it's my pleasure uh this morning uh to welcome everybody to the annual uh Raiseback visiting professorship um and I just want to make a shout out to the Raisebacks um James and Sher Raybeck uh provided the the division with a large grant uh that we use both for education and also uh CG grants to our fellows and our junior faculty members and um Jamie died about three years ago but Sher continues to be uh very generous to the university as a whole and they they continue to fund both uh chairs and also grants um in multiple divisions and departments so um it's really my pleasure this morning to welcome Lyn Lynn Stevenson um as our raiseback visiting professor and we spent yesterday with her um she met a lot of the fellows and a lot of the faculty which was which was terrific thank you um many of you know Lynn um Lynn uh went to Princeton uh she graduated summi in biochemistry and then she went to Stanford medical school and then did her internship at Stanford and then her residency at UCLA in her cardiology uh fellowship at UCLA and um with that history of underachievement Lynn has continued to um make major contributions in the area of heart failure um Lynn was at UCLA where she uh led their heart failure uh efforts and then she went to the Brigham where she again led their heart failure efforts and now she's at Vanderbilt as director of cardiammyopathy um Lyn has been involved with really every major clinical trial heart failure that I can remember i mean she's really been at the forefront of figuring out how to take care of our patients with heart failure and as I told the fellows yesterday I think of all the people who I know at heart failure Lynn has really changed my approach to heart failure or my understanding of the pathophysiology and how to approach heart failure and I think that's true for a lot of us um in heart failure she's made major contributions we all know about warm and wet and cold and wet and actually that was Lynn's incredibly insightful way of assessing heart failure and we all use it every day in our clinical practice um this morning I just want to introduce her and we're thrilled that she's here and she's going to talk about guidelines in heart thank you good morning well it's such a pleasure to be here i've really really enjoyed my trip and very much appreciate James Resnik for helping us to get together here um it's really been a wonderful visit and I look forward to talking um to you um not advancing thank you um uh so I do want to say um I have no financial relationships at all and it will be pretty clear that I'm relatively unsympathetic to a fair number of the our industrial um partners um I've been in the guidelines uh committee for over 20 years and so I've seen a lot of versions and one of the things you realize is that there's rarely consensus among the committee so every time you see something it in fact um is the result of a lot of u collegial uh but sometimes relatively serious discussions so what we're going to talk about um reading between the heart failure guidelines we'll talk about heart failure staging it matter is what we call it uh the pillars of heart failure um how we apply guidelines to people in the hospital moving beyond GDMT give you a little bit of preview of um a new definition of stage C2D we'll talk about uh transitions and heart failure mid-range ejection fraction which um frankly I'm um not happy with that terminology talk a little about heart failure with preserved DF um let me just emphasize um I'm going to focus much more on heart failure with reduced than preserved ejection fraction um and devices are for another day although um there are many interesting things going on with the devices so it matters what you call it because that's how you decide how you're going to treat it um let me uh review um the staging of heart failure where we are currently um basically if um we start with stage B those are people who already have structural or um bio uh biochemical abnormalities u but don't yet have any symptoms and have not had symptoms stage C is symptomatic heart failure um but it becoming a little bit more granular where we have heart failure with improved ejection fraction we have persistent heart failure and then I'll talk a little about stage C2D uh which is sort of beyond the usual stage C and of course stage D is um a lot of what you see here in the an amazing transplant program that you have here you're very familiar with that um so it matters what causes it heart fear is a syndrome not the disease um that's one of the things I'm most known for in the selection committee meeting to say "Yeah I understand he's really sick but what's the disease?" Um and the recommendation is for patients presenting with heart failure the specific cause should be explored using additional laboratory testing and for appropriate management uh the 2022 guidance is the first time that genetic testing is mentioned in the guidelines back in 2013 there was a recommendation that you take a good family history um uh that certainly continues in the 2022 guidelines but now it's the first time as a 2A in select patients with non-eskeemic cardiopathy referral for genetic counseling and testing is reasonable and just want to emphasize however that absence of a family history does not mean that you don't have a genetic uh disease and similarly you may have a strong family history and yet we may not be able to find the gene the so-called gene elusive cardiopathy um I'm not going to talk about devices except for one thing which I think it's important to realize um which is that we have actually the least restrictive indication for primary prevention ICD in the 2022 guidelines which is that in patients with genetic arrhythmagogenic cardiamopathy with high risk features with an EF of less than 45 implantation of ICD is reasonable to decrease sudden death and I would point out it doesn't say you have to know what the gene is so if you have a