobin it’s for cytochromes, for other enzymes like catalases, you’d be interested in: So there is the biologic plausibility out there to test it and they did that, and that translated into a meaningful symptomatic benefit The challenge is now, does that translate into morbidity and mortality? So it set the stage for an outcome trial And does it change the screening practice? are we screening all heart failure patients for ferritin? Very important once again, progress came here by thinking outside of the box it’s not really something that you think first of as a cardiologist, is what is the iron status and this is irrespective of haemoglobin you remember first haemoglobin was 12 in that that’s pretty good actually But you look at ferritin, which is an acute phase protein, so if it’s low, below a 100, 10 to a 100, that’s fine, then you are depleted, you should do it in the range from 100 nanograms per millilitre to 300, look for the transferrin saturation, and then you can do it that’s how they did it and it’s an IV iron and it helped the patient I’m interested about, what type of patient this would work in? is this iron deficiency just a reflection on longer heart failure duration older age, co-morbidities, frailty? Heart failure is a disease of co-morbidities you are absolutely right, and that’s actually where all the idea came from the nephrologists have worked with that and they saw when they gave IV iron, renal function got better Are you giving it right now in your outpatient clinic? In which percentages of patients? I do give it, but we have to be careful with the guideline recommendations so far I have to stress this once again we have to curb our enthusiasm a bit here Exactly, we don’t have outcomes, hard outcomes We don’t have hard outcomes so we do not have a 1A recommendation yet it set the stage for an outcome trial but we do it because we have no alternative and as Sanjay said it’s very important that my patients who have symptoms have less symptoms The important thing is that you get a year’s benefit with just two injections in 75 per cent of patients That is a very good point So if we go now to the real thing, we have outcomes, we have symptoms, we have all that you may possibly want and that is the PARDIGM HF, we haven’t seen something like that for many, many, years, right? This is a great success! So where is this miracle coming from? what is the magic recipe? Good that you are so enthusiastic because I am, you know I’m a heart failure guy all my life and this really instilled a lot of enthusiasm in our field This has been 27 years after CONSENSUS when ACE inhibitors were introduced by Karl Swedberg and his team into clinical medicine it’s around the time I started cardiology That’s old it is already, imagine. Marl Swedberg was part of that PARADIGM trial as well And what they did now was spectacular: they challenged the champion, they challenged ACE inhibitors and they won! I have, and I ask you all, have you ever seen a trial with seven zero’s behind the comma? The p value to win on what you say, the real thing cardiovascular mortality, total mortality, hospitalisation whatever have you That’s fantastic, so it this is truly a paradigm change I think John McMurray and Milton Packer who designed the trial should also be applauded for picking that acronym Yes, they’ve been lucky I want to stress this lucky, because everybody thought omapatrilat, right? So it wasn’t exactly a ‘given’ that this would have worked without important side effects as happened before with the omapatrilat The clinical trial in the end is the Real McCoy: you have to do it All the good basic science you know so well Barbara ultimately needs to be tested in outcome trials, they did this so the question is, what is that? This drug is an ARNE – it’s nothing to do with Arnold Schwartzenegger It’s an angiotensin receptor antagonist valsartan, so we know what that is but the other one is an NINI, it’s a neprilisyn inhibitor, what is that? that’s an enzyme in the endothelium that blocks the degradation of vasoactive peptide some of them, which are vasoconstrictors and some of which are vasodilators and have a lot of the pleiotropic effect so that can turn out good or bad, so you don’t know so when we look at the result of the trial what we see a lot of the good stuff goes out, that’s good news and that’s probably what the mechanism is and that’s namely particularly natriuretic peptides BNP levels go up and dromedelin, so maybe there’s a mechanism I always say, translation medicine is not a one-way street, here we go back to basic science go back to clinical science, say: you explain to us now why it saves lives? That’s reverse translation you mean? It’s cross talk, I rather call it cross fertilisation But it is a spectacular finding and we have to see how we implement that in the guidelines now and first, this is not available yet regulatory authorities, I think have now doubt we should be cautious not too overly enthusiastic but now we have a spectacular finding like that I think that will come into the guidelines and that will be approved and available soon in Europe and on both sides of the Atlantic But, Frank, I think people at the back of their minds are still worried about angioedema you know, this clearly was there with omipatrilat Absolutely, but omipatrilat was part of that, an ACE inhibitor which impacts on bradykinin and in the breakdown of bradykinin, you have more bradykinin that makes angioedema and that is less the case with that ARNI because they replaced the ACE inhibitor with an ARB with valsartan This is a key point, you should not give it with an ACE inhibitor But don’t forget, in our guidelines we recommend an ACE inhibitor first and only if not tolerated you go to an ARB but here it’s an ARB, they put the ARB in here because they wanted to get rid of the angioedema risk and in the trial it looked very well tolerated but the only little bit we should be careful, whether that translates into long term safety, it needs to be shown, but I have no doubt that this will really revolutionize our practice I really think so I think this is true, it definitely will move the enalapril from number 1 in the list This congress will be remembered also for this trial Yes I think so So, this has been some fantastic news and it has been, as you said, something to remember not so positive have been the heart failure trials on vagal stimulation that is another beautiful hypothesis you affect the autonomic tone to the heart and this is going to be beneficial to be precise maybe most of the evidence is on sudden death rather than left ventricular remodelling so why do you think it didn’t work, Silvia? You’re absolutely right, first of all the most compelling evidence from the basic science is on the implication of the vagus tone and reflects this on sudden cardiac death reduction and this has not yet been