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dear colleagues, this is the role ofthe european society of cardiology to provide access to the mostimportant scientific information to all its members andto all its scientific community here in amsterdam, we hada tremendous congress and we have the opportunityto share with you top scientific data on behalf of the board of theeuropean society of cardiology i wish you a very warm welcometo this best of esc 2013 weel, here we are,i am keith fox

chairman of the program at the esccongress and i am delighted to welcome you to this live program what we are going to be doingis 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 excitingin terms of the future so, with me i want to begin byintroducing my co-chair barbara casadei, barbara is the chairof the highlights at the esc, welcome

and barbara, you are are going to beintroducing our panelists yes, we are same old keith and i,and i am delighted i am delighted to introduce abrand new international panel i start on my right genevieve derumeaux is from franceand she is our expert on imaging and then we have marco rossifrom switzerland who will comment on intervention sanjay sharma, who will commenton 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 programas well then we have frank ruschitzkawho will comment on hypertensionand heart failure and last but not least, peter clemmensenwho is our expert on acute cardiac coronary care thank you very muchgreat, thanks barbara, so we are going to start straight off with the first video clip of2 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 myocardialinfarction and to have had a successful

infarct artery pci they had to have multi-vessel diseasethey were randomized to 2 groups 1 group has immediatepreventive 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 anginaby 65 %

it indicates that preventive pciundertaken during the same procedures the infarct artery confers quite considerable benefitabout a two-third reduction in serious future cardiac events the taste trial, thrombus aspiration in st elevationmyocardial infarction was conducted in sweden, icelandand 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 stemirandomized to pci with or without thrombo aspiration the results on the primary endpoint of30 days mortality showed a neutral effect of the procedure 2.8 % in the thrombo aspirationgroup versus 3 % in the pci alone group so we have a very clear messagefrom 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 howactually do we interpret these we are going to start by discussingprami, 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 veryimportant point so the trial enrolment was planned to be600 patients and at the end was approximately under 450

so we have very little events at the endand is important to underscore the the strategy that was addressed what either pci of non culprit lesion at the time of acutestemi intervention or no procedure at all for the non culpritvessel, these may not be what most of the physicians clinicians would do,namely a stage procedure ok, so it's conservative againstdo it all at one stage rather than staged or even ischemiadriven

exactly, only 2 out of the 4 possible strategieswere investigated with this trial and is important to know thatthere is another much larger trial complete trial, which will enrollapproximately 4,000 patients addressing the same question,so i think the results are very important but i would describe ashypothesis generating ok, peter is that your interpretation? yes, i totally agree, but also i think we have toremember that this is challenging the current guidelines hasa iia indication to only concentrate on theculprit artery

so, i think this is very provocative to turn over the guidelines, we really,and both are saying, we need pretty robust evidence exactlyand there are other trials underway i would wait for the affirmative largertrials that are ongoing the complete and the premulti which ispart 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 tellokyou cannot push me further so barbara, let's discuss the next one taste, what a trial, what animaginative way of looking at registry using registry instead of justauditing practice but also doing something that is better and less expensive,a wonderful thing what i am puzzled is aboutthe results my colleagues are always showingpictures of all the garbage

that they aspirate it makes the cardiologist feel goodto take all that thing out why this does not help the patient? because, i think in the pastwe 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 asignal, when they looked retrospectively in the registry

they saw that thrombus aspirationwas not favorable to patient and then they tookthe 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 resultis unpredictable it's not always you really can predictwhether 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 excessof stroke has was shown by the previous meta-analysis yes, but this is still a little bitcounter-intuitive i would have thought that taking it out would have resulted inan 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 selectedpatient population remains open,also in this field there is another large scale trial ongoing, the total study approximatelythe same size but this is difficult for me to imaginethat this will overrule the result of the present studyso, here we have a study that is bigger than all of the othersthat 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 shouldwe will have