someone with a very strong family history you can get them in under this indication um and as a preview I think we'll be moving to a time when an EF of less than 35 is neither necessary uh nor sufficient indication for a primary prevention ICD so let's move on to the pillars the three traditional pillars of medical therapy for heartbeat reduced ejection fraction through 2013 the ASOR ARBs beta blockers and mineral corticoid antagonists these have been incredibly effective people talk about them as sort of the old pillars but really this is the group of medications that really changed heart failure um marked decrease in sudden death even before ICDS we saw many people living for a long time despite low ejection fraction so this is a very powerful trio of therapies and this just uh reminds us of this this is a Danish nationwide study uh where they looked um at all the people in their country um and they looked at people who um had been hospitalized with heart failure a new diagnosis uh who were under 70 years and did not have any major comorbidity um and then they looked at those who were on ACE inhibitors and beta blockers by four months and then looked at what happened to them quite remarkable five-year mortality was only 14% in this group and of the survivors 78% had neither a hospitalization nor an increase in their diuretics during the five years and so this is just ACE inhibitors it's amazingly powerful therapies so we can't forget that when we look at the newer ones so cubital valartin is not just a new improved ARB it inhibits neproly which degrades many peptides um everybody thinks about the natriotic peptides as being uh the major effect of uh nephilyin in fact it turns out that&p is uh far more dominant than bnp we just don't measure it because it's so such a short halflife interesting um question as well is how important bradaine will be um because neprolyin breaks down bradkaine which has been implicated in some of the benefits of ACE inhibitors uh one of the things we find is that patients often feel remarkably better even if they weren't very bad before uh it turns out that neproly also breaks down endorphins and eneilins um and at least in animal models this may be important although it doesn't seem to be that important at least um when it's been assay in humans i just remind you it is combined with thalartin um combined with thalartin because neprolyin breaks down angotensin so if you don't inhibit the angotensin um receptor then you'll actually end up with an increase in angotensin which is obviously not what we want so paradigm heart failure um very well-known trial because it really changed the paradigm let me just review briefly how this trial was done because it's rather unusual um in order to get into the trial at all um you had to tolerate um an equivalent of a analopril or leinipril or R before you even got in the trial then you had to tolerate 10 milligrams twice a day of analopril then you had to tolerate 200 milligrams B of cubital valartin to get into the trial so we are selecting patients who can tolerate a robust dose to even get into the trial then once they got and this is a pretty healthy 70% class one um I think it was probably about half of the patients had never been hospitalized but this is a very healthy population and in that population um on top of everything else that they were on there was a significant benefit um in all the components of the endpoints um however um let me remind you that all these other trials that have gone on we ended up with a pretty low mortality group even before they got into the trial what this shows is the annualized mortality taken from the data in a lot of trials extrapolated back to get to one year and at the far end is the paradigm trial and you can see that the mortality is less than 10% and with Intresto it's a little more or less than 10% but we're not looking at a group of patients who are necessarily headed for early death so when we look at this picture up on the top um this was the original advertisement uh that was on TV for Entresto and it was quite frightening if any of you saw it this man's reading his book and the water's coming up and the dogs looking with terror at this man um it was actually taken off because um we all complained this is way too scary um when you look at this mortality down there so then they move to the next one um which is the guy that put the both the man and the uh dog in a boat um and then the last one which is really the most mild is that you know if you want to go out you know and have a nice date with your spouse um on the riverside that um and Tresto will help you do that more um so this is when I talk about reading between the guidelines it's very interesting to look at in 2017 which is after it was released um basically this was the guideline it was a level one um with very good data and it was basically included with ACE ARBs uh AR all included together um and said that the clinical strategy of renotensin system inhibition with any of these um basically is recommended to reduce morbidity mortality now here's the 2022 guideline it's a little different the top says in the patients with heft and class 2 to three symptoms use of AR is recommended so now it's just saying class two to three so what happened between 2017 and 2022 well one of the things if you go back and look at this trial despite having to tolerate these incredibly large doses of the renal antagotensin system antagonist um they went back and looked and uh pretty high incidence of hypotension even if you tolerated all that and this um is a study looking at it in relation to the B to the uh systolic blood pressure at the time of uh randomization and if your blood pressure um was I'm sorry 110 or less you had a quarter chance of having a hypotensive episode so in fact a little bit of concern about people's whose who whose blood pressure isn't that robust um and so what was happening is that um