addressed by the studies an important point is that we still are exploring how we want to do vagal stimulation we are still debating whether it’s left or right even if the ANTHEM, on small population, seems to show that they are equally equivalent and maybe also effective but the trial was not powered for that we are also still trying to understand the frequency of the stimulation that can affect the percentage of afferent versus efferent fibres that get activated now if we look at the NECTAR, which is a small study and also we should remember that so far we have seen only the result at 6 months and there will be a follow up at 18 so we might get more but the study raises the point that we don’t know in fact if the vagal stimulation was actively working there is no reduction in heart rate in these patients And it serves us once again as a reminder, do the adequately powered large scale outcome trials in devices as well why should they be differently handled than drugs? you can be pleasantly surprised as in PARADIGM but you can often not and we’ll talk about that certainly later it can go the other way you have to test them, challenge them whether it’s really mean something clinically relevant In this case don’t you think that they should also consider having a biomarker to actually demonstrate as a mid term that the device is actually working. That comes with it, you want to understand why you do something good or bad, you’re right but — ultimately — patents have to live better and longer with it The problem is that as for this, as for renal denervation which we will deal with later, there is really no intermediate read-out. What is the read-out about that the device is working, doing what is written on the box? If at the end you find out that heart rate variability has not been modified and then — as in this trial — 10 devices out of almost 100 didn’t work at all because they had some failure you wonder if we had really tested here the concept and the proposition that we had for the trial, so I would wait and see It makes a nice change, this is the first time in heart failure for a while that a tablet is winning over a device So Barbara, I thing that people want to know what is the take home message from this and for me, as a non heart failure doctor, the issue is that both CONFIRM in its impact on symptoms and quality of life and PARADIGM HF are really going to have an impact and if we thought a couple of month back that a patient coming into and outpatient clinic who appeared to be stable, comfortable with class II level of symptoms and heart failure on the best standard of care that we knew at the time that reduced mortality, that we could have another 20 per cent reduction in cardiovascular mortality and hospitalisation we would have been amazed. So, this is a game changer. Yes and especially because we’re substituting with another drug rather than adding to an existing medication So we’ve a whole lot of new guidelines in this congress let’s see what’s happening Essential tools for your practice, stand by for the new ESC Guidelines That’s a joint guidelines that were developed together between surgeons and cardiologists If we compare with the 2010 guidelines, in these guidelines for patients with left anterior descending LAD disease for both PCI and CAGB, we provide a class 1 recommendation The objectives for developing new guidelines now was the fact that we have new evidence on risk stratification of pulmonary embolism, so risk categories and we had, of course, in the meantime, a lot of new evidence on the treatment of the disease particularly anticoagulation which is a contemporary topic also reperfusion strategies and we had thirdly new evidence on sequelae of pulmonary embolism such as chronic thrombi embolic pulmonary hypertension We have to consider the aorta as a full organ and the division between the abdominal and thoracic is somehow artificial and there are many patients who can have lesions on both sides so take the aorta as a full organ and also when you go to consider the imaging methods you also have to balance the benefits and the risks specifically in younger patients we have to think about the radiation issues and finally regarding the treatment endovascular therapy has really well developed and pushed the surgery a bit in the specific boundaries Those guidelines include management of adults and children with hypertrophic cardiomyopathy they also include hypertrophic cardiomyopathy caused by specific diseases, as amyloidosis, or Fabry disease for example It also proposes a base for genetic counselling and genetic testing and finally it also proposes an algorithm to calculate the risk of sudden cardiac death at five years So several new guidelines, guidelines that are important for practice, but we don’t have the time to discuss them all we’re going to focus mainly on the hypertrophic cardiomyopathy guidelines So, Sanjay, tell us, what do these do for you? They’re highly relevant and they’re timely Hypertrophic cardiomyopathy is most recognized or should I say feared, for its association with arrhythmogenic sudden cardiac death in adolescents and young adults exercise is a trigger for sudden death and hypertrophic cardiomyopathy is the commonest cause of sudden cardiac death in young athletes now amongst some of the clinical challenges in hypertrophic cardiomyopathy is the distinction between physiological left ventricular hypertrophy of athletes and morphologically mild hypertrophic cardiomyopathy as well as the prediction of sudden cardiac death in all affected individuals In this regard, the recommendations are really pertinent because they discuss the role of multimodality imaging and adjunctive ECG in the differentiation between sarcomeric contractile mutation induced hypertrophic cardiomyopathy and other phenocopies and, most importantly for me they introduce a novel risk calculator for sudden cardiac death based on syncope, a family history of sudden death various echocardiographic parameters and the presence or absence of non-sustained ventricular tachycardia Sanjay, thank you I think that’s really important and taking up the topic of this risk calculator the first time we’ve seen this tell us about it, Silvia? Yes, I think that behind the calculator there is a very dramatic change in our re-stratification process we will go from using one parameter enough sufficient to say the patient has high risk and we don’t put a number to that risk to have in now this calculator that use multi parameters as Sanjay summarized and give us a number that is the five year risk percentage So, I think it will allow us to get a much more complete sense of the risk of the patient and therefore the availability of this calculator on-line will really allow everyone to use it and apply in his own practice But, do not use it in a blind way because within the whole group there are people