new issues,we will have to rewrite the guidelines for the next edition of the stemi guidelines so routine aspiration would not berecommended yes, in selected cases, it appears safewhich selected cases? well, i don't know because if youlook at the subgroup analysis they was no particular sub-groupthat benefit i was surprised that the right coronarythat has this big second segment, that usually those of usworking with angiography has a lot of thrombus

with no really side branches, and evenin the right coronary artery occlusions, no effect whatsoeverwait a second, what we've seen is 30-day outcomes when we first of all looked at thereperfusion 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 thingof the study is that we cannot say they were selected patient because 60 % of all patient that

presented with a stemi in swedenduring enrollment time of the study where included in the study,so really these are consecutive patients i think you have very strongly dataand routine thrombus aspiration cannot be recommendedbut the mortality is very low in those who were not randomizedthe 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 managedto 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 trialsmay be done in the future accoast randomized 4,333 patientsat the time of non st elevation acs diagnosisto either pre-treatment with prasugrel 30 milligrams orplacebo, 24 hours prior to going to the cathlab

actually, the results show thatthere is no benefit for pre-treatment, there is absolutely no difference in terms of outcomes betweenpre-treatment and no pre-treatment and there is a price to pay for thispre-treatment which is an excess of major bleeding, there was a 2 foldincrease 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 isactually something that is being done

routinely in many places pre-treatment, so here we havea large trial demonstrating no benefit at all, why, i think that in discussing this you have to appreciate that there mustbe 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 drugactually has kicked in and is already effective,so that i think explain the bleedsok, so you can imagine that maybe the treatment time

wasn't long enough to see benefit but this hazard, you think the hazardis the interaction between the prasugrel and the other agentsthat influence coagulation i speculate, because these patientswere also given heparin of course so, they were on a rather aggressive anticoagulant and antiplatelettreatment and got early intervention,we've seen that, this is way off, but we've seen in some trialsin the past that when you do very early

bypass surgeries on "hot" patients with acs that you might not have themost favorable outcome but the buzzing issue actually is thatbleeding was not so much observed in terms ofaccess related bleeding that somebody would expect, but also gi bleeding and other internal bleedingso these remains to be explained so, it is not access siteit is systemic bleeding this also support peter's point that itcould 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'tgive prasugrel up front but what do we if we are usingticagrelor well, i think there's a clear messagehere that has not been tested,but i think we should not change a strategy in patients with nonst presentations of acs but rather continue to pre-treat withticagrelor which was shown so clearly in the plato trial

to be beneficial so i think that wouldbe the strategy even if it didn't test pre-treatment versus on the tablei agree, it hasn't been tested, but it plays more into resonancewith the daily clinical practice that we see these days that these patients, who don't havest segment elevation when they come in usually, in most european country,even the most resourceful wait for a day, 2 day, 3 day beforetransfer to a cathlab i think if these patients were ina part of the world where they still use

clopidogrel and the patient been diagnosed on arrival should they wait untill they go to the cathlabor should they be treated on first diagnosis very provocative, with clopidogrel, whoknows, we don't have any data there's a recent meta-analysis that suggest thatalso with clopidogrel no huge benefit of giving a pre-treatmentbut even with ticagrelor so actually this study really challengesthe class i indication

for pre-treatment,but it remains open whether a longerpre-treatment time maybe beneficial, so this trial actuallydoes not reflect current clinical practice and actually the trial mandated coronary angiography within 24hours so the median loadingtime to angio was only 4 hours, wether another result would have beenappreciated with a longer delay remains open

marco, that's a great point becausei think you also have to appreciate that in this trial even the patient that went onto pci did not derive a benefit, this is what you wouldhave 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 besort of the sweet spot the ideal population, and even thatpopulation you didn't see

maybe the take-home message is that until ones doing the pci, when you needeffective 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 possiblyclopidogrel don't change thatthat 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 patientok, and so what should give them? nothingnothing at all? aspirin, anticoagulant, but no p2y12 inhibitor until they're in the cath labif 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, thesurgeon will like it we have got to be friends with our surgeons we will get so some data onpre-treatment with