it was being recommended for everybody in the hospital out of the hospital uh and the life trial was done uh this is the only um skew valent trial that is not industry sponsored this NHLBI sponsored trial um with the HeartFhere Network to specifically look at people at the far end of the spectrum to try to define the boundaries here and so they took patients um who had been on GDMT and had one of multiple risk factors including recent heart failure hospitalization low peak V2 there was a um and in the hospital now there was a runin with secubital valartin and 17% dropped out the runin which is with the lowest dose an additional 17% were randomized also had hypo hypotension um compared to 12% with valartin and here's the result if you look at the incidence of CV death or heart failure hospitalization cubitrol valartin is not winning it's not anywhere close to winning no matter how long the trial had gone on um and the trial results were released during the finalization of the 2022 guidelines which is why class 4 was taken out of the recommendation for secure patrol valartin Uh so if we look at the complete wording basically um now it has class two to three for Arie but for ACE and ARB two to four remains in there and here's the summary figure uh list the Arie first for class two and three but ACE and ARB for class 4 because some patients are like the trial they're lifelike so now we're moving to four pillars i I was and is it four pillars because it's three pills um so it's a little confusing exactly how many pillars we have but let's move on to the next pillar uh now which is the SGL2 inhibitors uh their main obvious effect say increased glucose excretion in the urine which is why they were originally used for diabetes they have multiple other effects um this is just a combination of things um there's less uptitration of diuretics shown on the left in people on SGLT2 inhibitors um if you look at epigofloin uh there's data showing that it decreases uh the pulmonary artery pressure over a month this was from uh data with the implantable hemodynamic monitor um and if you look at clinical outcomes with kidney disease too this is something that we think probably affects the longerterm benefit of these agents because kidney function of course is one of the things uh that leads to worsening of heart failure outcomes specifically helpful just for people with kidney disease even without heart failure so how do we compare these two well John McMurray actually was involved in both trials and he calls it trying to um decide between your children um the if you look overall at the hazard ratios they're very similar uh for CV death and heart hospitalization 08 for paradigm 75 for the dapagloin but notice again the populations are very different so for paradigm you had to have robust blood pressure and tolerate that big runin there's no run-in period needed for SGLT2 antagonists you had to have a blood pressure over 95 um basically there are more people in um we've tested it in more people with more advanced heart failure so in fact it's pretty easy to start and most patients tolerate it um but um if you look at the hazard ratios um they look pretty similar now hazard ratios are relative but patients are absolute so how many patients do you need to treat to prevent an event um sorry just remind you here that um if we look um so this basically is a level one prevent looking at the number needed to treat now um for both of them to to to decrease one event of either death or heartfair hospitalization uh if we look at cubital valartin you have to treat 21 patients for 27 months to decrease one event so when a patient is not able to tolerate it I try to convince them in fact um that they're not dooming themselves to death without ceub and it's really important that we keep this in perspective and for CV death and heartfair hospitalization it's very similar for dapagloin uh for all cause death it's a higher number needed to treat and that's higher with dapagloin so now we have our four pillars so just to review these pillars the classic ones have been highly effective and tresto has further improved outcomes in class 2 threet inhibitors are recommended for a broad range of patients class one to four uh patients with diabetes with or without heart failure patients with or without kidney disease and as we'll talk about later it's across all EF let me just tell you I'm not saying the SGLT1 or two inhibitor because we do have sodoglyphloin which inhibits both one and two which has also been demonstrated but it is not life or death with these new ones i really want to get that across the number needed to treat it is is greater than 20 20 patients to prevent a heart fear event and 35 to 50 to prevent a death well where are diuretics in these guidelines we use a lot of those these four pillows in fact are going to just float away if we don't try to do something about congestion in people who have congestion we look back at 2013 um it's kind of um startling the only recommendations for diuretics were to improve symptoms and um it said there's no evidence for any other benefit it was often said diuretics treats diuretics treat symptoms but there's no basis of evidence that they include out improve outcomes and then observational studies show the use of diuretics and heart fear is associated with worse outcomes and higher doses are associated with the worst outcome well of course this is the problem of confounding by indication because the need for the therapy is what indicates the worst disease not the therapy you also have to be aware by the way of um the converse and observational studies confounding by contra indications the apparent benefit of taking a therapy uh basically um or higher doses of the therapy may also reflect that you've just selected a patient who can tolerate it not that the therapy is uh as good as you would think okay so here's um this is just shows you in this little diagram