for example with amyloid Absolutely, I think that we have to keep in mind that it was merely developed on the patients with genetic form of cardiomyopathy and specifically the sarcomeric that are the most common forms within the genetic part Thank you, now Sanjay touched on the role of imaging, multimodality imaging, clearly important Genevieve, what do you think? It’s a clearly important point this is a perfect example these guidelines on hypertrophic cardiomyopathy are a perfect example of the integration of the different imaging modalities in how to take care of these patients and I would like highlight that first of all echo has received a class 1 recommendation for the diagnosis of hypertrophic cardiomyopathy for the early diagnosis in the relatives that have not yet develop any hypertrophic pattern with the first time, we have a use of deformation imaging coming in this recommendation the second point is that the imaging may help in the assessment of prognosis as has been pointed out with the use of the thickness of the left ventricle wall and the size of the left atrium and, at least, we have also the aetiology that may be helped by imaging with the integration of echo first with several signs but also interestingly with MRI and also nuclear imaging with a transgenerating diagnosis, so I think it’s fine I think we need to go to the guideline to see the detail in that This is why most of cardiologists are aware about the improvements in in cardiac imaging these guidelines also stress the fact that also vascular imaging has made great improvement notably CT angio, also MRI angio and, aortic diseases guidelines really stress the value of those imaging modalities in diagnosing, management and long-term follow up of these patients And regarding these guidelines, they also highlight the fact that among all these imaging modalities, we should use the ones that is the less, the better for the patients in terms of reduction of radiation so that’s a very important point also Radiation is important but, competence is also important so, you have to work with the imaging modality that is also familiar in your institution May I also come back on this magic number of the risk score, how much, because this number will eventually determine who is going to get an ICD so, how much evidence there is behind those cut-off points and what will be the implication on ICD implantation in Europe? That is a very important point in fact, we have to keep separate the numbers that estimated and quantify the risk and the use we make of these numbers so, behind the numbers there are 3,000 patients so, I would say it’s a pretty robust population so, I’m pretty confident, my problem is not is it correct that the risk of that population is truly 6 per cent in 5 years or whatever the numbers but it is the fact that the recommendation then translates who should get a defibrillator and say that if the risk is higher than 6 per cent in five years, there is a class 2A recommendation there is where you’re perfectly right It means that we consider that everyone with one per cent per annum of mortality should get an ICD, that could be a very high number so, we need to be very careful the number we don’t have is in an average population of patients with hypertrophic cardiomyopathy how many have more than 6 per cent? that’s something to count So, we can’t leave this segment without talking about the revascularisation guideline because clearly this is important for the practice for huge number of people, Marco, what are your thoughts on this? The first thought is that it’s important to underscore that these guidelines were a joint position from the European Society of Cardiology and European Association of Cardiothoracic Surgeons They’re once again talking to each other! Yes, talking to each other and really stressing the value of the heart team. Now if you want to look what are the new aspect of those guidelines, we can say that with respect to revascularisation modality, PCR or CABG now PCR has become a class 1 indication for one or two left vessel disease with inclusion of the proximal LAD and also, being a class 1 indication for ostial left main stenosis in the presence of simple disease Again, these guidelines stresses the fact for diabetic patients, with stable disease, and multi-vessel involvement surgery remain the treatment of choice So, key messages there, thank you for that In this congress, there’ve been really important major trials in the field of coronary artery disease and lipids let’s see… In CAD, lower might, or might not, be better Alirocumab is a new lipid lowering agent, a fully human monoclonal antibody for which four trials in the ODYSSEY series Combo II, FH 1 and 2 and ODYSSEY Long Term were reported in an ESC Hotline session What we’ve seen across the different studies is that this treatment of a sub-cutaneous injection given for a year works, it’s well tolerated and produces 50 to 60 per cent, depending on the dosing, reductions in LDL cholesterol but it gives us great encouragement that these dramatic reductions in LDL will translate into reductions in cardiovascular events The large randomised SIGNIFY study was designed to evaluate the impact of heart rate reduction by ivabradine in patients with stable coronary artery disease without clinical heart failure We found that reducing the heart rate with ivabradine, using a high dose of ivabradine and effectively reducing the heart rate we had no effect in terms of cardiovascular death and non-fatal myocardial infarction We had specifically expected to find a beneficial result in the patients with angina, and to our surprise what we found was an increased incidence of the primary endpoint, that’s cardiovascular death, non fatal myocardial infarction in the patients with angina There’s one definite conclusion and that is that lowering heart rate in patients with coronary artery disease and without heart failure does not improve outcome, does not prevent the progression of coronary artery disease you cannot do that by lowering heart rate Keith, it’s all about PCSK9 and so PCSK9 is not a super-statin It’s something completely different that binds to the LDL receptor and leads to its proteolysis and destruction so once we have a PCSK9 inhibitor we increase the LDL receptors and we decrease the LDL cholesterol but what it is good is that you would expect Ok, well, you have the same with statins would it work with statins? It does, it works on top of statins because the statins would up-regulate PCSK9 so, there is a synergism, a big effect So, inject it every two weeks? Yes, this is the problem Sanjay, are you happy, for instance, in your practice to consider an antibody that is injected once every two week, for 2 weeks but that lowers the cholesterol as much, at least as much as a high potency statin? and we should mention that there are others on the horizon that