ticagrelor in the ongoing atlantic trial but this is in stemi patients, sothis is not the same population it is a different cohortethey are younger may be less prone to bleeding because ofthe 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 allthe 4 guidelines that have been presented at the

congress but we will see some snapshotsthat we will then discussed later, so if we start with thevideo on guidelines the key word can be friendly, simplification, practical use in order to achieve this goal ofsimplification and to be really practical, we made theclassification based on ecg, namely the clinicalpresentation if you look at previous guidelines theywere 2 targets now the target systolic bloodpressure is 140 mmhg

for nearly all patients,for diastolic blood pressure the target is 90 mmhg exceptfor diabetic patients in whom the target is 85 mmhg there is something new with this table that we provide the physicianto evaluate the pretest probability,according to this probability, you go to the test and the test we have promotedis the stress imaging test the really hot messages is that therapy andmanagement of people with diabetes and

cardiovascular disease has to beindividualized involved in that is new individualizationfor 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 onpatients with atrial fibrillation has been not so clear,a bit mixed so pieces of new recommandations inthese guidelines, do you think is backed up by strong evidence? well, i think that you touch a very importantpoint and i think

that these guidelines are making an advancement in puting clearrecommendation on how to manage these patients even if we need to keep in mind thatthe randomized clinical trial, or more than one randomized clinical trial are not available so, one of the reason why atrial fibrillationassociated with heart failure as made a bit complicated to define the effectof crt seems to be related, and these guidelinesreally go in the detail to try to account for

that, and support that with evidencefrom the literature the fact that there is not completecapture of the biventricular pacing and that is really considernowadays key for influencing the outcome so, we are now saying in reading in theseguidelines that we need to be as close as possible to 100 %capture of the ventricle and these goes to the point thatthere is a recommendation for atrial nodal, av node ablation for ensuring thatthere is this very complete capturing

so the recommendation is a class 2a,it reflects the fact that there are no randomized clinical trialbut it points to the fact that we have several large studies thatsupporting this and in this respect is worthmentioning that the certify study led by maurizio gasperini is beingpresented at the esc, is a new study and the study really support thepoint that patients with heart failure permanent atrial fibrillation who are undergoing av junction or node ablation and crt have the same outcomethan sinus node patients

while the patients who have heart failure,atrial fibrillation and are taking medications to controlthe heart rate has almost twice the mortalityso, i think that this is an important point, that's direct in the direction of trying tofocus on these permanent pacing, effective pacing,and to go and think about av node ablationthis is almost too good to be true having patient with atrial fibrillationwho have the same prognosis of patients in sinus rhythm yes, i think that we need to back upwith

more robust evidence but this isencouraging considering how symptomatic these patients are and considering that they are at least25 % 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 therethese are highly symptomatic patients and one-quarter of our patients with heart failurehave atrial fibrillation during the course of their diseaseso there is enormous potential and i really don't understand why we haven't seen atrial that

we had some great acronyms for that,crt in afib i think that we should do thatand we heard with interest now your new approach of trials there is a need for an investigatorinitiated approach to address this issue because i want to have it up liftedfrom a 2a to a 1a because that is an invasive procedure,there is side effects you know these patients carry4, 5, 6 years of the course of their disease an implant with all the side effects and this is also costly, so i wouldrather based that on a 1a indication

based on a trial then on a 2a, they were good trialswe've seen, but there were not powered to really give us adefinite answer yet and the point is also that makinga person pacemaker dependent for life is a big decision, so it definitely deserve a strong evidencewe cannot afford not to have a trial on this so, staying on the guidelines and talkingabout the new guidelines on hypertension

there is a more conservative takes on thelevel of blood pressure we should achieve which would make a lot ofcardiologists 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 andsevere hypertension on dual therapy and my question will be well if we have already decidedthat they are at high-risk and a require a more aggressiveintervention why don't we throw