from 2013 that um it said that for um uh basically for um stage C class 1 to four first you do the ACE and ARBs and a beta blocker and if there's volume overload then you add a diuretic well this isn't the way we do it at all now one of the things and this is a concept um in terms of particularly for fellows who hopefully are watching us on Zoom um there's an inverse relationship between the weight of the impact of your therapy and how much evidence we can get from a randomized control trials uh and the um British Medical Journal had a classic on about parachutes we've got no data on parachutes that's because the impact is so great who's going to test that and I would say then somebody who's really short of breath who's going to test whether Lasix works or not who's and what patient wants the placebo so if we look at chloraladone for hypertension we've got hundreds and hundreds and hundreds of thousands of patients in those trials because they feel fine when they start it whether they take it or not um but we don't have much perfosomide to prevent and relieve congestion because it's a little closer to the to the parachute in terms of how important it is immediately so just bear in mind just because we don't have a trial doesn't mean that it's not very impactful and um in the pioneer study which looked at cubitual valart versus nalopril at discharge um despite you know this new therapy etc over 50% of patients needed a 50% increase in outpatient diuretic dose um within four to eight weeks so we really do need diuretics in many of these patients and here's some late breaking news in fact this won't really surprise any of you um but an observational trial of um about 8,000 patients in the optimized registry they took people who were admitted with heart failure without diuretics and then they looked to see who went home on diuretics um but the stunning thing was they were able to identify 2,000 of those patients who in fact went home without diuretics that to me was the startling part and a real surprise to you in fact they did worse and that even um doesn't account for the fact that most of them got started on diuretics soon after they went home so um this although it doesn't surprise anyone was considered to be really nice uh level B evidence so with this um we can now say that they do improve uh morbidity um and now for 2022 they're in there not only to um relieve congestion improve symptoms but to prevent worsening heart failure and it's now also um in the algorithm there um I'm just disappointed that the algorithm is actually done in gray like that so you can hardly read the thing that says address congestion but it does have that before you move on to the other therapies so we made some progress for diuretics so getting to dry before discharge uh now if we look at it says for patients requiring diuretic treatment during hospitalization the discharge regimen should include a plan for adjustment of diuretics but here's this small thing is it um the committee would not let us say should include diuretics because so we said well lots of people may turn out not to need them but it was okay to include a plan for diuretics so these subtleties in the guidelines often um hide a lot of discussion so just to review and we talked about this in a smaller meeting yesterday um we now are allowed to say that our major goal in someone hospital is to relieve congestion and then once that's well on target we move into optimization of guideline directed medical therapy so if we look at the guidelines um it says that basically titration of guideline directed medication um should be uh started and escalated as soon as possible and for um patients in hospital shown in the bottom GDMT should be initiated during hospitalization after clinical stability is achieved and it's hard to argue about that however it does come out to look at these two different strategies um one you can just start everything all at once or you can hit your target and sort of wait till you've um made some progress before you add everything together so SGLT inhibitors have actually specifically been tried in hospitalized patients um and um if we look at sodicloin for instance death and heart failure events um were decreased when you started it uh if we look at um the impulse trial dictate trial and I didn't update this but the dictate trial uh that Dr linenfeld lead um with embigphosin basically um sorry dapagloin um showed that you had an increased um amount of diaresis so now in the current pathway this is not the guidelines this is the ACC pathway for patients hospitalized SGLT inhibitors are now fine at any time during hospitalization uh MAS can also often be started if the potassium and renal function allow there's a little more likelihood of decreasing the blood pressure for a couple for um two to three millimeters uh with MAS but it's pretty reasonable to start them as long as renal function's okay um Larry Allen came up with a really nice concept of spending function which comes from investment framework uh for when you um have to decide what you're going to spend something on in the hospital the main spending functions are blood pressure um renal function and cost so just trying to keep those in mind and one of the things in the um revised version that just came out of the ACC pathway is think about how your patient came in when you try to decide what you're going to do with the neurohal antagonists in the hospital and this is roughly proportional uh to the um patients uh in the major trials in terms of the patients with a new heart failure diagnosis they're already going to be in the SGLT2 inhibitor now you need to personalize your initiation of the pillars of GDMT paying attention to the blood pressure and kidney function etc but most people in the hospital are in this middle circle they have chronic heart failure on partial GDMT and you need to decide the degree to which you can uptitrate doses or fill