are maybe once a month? Well to answer your question, Barbara subcutaneous injections aren’t novel people with diabetes are injecting themselves and people with renal failure get injected with erythropoietin What we’re talking about here is a massive reduction in LDL cholesterol if one considers that people with hypercholesterolemia don’t achieve LDL targets in 80 per cent of cases and post-STEMI, we can not achieve targets in up to 60 per cent of individuals these studies show a 50 per cent reduction in LDL cholesterol and 70 to 80 per cent of individuals achieving targets I can only see a good thing of course, one has to wait for long term trials to see how these translate into overall cardiovascular morbidity and mortality And also to decide which is the population to use these in, clearly people with for example heterozygous FH, that is a clear problem population and some of the people with persistent hyperlipidemia despite maximal statins But, I think defining the population’s still is going tho be challenging isn’t it? I think so, I would say that we know there is a direct correlation between LDL cholesterol concentration and cardiovascular events, here we’ve got a drug that brings down your cholesterol, the LDL concentration by 2 millimoles, which is practically as good as plasmapheresis really I think, we have to await long term studies before getting too excited but I think the potential is there So, this tells us the mechanism works that potentially exciting, the magnitude is substantial but we do need large outcome trials to be definitive is that fair? I think it is fair, but I think there is a ray of hope in this preliminary, in the long term of the ODYSSEY trials, showing really that there is a signal on events as well On the separation of the curves, already as you would expect with a reduction in LDL cholesterol by 2 millimoles as you said, so it’s a dramatic reduction I would say that it’s going to be the drug of choice for familiar hypercholesterolemia for sure and also in anyone with an ESC score of more than 10 per cent I suspect So, it’s not going to supplant statin we have a lot of data on that, on efficacy on safety, but it works on top of it which I think very comforting So not everything is going well though Not everything is going well with lipids another important hypothesis was tested and that was whether LPPLA2, in the systemic circulation by lowering that, we could change inflammation and change susceptibility to future events and that was tested in a very large trial the SOLID-TIMI 52 trial, and you couldn’t get closer to zero impact, the lines were superimposed So what does it tell us? I think it tells us that the hypothesis in relation to systemic levels has not had an impact, we still don’t know whether it’s the systemic levels as markers of inflammation or whether it’s in plaque, what do you think, Barbara? I think there’s a lot of positive association between inflammation and events but whether that’s important or a crucial step on causality remains to be assessed properly and the trial with methotrexate — will address that Do you believe that inflammation is, that there is evidence that is a causal factor on coronary events? I think we simply do not know yet there’s one big challenge with basic science here we do not have animal models that mimic plaque rupture in man and so it’s very hard to predict what the clinical read-out will be along the line that’s a real tough one and you have to ultimately do the big trials but now, to tell us that inflammation theory is dead I think that’s too premature It’s just that that factor didn’t work out to be of that clinically relevant as we previously thought We will know soon, people are embracing this hypothesis whole heartedly and so then we will have, with these trials, the answer to this hypothesis which is still very dear to my heart I really hope that it will work! I think we shouldn’t let people going away from this think that the inflammation hypothesis is necessarily wrong, you know It’s still not tested completely So the other problem if you like regarding hypothesis and what we do with them is SIGNIFY, the result of SIGNIFY, so is the heart rate a problem, the wrong target in this population? that’s the last line of Pr Kim Fox, it says well maybe heart rate is not something we should focus on in patients with coronary artery disease and I immediately think, well, if you lower the heart rate with a beta blocker you’re doing quite well so is there something wrong with lowering the heart rate? or is it too much? I think we’ve got to think about the context because we know in heart failure that ivabradine was successful in that setting but this is a different setting this is testing a different hypothesis in stable angina and you know, as Kim Fox also presented there was clearly a signal that individuals with symptoms of ischaemia did worse, and that was unexpected so for me it says, lowering heart rate this way, by this amount didn’t work, but I don’t know yet whether that is absolutely convincing whether there may be other ways of doing it The clarification of things is very important because we have a long story of mistakes driven by trying to target surrogate end points, but sometimes surrogate endpoints are just a signal of something else and probably heart rate doesn’t mean the same or may not have the same causal mechanisms in heart failure as in coronary artery disease so heart rate in heart failure may actually be the signal of high activation of the hormonal system while it may not be the same in patients, stable patients, with coronary artery disease so it is not that lowering heart rate doesn’t work, it is that it may be different settings It may be actually that lowering with different drugs makes a difference, we know that from heart failure example, that it is not beta blockers the same as diltiazim or verapamil and also, it may be actually that they was too high, the dose of the drug so there are many hypotheses still to be tested so I don’t think research in this thing is finished at all I think that we need to be careful in driving any conclusions with decrease or not decrease of heart rate in these patients, in CAD patients, because clearly we may hypothesise that those who suffered from adverse events, with really low, low, heart rate, and we don’t yet get this information so we need to wait for this information and the potential relationship between the degree of adverse events and the degree of heart rate reduction and this is something which is quite important to get, and we cannot avoid the hypothesis of a J curve for the heart rate so, I think it’s a little bit too early to say that decreasing heart rate in patients with CAD is not a marker of outcome for the future I’m not quite sure I fully concur with that, because there were probably a little too ambitious, they doubled the dose