a statin as well and we stop this really costlystepwise approach in primary-care,can we afford it these days anyway? all excellent points, barbaraas i said several times before i am a football fan and i called ithypertension is coming home to cardiology and actually, we cardiologists werepushing 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 rightin a patient with cad these days are over thanksto the accord trial so, i am very happy with these more conservative,less aggressive guidelines just below 140 is perfectthe other point you made is also important, that ithink we now should start in patient with a stage iihypertension its totally appropriate to go for acombination therapy instead of going forwhat i call a sequential mono-therapy

and wasting unnecessary timeto get the blood pressure at targetyou are right, the question though is and there were a little be tooconservative 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 withnumbers, 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 bloodpressure 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 ipersonally thought that should be a stronger statement on thatin the guidelines but that's up to discussion i'm happy with blood pressure loweringfirst 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 denervationso there where follow-up data as this congress and they look as usual, fantastic and then there are ambulatory bloodpressure monitoring data they look not so exciting,right, maybe the kind of blood pressure reduction thatyou will see with one anti-hypertensive agent

and a lot of variability indicatingthat maybe there are a lot of non-responders so this is a technique that has beenembraced heartedly by the whole of europe and i was wondering does it pass the gramy test, would youdo it on your own grand-mother? well, it's a question whether i willjust do it in my mother-in-law no, i hear you but seriously, it is somewhere betweenhope and hype but what silvia said before,you know with atrial fibrillation

in crt, we need the trialsand just lowering the blood pressure is not enough we have to move from the numbers tooutcomes, i want to see that my patient on renal denervationwith resistant hypertension lives longer and better with itand we're not there yet, these trials are coming untill then, it's somewhere between hopeand hype but i agree with you,we also should treat our patients with resistanthypertension 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 apromising therapy, that's what it is they take the drugs, and there is no waythat this patient was called non-compliant, well we rather cure youwith the renal denervation

because we lower blood pressurebut 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 mantrai learned from this congress, trials we need more trials but they are on going trials in this fieldof course, they are simplicity 3 but, we have a lot of off-label use now and wehave to be cautious otherwise we will killed this very promisingtherapy, 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 stablecoronary artery disease now may be not as dramatic as the denervation, but how oneinvestigates the patient with suspected stable coronary disease, reallyimportant genevieve, the guidelines have downgraded the old approaches,what should people do? well, this is a very interesting point inthese guidelines with the weight put

on the pretest probability and this isquite important new to adress the potential test in the patient with intermediate pretest probability, so this is the firstpoint to be aware then the imaging community will beprobably happy to know that, even if the exercise test still remains anoption it should be preferred, and this is clearlyannounced like that in the guidelines to use the imaging test and this is avery important point also which is

addressed in these guidelines is to take care of radiation using this imaging test, so this is quiteimportant especially when you're dealing withyoung people so imaging test and reducing radiation another interesting point alsofor the imaging community is that for the first time appears inthe guidelines for detection of coronary arterydisease new technologies such as tissue dopplerimaging and stream

imaging in order to a unmask subtle abnormalities that you cannot assess when you'relooking at regional myocardial function so this is also an important information sanjay, you're an expert in athletes, in exercise, in all theseaspects, you evaluate a lot of people where there is maybe a query about coronary arterydisease what's your interpretation of how weshould go? well, i believe that people who are at low risk or have a pretest probability between 10 and 21 %

should probably undergo a ctcoronary calcium score it's a great rule out test andwith advances in radiation, we demonstrated that it's minimal,the amount of radiation received and it obviates the need foranti-platelet agents and statins, so my take-home messageis that if the calcium score is 0 that is the end of the story in low-risk patients and of coursethe problem is that once you have calcium in the coronary arteries we go back to the same strategy that isimaging, stress imagingand genevieve, say something about