in the the gaps there but because of the life trial we now recognize that there is a group with chronic plas heart failure despite attempted GDM in which caution is required um to um initiate or uptitrate the renotensin um inhibitors or beta blockers and in those patients we may may need to re-evaluate it may be someone who should be considered uh for transplant or VAD you need to think about what's the long-term trajectory for those um so when we look at it we really need to individualize care this is one of my favorite slides it's the winner of the not my job award when we're thinking about painting lines um and the same thing with guidelines uh just following the guidelines is no excuse for doing something that's not the right thing for the patient so just to summarize the u pillars of medical therapy know the classic ones are very powerful army and SGLT2 inhibitors um but the benefit of new therapies can be overstated from looking at the relative ratios of benefit once congestion has occurred the diuretics are foundational to keep the pillars from flooding and patients who have been hospitalized require special consideration um so now I want to um give you a a very short preview um of what has now been called stage C2D heart failure c2 being sort of the um sicker end of stage C moving towards stage D uh so basically it falls into this gap between C2 and D what we call sort of the C2D and um to a great extent they are beyond GDMT um in terms of um deriving further benefit from that so this is a growing uh population estimated 250 to 300,000 patients in this group with ambulatory advanced heart failure uh one of the interesting subgroups is the palative inotropes about four to six thousand patients per year we know nothing about those patients um and yet there as many patients going for that as are going for transplant um and Shannon Dunlay has done a wonderful job of putting together a lot of this schema we don't know much about what to do with these patients if you look back at all our major trials of the heartbeat medications if you look at the dark bar those are the patients uh who have class four uh the not quite so dark is class three so we really have very little information about what to do in that C2D group so when did the pillars no longer support advancing heart failure something that we need to be looking into well deoxin I was talking with this with Dr fishbine is better than we recommended i if you go back and look at this you're going to be stunned if you compare it to things we currently look at so top left that is the benefit for death or heart failure hospitalization across the whole dig trial you look at this now and that's a blockbuster drug um all cause death was completely even death from heart failure um is less and this is the whole population if you look now at the class three and there very few class four in this uh it's an astonishing um impact as you look up here and if you look at the um EF less than 25 you see the same thing so there is clear benefit of dejoxin in this group of patients so we may want to think about it in the stage 2D it was just snubbed in the guidelines frankly I think to put it down at a 2B um is is really rather rude for what's a very powerful even if quite old drug um and then it of course gets a recommendation also um um for atrial fibrillation um not going to go into it it's not approved yet omacamp um is the measin activator uh and if you look at um the subgroup from that trial uh who had severe heart failure class 34 hospitalizations in six months this is the classic C2D patient and there's a remarkable benefit shown there and I'm happy that they have resurrected uh this drug and putting it back into trial so just to recognize this population and it's a call to action um who are these patients exactly well some of some of them could be the people who like went in the life trial patients who are rehospized with heart failure despite adherence and GDMT patients in whom you're diminishing your GDMT while you increase their diuretics and certainly Dr levy's Seattle heart failure score would be a very nice way I think to begin um classifying some of the patients uh in this C2D population so let me move on now um to transitions and the dreaded heart failure mid-range ejection fraction so um basically before we get there let me just have um a moment to tell you about heart fear improved ejection fraction which is a major component of the mid-range ejection fraction um this is not a country it's not a diagnosis it's a crossing in most cases first you exclude um some obvious things amaloidosis valve disease other restrictive disease people who have just had one MI um the patients remaining are mostly heart failure with reduced ejection fraction in transit up or some are heading down to a lower EF um this um for those of you who are old enough to know this is from um the movie Casablanca and Rick is examining the letters of transit to get people out of Casablanca in fact there's a lot of transit from this mid-range ejection fraction uh several studies show that um over the next two years that 45% increase 22% decrease and about 33% stay in the mid-range um so note that a lot of these people actually have the improved DF um this was first reported by Lynn Panuse um at at the bighgam um and basically it was called recovered at that time wrong term wrong term um so didn't um didn't name it very well but it's in fact a third of our clinics and we had no idea we were actually doing a study to compare hep and he reffinus came and said what am I going to do with all these people in the middle and it was stunning and then um basically I think uh uh it does matter what you call it um and I think that um the group from Baser which is a multic-enter group looking at this really helped us a lot because they pointed out uh that if you look at the patients who have um the so-called recovered EF which is down here in the green line