they started with a heart rate of 70, went down 10 to 60, in that patient population that means in some well below 55 and up to 50 there was 700 patients with symptomatic bradycardia in there so that tells you there were probably too ambitious and I think was a sign for a J curve there and we know that, and I think that was too low because when you look at heart failure where in SHIFT for example, they had a beautiful result in ischaemic and patients with non ischaemic cardiomyopathy alike so once again, people should clearly understand now this was a different population in heart failure it’s a good drug, it’s safe, it has been tested, it’s in the guidelines and I will continue using it in heart failure patients who are with a heart rate well above 70 So, Frank, a key message, that people shouldn’t go away thinking that in heart failure they’ve got to take their patients off this drug Absolutely not, you’re right, because once again in SHIFT when you looked at the ischaemics and the non ischaemics they all benefited from the drug but don’t go too low way beyond 60, below 60 is probably too ambitious And I still have a worry at the back of my mind about the patient with heart failure and coronary artery disease and we need more information Absolutely, we should be cautious and we should individualized treatment So really, there’s been important new studies in the field of myocardial infarction, so let’s see some of these How fast and how complete should we be? TRAPID-AMI, a prospective international study reported in the first ESC 2014 Registry Hot line evaluated the efficacy of a 1 hour algorithm for diagnosing myocardial infarction using high sensitivity cardiac troponin T The application of the 1 hour high sensitivity cardiac troponin T algorithm is very efficacious, 75 per cent of patients can really be assigned rule out or rule in the algorithm is safe because the negative predictive value is very high it is safe because all patients receive long term follow-up and the rate of mortality in those patients assigned rule out was extremely low In CvLPRIT, 296 patients with heart attacks from 7 UK centres were randomised to either revascularisation of the infarct related artery only or to have complete revascularisation to include also all other arteries found to be occluded We found that there was a hazard ratio of of 0.45, a 55 per cent reduction in the overall MACE at 12 months It mirrors what was found in PRAMI a year ago and supports some of the findings of PRAMI and tells us that maybe we should at least be thinking about treating the patients for complete revascularisation during their index admission In the ATLANTIC study, 1,862 patients with STEMI were randomized to receive treatment with ticagrelor as well as aspirin and standard care either in the ambulance or in hospital The conclusions are simple, there is no safety issue with an early administration of ticagrelor and you will not improve probably coronary perfusion at the time of PCI but, after PCI you may reduce the ischaemic complications of primary PCI such as stent thrombosis, so for drugs that we want to use anyway in this type of patient it will make sense now to say use it as early as possible So the TRAPID-MI study looked at the possibility of very early rule out, 1 hour rule out with high sensitivity troponin. Hector, tell me about this This is a very exciting news compare with the previous algorithm that we had in the ESC guidelines 2 or 3 years ago, there’s 2 news First, the first algorithm was in 3 hours, now they’ve moved to 1 hour the second difference is that actually we have a specific cut off points before, we didn’t even know what was the increase in troponin to make the distinction of myocardial infarction Now, in this study, we have a clear cut off point that at 1 hour we can rule out 66 per cent versus 63 per cent of the patients for myocardial infarction, not having myocardial infarction And importantly, they had the follow up to show there were extremely low risk Well, that is so reassuring, so the negative predictive value was 99 per cent, that is amazing The most important bit of this study, do you think? Absolutely, this would have an amazing impact in emergency departments just narrowing the time when you can rule out and discharge patients with such a short time, it’s amazingly powerful You’re enthusiastic, but do we need a randomized trial to validate this? Well, I’m enthusiastic about this possibility I would say that not everything is closed this was an observational study, the decisions were not made based on this algorithm the patients who actually had a diagnosis of myocardial infarction were treated at the discretion of the different centres, so I think that would be more comfortable if it had confirmation in which there’s a real management of the patient driven by this algorithm So, this was observational, important and great potential, but it didn’t drive management change Marco, what do you think? I think that these data are really impressive, nevertheless they need confirmation and so, so far, the 2011 guidelines of the ESC recommend the 3 hours algorithm for a second measurement of troponin so, I would suggest to stick with it and wait for the next guideline of the non STEMI that will be presented next year in London and see whether or not this new algorithm will be incorporated Ok, that’s very helpful and you know, in some parts of the world CT is used as part of this early rule-out process Genevieve, should people be using CT in that setting? Yes, to rule out CAD in those patients, it’s part of the recommendation that were issued last year but I will also address the fact that it’s important to rule out other aetiology and that echocardiography is very easy to perform in the emergency room and that can give you very easily data on potential segmental abnormalities but also other disease so that’s another point to be considered I would d like to go back to the CT issue because the value of CT in several randomised trials, was mainly the reduction, the rule out the reduction of time in the emergency room and actually those trials were not performed in a setting where high sensitivity troponin was available so, it’s completely unknown whether the CT may add something on top of high sensitivity troponin and with such a wonderful negative predictive value that Hector was telling us I mean, the value of CT, for me, may become marginal in this setting But I think that this is really re-shaping the landscape in the field because there’s still 22 per cent who are not ruled in or ruled out what to do with these patients is not really known so, maybe there’s room for imaging, more biomarkers and definitely, I would say that we need to review the chest pain unit theory all over the role of these biomarkers, timing, imaging, and so on But even, before we work out the theory, there is a logistic