the skills to maintain the quality inthe echo interpretation well, it's very important in a labto be first of all reproducible in the analysis to have the skills in performingstress test and the best should be to use exercise tests and this ispreferred also and mentioned in the recommendation but also you have to do withthe availability of the tests that are in your institutionand the skills that you have in your institution, so exercise imaging test areprobably the one to be preferred

but the probably most easy way to dois dobutamine stress echocardiography which isquite largely used in many institutionsbut, i think the take-home message for the wider community is there is a real problem with both sensitivityand specificity on what people were doing before with standard exercise treadmill testand ecg and thats not good enough in this day anage, 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 imagingtest i am saying with the original exercise ecg and we have to mention a specificpopulation who are women, that's a population thatdeserve specific attention because the presentation of the coronaryartery disease and the symptoms is sometimes difficult, and this is a population

in which the exercise testmay lead to wrong conclusions the same is true in older patients if i have to highlight what's the role of multimodalityimaging in the selection of patients who may berefer for tavi i would say that multimodality imagingplays a central role the first imaging technique to useis echocardiography because it will tell you wether thatpatient has severe aortic stenosis or not

and also if there are other factors thatmay influence your outcome like for example a poor ejection fraction or associated valvular diseaseand 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 ofmultimodality imaging has increased the number of patientswho are referred for that therapy but the results of the therapy themselves so, some messages about multimodality imagingand, what i take from this

is that we don't do all the investigationsin everyone we take a staged approach, geneviã¨ve 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 asort 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 selectionof the patient, a perfect selection of the way to do the procedure anda perfect selection to the identification of the good valveto be implanted so, it may help in improving the selection of thepatients the outcome of a procedure and in an organization, i think that's thefuture and that's the way to go to have integrated an imaging team

in order to select the optimal technique to answer the right questionsso, we've taken on board the need for the heart team and you'reemphasizing the imaging team we're not competing with each otherbut what is best for the patient and i would say that within the esc, we have taken this pointvery seriously by gathering together all the imaging specialities withinonly one association in order to help this dialogue to beperformed 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 thatangiography will have all the answers and actuallytavi is a perfect example where indeed it was not thecase and actually, if we see that now there issteadily improvement in the results imaging has a lot to do with that because the 2 most importantcomplications of tavi intervention, namely paravalvularaortic regurgitation and access side complication maybe reduced

if the patient is really screened wellwith multimodality imaging techniques and i would go further in saying thattoo 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 interventionnow the imaging guy

is part of the team in the cathlab, clearlyso, some clear messages now, barbara, as well as the guidelines they've been 2 large trials in diabetes presented at this congressand 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 affectmacrovascular complications in diabetes

but this is not happening, not only thatbut there is a suggestion that there is harm you are talking about the heart failure silviai'm talking about the heart failure signal in the saver-timi trialof saxagliptin so what should we do, frankwhat should we do about these big studies? well, in diabetes they are as barbara said, probably a little bitcarried away with all these numbers there were days where the diabetologist...we are talking about glucose

yes, they were talking too much aboutglucose probably and there were to happy when they couldlower their hba1c a bit then my endocrinologist back home,they were happy with that but whether that lowering ofglucose 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 presentedat esc showed well the endocrinologist would walkout of the room and say, great we lowered glucose andwe didn't do any harm

except in the heart failure,the cardiologist would say what's all this glucose lowering forif 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 ratherhave my glucose lowered and they weighed that more importantthan the heart failure i think we have to reshift that a bitbut microvascular complications are also important and they are glucose dependantbut they need to be shown for the new dpp4

that's true, but traditionally,we could say that the lowering glucose decreasesmicrovascular complications but the thing is, shall we say thenthat glucose is not a good biomarker for macrovascular, cardiovascularevents? well, it's ok but in diabetologyi think we have to tell them hypertension ace inhibitorsi don't think it's ok well, i think first comes that the best benefitcomes from a good ace inhibitor and a good statin, and the glucose...take one step back... we're asking whether glycatedhemoglobin

is a marker of macrovascularcomplications is is notsanjay, 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 realizedwith macrovascular disease in fact, i think we need to ease ofon the sweet spot and probably focus more on other risk factors for atherosclerosis