it's still not normal because over the next eight years there was about a 20% chance uh of having an outcome and also that their biomarkers remain abnormal in many of them so here's a really complicated slide i don't want you to look at it in detail i just want you to realize it's really complicated this is the mid-range ejection fraction between 40 and 50 and it's full of all sorts of stuff most of them are the improved EF as I on the top start low and go high realize these people don't go to heft pep sometimes people think that you move back and forth between hep those i don't think so as I'll discuss I feel pretty strongly we shouldn't think about that as a continuum of one disease bunch of other kinds of diseases sarcoid myarditis toxins postmi can go in and out through the mid-range and then there's a group of restrictive who basically sit often in this range amaloid radiation adribramyc um very different diseases and hep is rarely um a specific cause of those some people with restrictive disease will prevent uh present with hep um hypertrophic cardiopathy can sometimes um so-called burnout and go to a mid-range we think rather than using burnout um we're now trying to change the terminology to um HCM with a reduced ejection fraction so well here's the recommendations for heartf mid-range ejection fraction um you're going to treat it just like he ref with the diuretics HL2 inhibitors and ACE arsen um but you're just going to give them a lower level of evidence i think this is really dangerous to think about this as one group of patients with one set of diseases um for instance if you have heart fear with improved EF yep we're supposed to continue it if EF is falling from normal it's probably reasonable to start it but what about aortic stenosis or mital stenosis well that's not very good therapy for them restrictive diseases beta blockers and renotensives and antagonist are often not tolerated amalidosis is dangerous if you use them so it's really important to treat the disease not treat the fact that they happen to have an EF between 40 and 50 now we're going to move on to hep which I'm not going to talk about very much um but I do want um to try to connect some of these things first of all it is defined by congestion okay that's the definition evidence of spontaneous provocable increased LV filling pressures or nitritic peptides that would reflect them so they share congestion and the cardioal interaction that's all the same um but is the therapy the same uh will neuro hormonal pillars actually keep hep out of the water there's much less activation and I don't have time to show you the data for that of uh those neuro hormones in hep so when it has been suggested as it has been um um from a significant group of people that back back that that heart failure is just one disease with EF moving across i think this is patently wrong it's going to mislead us we're calling it the wrong thing and we're not going to treat it right um because heartfelt with preserve injection is very different first of all beta blockers interesting study have been shown to increase hospitalizations and decrease exercise capacity so that doesn't seem to work very well we look at the pillars are actually reversed between hef and heft pep um in terms of everything is a 2B that is a level one um for heffre um cubital valartin um has not had benefit if your EF is over 57 no benefit and interestingly it's more beneficial in women than in men but it's clearly not the same as it is for he refinocorticoid antagonist still a much larger impact on he ref as shown here on the left for two hef trials on the right per heft pepf with spironolactone and most recently phenone looks exactly like spironolactone when you look at the impact on events um so although it's statistically significant it's clearly much less dramatic um than it is for he rev so people are asking if SGLT2 inhibitors after the data from deliver are now ready for level one um I think let's go back now and look at the issue of the number needed to treat This is now looking at the liver which is dapagloin in um heft pf versus he ref um if you look at the number needed to treat for instance um to prevent a death it's 111 so it's really not considered to have any impact um it's um 31 for death and hospitalization so clearly significantly less impact um than it is on the um he ref um let's talk a bit about obesity we're in a a red state in more than one more than one way if you look at obesity here compared to you have the enviable position of being a yellow state with a little less obesity um this is an study from ERIC looking at 10,000 patients and if you look in the pink bars he P he is marketkedly increased by obesity uh he ref only a little bit um as shown here in blue obesity is a major contributor to this disease and this is an old study um 30 years old very interesting though giving a saline load to people with obesity and no cardiovascular disease or diabetes and they can't get rid of it um they they they're unable to increase their trueic peptides um compared to normal people um and in fact that's probably a major component of hep this is GLP1 therapy um this is with semiglutide um a big winner at this point uh with semiglutide uh in patients with diabetes and patients without diabetes uh who have hep uh and so this is really an important thing now I think that uh perhaps will end up overshadowing the SGLT2 inhibitors um but here's an interesting thing um in a subset analysis looking at people who were on SGLT inhibitors showing that they basically did not show um the same benefit uh from adding semiglutides so we need a lot more information about how those two go together um this is I think a really interesting analysis um that was done showing the effective therapies for half ref from semiglutide SGLT2 inhibitors that basically they are very significantly affecting diuretic use and and the therapies that improve outcomes also