problem all of our emergency departments, is to how to deal with this large number of people early on, so it’s addressing that important question So lets now turn to the CvLPRIT trial so the CvLPRIT trial was looking at the role of either the infarct-artery related lesion and dealing with that or, during hospitalisation, dealing with the other key lesions but, they didn’t do it all at once they did some early on, mostly, and some staged so, and it’s not a huge trial Marco, how do we take this? So, there are 2 issues number 1, is complete revascularisation versus incomplete revascularisation, number 2 is the timing and so, CvLPRIT, similar as PRAMI, looked into immediate, because also in CvLPRIT most of the patients were treated with immediate full revascularisation versus medical management actually, for most of the physicians, a more relevant question is what is the role of staged revascularisation for patients presenting with STEMI and multi-vessel disease and actually, this question will be answered in a large scale randomised clinical trial powered for clinical event namely the COMPLETE trial, will really look what is the value of stage myocardial revascularisation in STEMI patients with multivessel disease compared with medical management of non-infarct related arteries So, that question hasn’t been addressed, but in fairness to the investigators what they were addressing, is whether more complete revascularisation at sometime during the hospitalisation is better than just the infarct artery and it’s fairly consistent with the PRAMI data, isn’t it? Indeed, but this is a small trial, 300 patient trial and the other important thing is that we have to realise that this issue is difficult to study because, if we have a trial comparing immediate full revascularisation versus staged, for example, then we know that if we perform two procedures most of the events are pre-procedural myocardial infarction but obviously, if you treat one patient in the acute phase and you don’t have a fatal event from the non-culprit arteries, then even if you have a diagonal obstruction, this will not count as an event so, from the methodological point of view, this is quite a complex issue So, wait and see for the big trials, or do you disagree Hector? No, I don’t disagree, but I think we have to be very careful in not extrapolating these two trials to lead to the conclusion that actually all vessels should be treated immediately in primary PCI I think that we’re far away from getting the evidence for that and for instance, if you’re late at night and you’ve had a long day and you have a small MI, you treat the patient, he seems stable and then, you have 2 complex lesions do you really want to do that at 2 o’clock in the morning or it’s better to wait for one or two days? But what we are all saying, is the issue of staged versus immediate has not been addressed yet That needs to be clear, so another important trial that we’ve seen was the use of ticagrelor in the ambulance in the ATLANTIC trial and we’ve heard from Gilles Montalescot that he kind of favours the pre-treatment is that all our interpretation? So, I would say that actually this is clearly a negative trial and we have a clear explanation for that because Gilles and co-workers made also a subgroup a sub-study with pharmacodynamic data showing that at no time point there was a difference in platelet aggregation inhibition between treatment in the pre-hospital phase versus in the cath-lab so, it’s not unexpected that actually there was no improvement in the reperfusion at the time of PCI. While Gilles Montalsecot said there may be a benefit in stent thrombosis, this is true and stent thrombosis was a secondary endpoint of the trial nevertheless, we could also say that in terms of mortality the trend was in the other direction and overall, there was no difference in MACE and, once more, the study was not powered to look at MACE but clearly, this additional piece of information questions the value of pre-treatment in acute coronary syndrome, that was already challenged last year at the ESC by the publication of the the ACCOAST study in non-STEMI patients So, I think that’s really put it very clearly in context you are happy with this those conclusions, Hector? Yes, I think it was a mechanistic study, so changing practice by mechanistic study and in particular by a negative study is nonsense, so no changes in practices are warranted but, they’re STEMI networks that are already doing this and some others treat in the hospital, so… But, in fairness to the investigators what they’ve established is that there is no net harm from doing that So, everyone is going to be reassured about what they’re doing To take the point of Hector, for the time being, there is no data that pre-treating patients with any agent in STEMI may be beneficial Even aspirin? Even more potent agents, aspirin, good point But even with more potent agents, IV Gp2b3a receptor inhibitors were disappointing in this setting So, pretreatment has been disappointing Ok, so what were going to do is to see some snap shots of some other important presentations during the congress let’s see the snapshots… Smartphones, tablets, remote devices, technology is everywhere in cardiology I think cardiology practice is undergoing a revolution, E-health is here, it’s getting stronger and stronger and mobile health particularly is something that’s going to greatly change in the next 5 years The politicians are very enthusiastic about technology introduction and think it will save money I’m not so convinced it will save money, but it means that we can do more, and more efficiently with the same work-force Where did renal denervation for hypertension stand in 2014 during the ESC 7 years after its initial clinical promise and 4 months after the negative results of SYMPLICITY III… The main messages coming out of this synthesis of the denervation story thus far, are that there are technical issues still to be sorted that denervation remains viable in appropriate patients If appropriately conducted and most importantly that if we appropriately and aggressively treat our patients before we get to denervation many won ‘t need it In the X-VeRT trial, 1,504 patients with atrial fibrillation scheduled for early or delayed cardioversion, were randomised to have either vitamin K antagonist therapy or rivaroxaban 20mg daily The incidence of primary efficacy was very low in both arms, 0.51 per cent in the rivaroxaban arm and 1.02 in the VKA arm The incidence of bleeding events, the principle safety endpoint was also very low and similar in the 2 study arms Patients requiring delayed cardioversion those who were assigned to rivaroxaban presented with a significantly shorter time to cardioversion 22 days, versus patients in the VKA group, 32 days 1,400 patients with tuberculosis related pericarditis from 9 African countries were