because in high-risk individuals,there is evidence that insulin, long-actinginsulin, have precipitated myocardial infarction and now the glitazones and the gliptinshave been associated with heart failure they seems actually to be a class effect ofglucose 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 gliptinsof the the trial presented

but i agree, hba1c isn't probably not a very good risk marker, that was outlined in theeditorial of the nejm as well and wearing your prevention hat, sanjay the diabetes patients, are we doingenough 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 tofocus more on the metabolic syndrome which we are not very good at doingin cardiology and i believe, my favorite

subject of course, is we need to push a little bit ofexercise 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 weekthat's all? yes, that's not a lotthey would reduce their risk factors their risk for cardiovascular diseasessignificantly not to mention all cause mortalityand 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 thelancet and more recent data based on 420,000 person-years,that have shown that for every met exercise you reduce your cardiovascularrisk by 13 % so, we've got a real challenge intranslating this out for the broader population because people are doing lessit's the best prescription that we can ever offer our patientsit's better than a statin than everything else, every device,every intervention, it's free

it doesn't involve a weighton 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 veryinteresting information coming from the murine models because it supports what was said before,when you have a murine model ofdiabetic cardiomyopathy once you have normalized the glucose

you still have myocardial functionabnormalities and on the other hand, when you havea murine model of exercise, even they aregetting older they improve their myocardial function with exercise so these micesare helpful yes, it's a positive message re-align is a phase 2 study in whichpatients with mechanical heart valves were randomly assigned to receiveeither dabigatran or warfarin we initially planned to have 400patients

to test this dosing regime, but in factthe study was stopped prematurely because of an excessof thrombotic events and bleeding complications they were clearly morethrombotic 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 amechanical valve and probably, if this hypothesis isalso correct you should also not prescribedthe oral anti xa

in patient with amechanical valve so, peter, dabigatran works inatrial fibrillation it's better than warfarin in thehigher dose in the atrial fibrillation studiesbut it doesn't work here, why? i think certainly by inhibiting thrombin you only do one step, so i thinkprobably 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 effector lack of effect with factor xa inhibitorso contact activation is really a an important issuethat 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 verydefensive when they say that we were misguided by thestudies in animals, but actually if you read the papers, the risk wasthere in animals

and also we should really start to doanimal studies in the same with the same rigorous methodsthat we use for human studies nowif we want to then translate these results into clinical investigationsi 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 fibrillationpopulation about 20 % have some extentof valvular disease and they're included in thosepopulations

so it is mechanical valvesthat are the exclusions we enrolled 740 patients with advanced heart failure and afterenrolment and implantation of a defibrillatoror a crt device patients were randomized toreceive standard care or home monitoring supportedtelemedical care after one year, telemonitoring demonstrated a significant impact on thepaci score primary endpoint with a significantly lower totalmortality rate

of 3 % versus 8.2 % in thecontrol group we can do something for heart failurepatients using this technology we simply have to do it right we need a high degree ofautomatisation home monitoring has it,we need short time lines and good flow ofinformation and we need a good chain ofinformation back to the patient,that something is changing we aimed to demonstrate that

crt is of benefit of patients withmechanical dyssynchrony and narrow qrs 809 patients with heart failurewho has qrs below 130 milliseconds and mechanical dyssynchronyassessed by echocardiography were included in echo-crt,icd were implanted to all and randomized to crt onor crt off the study was stopped prematurelyfor lack of efficacy and potential to harm with a higher totalmortality rate in the crt group

we found a surprising increase in all causemortality, p value of 0.02 we showed that there was an increase incardiovascular mortality actually driving all cause mortality what we could show and demonstratedtoday is that there is certainly not a benefit of crt in the narrow qrspatient, that the icd is the appropriate therapy for these patients again, very clear messagesso, frank, is the automatic telemonitoring ofpatients with heart failure the state of the art now well, not yet, we have to wait for thefinal paper