decrease the need for diuretics which is not a surprise there's no um evidence of that uh for entrustto uh and some for spiron lactone here's the latest news that tzepide trial now adding uh the um gip peptide to the GLP-1 receptor antagonist um ef over 50 now so it's not quite normal it's not quite looking at the over 60 uh but you know clearly um an impressive endpoint um although pointing out that we have a pretty narrow scale in terms of the incidence of events um I'm sorry I didn't have time to make this more legible um I was just looking at this this morning and actually had not realized that there is this tiny signal although not statistically significant um for perhaps small increase in in in deaths um very small probably not significant but it's one of those things we need to watch uh as we get more trial data um there is a signal of possible harm for GLP-1 antagonists or agonists with heffref which comes from several different studies um looking at um uh both um eenotide and laglutide and semiglutide um that if we look at the patients who have he refilizations uh the falls on the wrong side um for each of the three of those suggesting that Um once again he ref and he PEF are not the same um so the next step I think it's hard to know um what's going to happen in terms of the guidelines next um so um as we move on just about done here I do want to go back to the fact that it matters what you call it now I want you to picture in your mind loosely picture failure if you had to give a photograph of failure what would it look like might look like this this is a failure of the bridge failure of the train certainly a failure of your vacation this is failure failure has very grim connotations asymptomatic heart failure what's that advanced heart failure like you you can fail then you're going to really fail um and then we have heart failure with normal F we all have these patients with heft pep well if my heart is a normal squeeze h how can I how can it be failing uh replacement is for hearts that are failing that's when you got used to using this basically if you have kidney failure go on dialysis if you have lung failure you know you're intubated but how can you have heart failure with no symptoms um John Cleland said it's time to take the failure out of heart failure totally by coincidence we both published in the same year on this um and who would be branded with failure first of all we have no celebrity champions for heart failure i mean we have it for erectile dysfunction for um Parkinson's disease we don't have it for heart failure so there's some reason that there's a stigma marches for failure we don't have that who wants to employ or insure a patient with failure and what do you do you ever talk to the taxi driver and he says so what meeting you going to part for your meeting goes oh the young people dream of going up into into failure we have a real problem and you have a real problem that we can't get people interested in this field do you suppose it's because they don't want to fail um maybe we should change the name and how do we recruit mid-level providers instead of waiting until they burn out from something else first I think we need to come up with a name and go out um into the country and recruit nurse practitioners because we need a lot more how about the patients are patients lining up to walk into these clinics how many of your patients say "I don't like that it says heart failure clinic on my appointment i don't have failure." Um interesting just in terms of history um so what is CHF used to be called congestive heart failure i mean that's that's what the CHF was for we tried to take the congestion out and then we just had to quietly change it to chronic heart failure so we have the same abbreviation um it's very hard to change this partly because of the pharmaceutical and device industries who all have their indications to give these therapies for heart failure so what could it stand now for if you didn't want to lose the initials well we think maybe challenged heart function might be something so that you can still keep your CHF name tag so this has been really a delightful visit and I'm so thankful uh to James Resnik and Sherry for sponsoring this so that we can get together um thank you for your attention that's such a wonderful talk i mean I feel like I've learned so much from you through the years i'm curious um there's so much data on guiding therapy um I know we touched just a little sequencing of medications and the reason why I asked that is there's so many therapies now the question is which one we start first i know there's some examples from viral perhaps we should start all medications at once to avoid treatment in but I think when patients are hypotensive side effects some you know kidney injury the question is which one would we start and my other question is when there's so many different therapies and the background therapy for each trial is a little bit different how do we know which one's better if or do we just put everything it's a great question it is the question um if you start them all at the same time I guess you don't have to think about it um maybe AI can take care of that for you um but you obviously have to make your decisions i think it's much easier in the outpatient clinic where somebody is stable they haven't had a recent exacerbation um and then you look at their blood pressure as you said you look at their renal function um you look at their kind of tolerability to get into this heavy medical world and decide at that point um certainly the easiest ones to start are SGLT inhibitors um the MRAs in somebody with normal renal function potassium pretty easy to start they don't usually cause problems um then after that I look at the heart rate and the blood pressure if the heart rate is high then I'm going to prefer a beta blocker and in general um I think most of us now would try to get people on a little bit of