randomised to receive either corticosteroid therapy or placebo together with their anti tuberculosis treatment The use of steroids or mycobacterium W does not make a difference to death, combined with tamponade or constriction however, for the practicing clinician the take home message is that, number 1, steroids ought to be used selectively in patients with TB pericarditis They ought to be avoided in those who are HIV positive because of the increased chances of cancer and they may be used in those who are HIV negative because of the chances of reducing constriction and hospitalisation Sanjay, very attractive the idea of E-health It empowers the patients, they are monitored in their own home they know what they have Would that affect maybe the compliance to treatment in patients on long term treatment would be motivated? It may not save money but it makes money indirectly It’s got to be the way forward Is that for the patient or for the doctor? For both, doctors and patients We’ve got to a situation where we project that 1.7 billion people worldwide will be using smartphone health apps and these health apps, simple ones, will be able to monitor, and they are doing already heart rate, blood pressure, blood sugar, life style… and they’ve been useful in things like smoking cessation, in helping tailor treatments in important situations, such as heart failure to give you some example, there are about 100 thousand free apps available to us at the moment and the top 20 have been downloaded 230 million times already so, there is certainly an appetite for that in the way of changing the way we practice and particularly as we’re all getting older and the patients are getting older this will be the most comfortable way to have to be monitored But, we’ve got to remember that apps don’t just appear out there they actually have to be certified now and they have to have a CE mark on them So, you know, there is a sort of a quality control step there are not just in somebody back yard There is this issue of liability, of course They have been embraced by nations as well as all aspects of the clinical care, I’m optimistic on this one But Keith, you were asking about how they’ll help the physician they will reduce physicians time by 30 per cent just to give you some idea of detection of arrhythmias we rely on multiple 24 hours tapes and implanting invasive devices such as ‘reveal’ devices when an individual could actually e-mail you his rhythm when he was symptomatic I’m not sure it’s going to reduce our work load, actually, it could be the opposite it is going to be growing, probably it is going to be a different way of working but I’m not sure about reducing costs and I’m not sure about reducing work load So, there has to be a way of triaging all of this information One could argue paradoxically that they would be very useful in prevention and reduce the number of people that need to enter the hospital in the first place I am a little bit less optimistic about renal denervation, Frank so, is it the technique that doesn’t work or is it the sympathetic denervation that doesn’t work or we’re just focused on the wrong type of patients? Or it’s not done right Can I tick all of the above? I think Henry put it perfectly right It’s not the end, it’s rather the end of the beginning Probably, it’s a good thing that SYMPLICITY III curbed the enthusiasm a bit we have to do our homework now, again treat them with drugs adequately ACE inhibitors, calcium antagonists, diuretics. Spiro does the job beautifully in most patients and then we have to learn more about the technique we didn’t even know was the procedure effective So we have to learn more and I think we’ll learn more, there are new catheters coming new balloons and whatever with which you can apply the therapy and we have to learn and they have to do the outcome trials once again a reminder, devices, novel technologies have to be rigorously tested as drugs as well This is true, but let’s say, let’s empower the patient and say: we know the drugs work beautifully if the patients takes them some patients don’t want to take the drugs so why not recruit these patients and give them the option, do you want to… Dangerous road you’re taking Barbara! In non compliant patient, you offer an invasive strategy… You can do that, do the trial, but I personally think that is not the way to go forward first To now go for those who don’t want to take drugs and then offer them a therapy, I think we have to prove it in the patients, as we have started in resistant hypertension, it was fair enough or in others who qualify for drug therapy but for those who don’t want to take drugs, to do an invasive costly procedure with side effects and safety issues… I completely agree, first of all, we have to demonstrate that it works where the indication is clear then we can go after surrogate markers or other indications I think that the group of patients who have resistant hypertension is not a heterogeneous group there is a lot of secondary hypertension in the resistant hypertension, so it is not always easy It’s not going to be like supra ventricular tachycardia ablation where there is only sport you can just burn hypertension is much more complex, there are many mechanisms it is unlikely that patients will be totally controlled with a drug, that is not realistic We do know from the reference arm of SYMPLICITY III that when these people were systematically treated with appropriate medication they responded remarkably so this is the point from Barbara, that actually the size of the truly resistant population may be much smaller that we thought But they are still exposed to a high risk because they don’t take their tablets So, pragmatically, it would seem a logical choice, to give the choice to the patient Ok, one of the other studies that we saw was the XvERT study and the XvERT study was about cardioversion in people with atrial fibrillation on a new oral anticoagulant and this was a study of 1,500 patients and interestingly, the presenter said well, we need 15,000 to be sure of a difference in outcome, so Silvia how should we interpret this? The study was on purposely powered to be an exploratory study so, one can question whether it is reasonable not to enrol the amount of patients needed but if we think that this is not the end of the evidence, I think it’s an important evidence so, as long as we remember that this trial is not conclusively proven safety and efficacy, I think it’s important that it shows that there is definitely no excess of events in the patients treated with oral anticoagulants versus the conventional VKA agent and also the fact that the time for programmed defibrillation was something that was shorter makes them very appealing So, it’s addressing a potentially important clinical question because only 36 per cent of the patients in the VKA arm got their cardioversion