finally, some good news from thetelemonitoring front and finally some light at at the end of the tunnel what is making this different from thetrials that failed before? you know, there is an automatism with thishome monitoring device the patient does not really haveto do anything, so the compliance is 100 % it actually triggers an alarm buttonat those who look after the patient and then theytrigger 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, whattriggered the event, was it the afib, orwhatever it is, and what really they did, and what kind of interventiontook place which kind of help them reducing the eventsand that was quite remarkable no, it's not a state-of-the-art yetit's very interesting, very promising device, it looks spectacular but i think we have to wait for thefinal paper

to see that, but then we have 2negative studies, 1 positive but it's coming, they're gettingmore sophisticated, they are getting better so echo-crt, i think we need to take theecho off the title because that is a studythat 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 theresults show, for sure the other thing that is a little bitpuzzling is the mortality, you have an increase in mortality

and is not associated with an increasein hospitalization suggesting maybe arrhythmic death or other form of sudden deathin 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 timeago, many people told us that the vast majority of those witha 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 lastyears was in patients with narrow so there was a huge rational out thereand now we close the chapter it required definitive outcomeassessment and that's once again something silviasaid 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 adequatelypowered trial 115 centers worldwide,we closed the chapter and it hurts me because these patients

are many, these are the majorityof heart failure patients, we're running out of option they have a prognosis worse then cancerand 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 alsoin patients who have a clear-cut indication in the wide qrs, we learned onething from echo-crt on top of that as well ecg is back in the ring, the echois out, it's ecg that rules so, 130 milliseconds is the guide? well, 120 we know because it was very narrowin our trial, the main qrs was 105

with 120, it's dead below that,we know that above that, 120, we have still aia indication don't forget in care-hf,the mean qrs was around 150-160, there's a clearevidence but still there, we do not enough crt, we should do more there the biomarker in cardiology 8 study wasa process study, a prospective randomized study and we used the biomarkercopeptin in the bic-8 study, 902 patients

with suspected acute coronarysyndrome but initial negative troponin were randomized to either the experimental procedure withcopeptin measured on their initial blood sample orto the standard process we looked as major events as the primaryendpoint when we look at the primary endpoint,for maces at 30 day and we found that the mace wasvirtually 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 inthe copeptin arm were directly discharged from the ed versus 12 % in the standardgroup so peter, clear message?i think so, although again, a rather small trial, but finallyi think we really have a promising biomarker remember how many biomarkershave not made it to this stage,so i think it's promising andalso i think the linkage between the troponin

looking at myocardial necrosisand copeptin being linked to heart failure mechanismsis intriguing an early rule out, clearly important, a bigproportion of patients presenting and the current guidelines sayinghigh-sensitivity troponin 0 in 3 hours, now here's another playeri agree the genetic cardiomyopathies inparticular can be generated by a number ofdifferent genetic mutations,so one way to overcome this difficulty of developing thousand different drugs is the usethese class of molecules which are known

as chaperone this chaperone moleculewill basically mask the mutation, not correct genetically but mask it in terms of their functionalconsequences in this context, the melusin gene wasdelivered by adeno-associated virus vector tomice with genetic cardiomyopathy what we found, is that actually the mice, untreated mice, developpedas expected the cardiomyopathy but upon treatment with thismelusin gene

the mice are retaining their normalfunction for a very long time period an interesting take on cardiomyopathy,but gene therapy has had its up and down over the yearsand 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, mainlybecause the vector that were used were not appropriate,now with the advancement of new tissue specific vector, i think thatwe are seeing much

faster progresses, for example glybera isthe first therapy based on a adeno-associated virus that has come to the market for treatinglipoprotein lipase deficiency in the heart field, you knowwe have had already safety trial for heart failure patients withgene transfer so i think that, if you askspecifically the question now that we can do it where we want todo, it it's clear that in genetic diseases a niche of patients, veryselected