within 56 days so, that really says something about it being very frustrating to get these people cardioverted in the delayed group I think that there is a concept there that we could gain and make our practice more convenient for the patients whether this is conclusively proven, I don’t think so but maybe you know registries to follow as this is being used more and more But nevertheless, we know already in some guidelines there are data in relation to dabigatran and also apixaban based on the limited evidence that there is out there Moreover, those drugs having already been approved to be used so it is a piece of evidence that reassures a little bit, definitely it is not the final question, but it is something that is helpful We will encounter more and more patients who are already on oral anticoagulants so that will also change the question as we go You are touching on the issue of large scale registries as important bits of information there have been important registries presented in this congress Genevieve, we’re thinking about the registry in prosthetic valve disease in pregnancy no single investigator can get the experience? So, that was a huge registry gathering data from pregnancy in women with valve disease and what is quite important to highlight is the great number of events occurring in women with mechanical prosthetic valves and the sad news is that these event affect not only the woman but also the baby and the other sad news is that no anticoagulant regimen has been proved superior to another one so, unfortunately we’re just facing this sad reality But, the registry shows that the tissue valves did substantially better Yes, I was speaking mainly about the mechanical prosthetic valves and to extend also this registry, there is another case where women are paying a very heavy tribute it is in the rheumatic heart disease and that was also another registry highlighting the presence of this rheumatic heart disease in many low or middle income countries and women are really affected at a young age and they are suffering the subsequent consequences since they have very poor access to contraception they have poor access to health care so, I thnk is something very important to take into account since we really need to display the message that we want all people treated with the optimal care, but unfortunately there are disparities in the countries So thinking about these registries and studies around the world there was a very impressive study that came from South Africa, the IMPI study IMPI stands for warrior, it is a Zulu tone for warrior, so what they were battling against is the really important worldwide problem of tuberculous pericarditis, we understand affecting maybe a million people and they were addressing the question of whether they could prevent constriction an interesting design, what do you think, Sanjay? As you say, a laudable study in a very large group of people with quiet severe tuberculous pericarditis complicated by large effusions as well These people were treated with prednisolone or a combination of prednisolone and immunotherapy and, it was a negative study overall but on the positive aspect, they prevented pericardio-constriction in individuals the sad thing was that 66 per cent of individuals were HIV positive and what this trial demonstrated was that in HIV positive patients it also demonstrated a higher prevalence of HIV linked malignancy and therefore, I would say that the take home message here is that in western countries and in developing countries, in HIV negative individuals such therapy may be acceptable in preventing pericardial constriction but we’ve got to be cautious with HIV positive patients more than cautious, but it is not clear whether it is the drugs, the steroids and the immunotherapy that actually cause the cancer or do they really unmask the process OK so, important trial, very carefully conducted trial you know, the first from Southern Africa, we hope to see more, that is important So, we’re coming to the closing moments of this session and, I don’t know Barbara if you’d like to go first in terms of your take home messages My take home message is to the pharmaceutical industry cardiovascular diseases is number one in the world, it has been confirmed this year it’s a global problem and we can still win there are big improvement still to be made so you should come back and invest in cardiovascular diseases, this is my take home message Excellent, Genevieve? Well, I would have a message to the health authorities across the world and also in the European countries to really tackle the disparities among the population regarding the healthcare I think that is an important message that the ESC has to deliver to our health authorities Terrific, Hector? I think, this congress brings excellent news for all the community working in acute cardiac care that acute myocardial infarction may be ruled out in just one hour in the emergency department Sanjay? Well, I’ve got a message for community as a whole PARADIGM and ODYSSEY, the future looks bright! Future looks bright, ok, Marco? I think we have to reconsider the value of pretreatment in acute coronary syndrome both in the STEMI population and also in patients presenting with non-ST segment elevation Silvia? My message is to agencies funding research that they should consider that what we have seen here in terms of new and exciting molecules and trials results come from the basic science we have seen new mechanisms of action new compounds, new pathways being explored, so basic science should be funded in cardiovascular Fantastic, Frank? Clearly, PARADIGM was for me THE highlight of the congress and instilled even more enthusiasm into the field I care most about, that’s heart failure taking centre stage And from my perspective, you know, we’re the ESC, but what we’ve seen is world-wide studies, key studies we’ve been talking about from South Africa, studies from China, studies from around the world that impact on our practice and this is really exciting because we’re learning from each other So Barbara, what are the take home messages for us at the end of this session? The take home message for all of us? What do we need to do next? What do we need to do next? We need to go to LONDON! We need to go to London Not to Oxford? But London is close enough I will see you in London London is an exciting city, one of the most exciting city in Europe So, finally a huge thank you to our panel of experts they have spent a lot of time going through all the information and carefully balancing this a huge thank you to Barbara who has been incredibly busy during this congress thank you to you for listening and thank you to the two sponsors of the programme see you in London Looking forward to welcoming you to London 2015 for a great congress See you in London

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