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 cardiomyopathyor in arrythmias as we have shown all approaches that can simplifytherapy, improve quality of life and survival in these individuals,so i would definitely think that is the first set of patients to testi think it's nice to see this progress terrific, now i'm gonna ask sanjayabout one of

the studies that hit the headlines inthe papers as well as the scientific press which is tour de france, and this is themortality figures in the tour de france and if you only read the headline, it saysthat if you are able to run, able to compete in the tour defrance, then you gonna live 7 years longer, now is this becauseyou've competed or is this because you are selected to bepeople 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 tourde france, the marathon and the iron man

that are very grueling and there is datathat athletes that finish these races around 50 % have high cardiactroponin levels and bnp levels and subsequent studies in the veteran athleteshave showed a high burden of atrial fibrillation and a threefold increasein myocardial fibrosis and therefore a possible surrogate thatsuch practice... so late fibrosis maybe one of the mechanismsthat drives the atrial fibrillation correct, so possibly a surrogate thatsuch practice may be safe would be to test longevityand that's exactly what the french group did and they demonstrateda 41 % reduction

in mortality compared with males in thegeneral 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 superiorto people who can't you are more likely to live a muchhealthier lifestyle and one thing that came out that trialwas a 72 % reduction from respiratory disease compared with the generalpopulation, suggesting that they were

much less likely to smoke very healthy cohort, so i think all we cansay is that if you are able to do the tour de france you are likely to live around7 years longer than the general ok, so, there's a take a message, now youknow 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 toyour cardiovascular system

as i mentioned earlier, there is datathat if you jog around 1 hour a week, or walk briskly at apace of 6.4 kms per hour you can reduce your cardiovascularrisk by 50 % so, that's pretty impressive! i want to come now to the take-homemessage from everyone and i want to start with yougenevieve, your take-home message for theaudience well, regarding the imaging technique,i think that you have to choose the best imaging techniqueaccording to the

clinical question which is raised,this is important and the other take-homemessage is using these new tools, fantastic toolsthat are available now do not prevent you forthinking 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 encourageall physicians listening to advocate exercise just as they do

abstinence from smoking for example and eating unhealthily, so i thinkexercise should be an important piece of advice thatshould be given to all patients that attend a physician frank? well, my take-home is that devices are veryinteresting and intriguing in cardiology but we learned from echo-crt and othertrials that even devices, as interesting as they look,they required definitive outcome assessments,we need the big trials

even in the device worldthat's true for renal denervation for mitral clip, for some crtindications and so forth let's push for thatpeter? you pass the ball right to me becausebig outcomes trial so i think that the take-home messagefor my part in acute cardiology acute cardiac care, would be to stoproutine use of thrombus aspiration in stemi patients, very simple, but veryimportant and also with great trial designsilvia? i would say that with all the trials that we haveseen, with positive, negative, contradictory

results as we have discussed the exercise of compiling guidelines isvery important, the esc is very active in these directions and i think that general cardiologistsshould really read carefully and critically the guidelines...and apply them and apply them of course, i think thatis important as well marco? i would say that thescandinavian colleague told us a new way of performing high-level clinical investigation, namelythis registry based

randomized clinical trials and of coursethis is something that should be expanded in the future but you will need such high leveland 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 therapeuticapproaches which of course will need to be tested but is nice tohave a completely different way

so, science and practice is not justfor the person at the bench it's actually for the clinicians and you know we've learned in thiscongress that definitive large trials have turned over what we thought was the evidence from smaller studiesand maybe that's one of the key take-home messagesi want to to close by thanking all of you, our volunteers forgiving up a lot of your valuable time in this process, i want to thank myco-chair, barbara for tremendous insights and all the workin doing this

for the entire team at the esc staff for the two sponsors, servier andastrazeneca for supporting the program and also aspecial thanks to the national societies who are usingthis 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 moreexciting congress next year, be thereyes, can't wait, see you in barcelona don't miss the esc congress 2014in barcelona

where everything comestogether