a beta blocker a little bit of andotensin and then work from there um they have to have a really robust blood pressure for me to go sort of um marching in with entrustto to start with um but if they have a nice blood pressure I I may do that but each one's individual and the problem is that most of the patients you see aren't like the patients in the trial patients in the trial a lot of them have never been hospitalized that that's not most of what we see in our clinic um so I don't think I have a good answer for you um that's what that's why we need people trained in this field and you wonder about them on an MRA or SGLT2 inhibitor and often you put them on it and then they have renal dysfunction hypotension orthostasis is and I'm always very reluctant especially adding the SGLT2 or the MRA if they are not congested and they are not on a loop diuretic if they're loop diuretic absolutely no issue but I wonder about the benefit when they have a normal BMP and they aren't on a loop yeah no I completely share your concern some of the data however comes from the fact that it's originally used in diabetes people who were not on diuretics and it did seem to decrease the first incidence of heart failure so if I think I can get away with it I would still like to do it but I worry much more uh I agree with you people not in a loop um I've had people I've had to take off of SGLT inhibitors because they keep getting hypoalmic so the neck veins are probably a good thing if you have someone who's got four or five which is of a lot of people i'm pretty nervous about starting SG u SGLT inhibitor um but um the U M I have not had trouble often with the MRAS for that i don't think that they cause that much diaresis but we clearly know I mean not not acutely it's sort of a slower slower progression um as we saw in hemodynamic monitoring like loop diuretics work very fast um but but the MRA work relatively slower but it's a really good question and people have to remember that oh we're really happy that you know it decrease your diuretic requirement but what if it's zero to start with um good point the second question related to that are people who are hypercalemic an MRA i have not been a huge advocate for potassium binders because of cost and other things and I'm just curious if you have an opinion on that i think we're both just too old um you know I don't like to give two drugs um but what's really interesting to me and the FDA in in some sort of unofficial settings has agreed I don't want to start a potassium binder to let me get an MRA until I have a placebo arm that's getting neither so somebody comes in with hypercalemia all the trials say if they've had hypercalemia they do better if you put them on a potassium binder well duh um that's that's sort of like most industry trials it's designed to win uh but my question is should I just stop the MRA and no one has answered that for me so I almost never use it um except in someone who has renal dysfunction that's bad enough that they have hyperinia anyway but I could be wrong but if someone needs to do the trial so I'm an electrophysiologist that's my disclosure uh you hinted at this I know i know um you hinted at this but what's the role of a primary prevention ICD in this population now that we're seeing a decrease in total mortality over time i'm surprised an EP guy would expect me to answer that in one sentence you still got a few minutes yeah no no it's um it's a really good point and in fact there was this um article I think it was Shen published it um in the New England Journal that said we don't need it anymore they have these lovely graphs that showed that sudden death has gone to almost zero but basically what they looked at was the same slide essentially that I showed you because mortality has gone down in the recent trials but those are in class two so um a lot of the assumptions that are in that article I think are not valid having said that it has clearly decreased and it decreased before ICDs it decreased with ACE inhibitors and beta blockers so it's definitely lower um um I think that basically we need to do more individualization of it i think um we need to be looking first of all once you take the people who have arithmogenic cardiammyopathy genes out of there and we look at the non-eskeemic I think we're going to find that we may not need to give it to all the others if they have no genetic disease no LG um and a negative culture I'm not sure we need to be doing it in in in very many of the non-eskeemics uh the MI group is quite different um and you know I think at this point if you look at even going way back to Scudf um the the eskeemics have more sudden death um so I think it's harder to say but for the non-eskeemics um I think we could start thinking a little more about it um but everyone's going to be very concerned about um legal implications so until there's a guideline that allows us to do this in Europe uh the indications for non-eskeemic have gone down to from one to 2A that's a still a pretty short answer to a complicated question hey Dr stevens thank you very much for the great talk um I was wondering with the with the results of the select trial and other similar trials on the cardiovascular outcomes of um GLP um drugs and GIP drugs and also with um ongoing discussions about potential expansion of those drugs for insurance coverage you know what do you think is the likelihood that in the future that uh GLP and GIP drugs would be drugs that are commonly prescribed by cardiologists especially given their impacts on heart failure and potentially for um for uh for cardiac uh arhythmias also um it's a really good question um how should we use it and you know I advocate having our primary care people um be you know take a little more care for heart failure so um I'm being kind of hypocritical when I say but I don't want to do anything with diabetes so I think we're all going to have to um increase our comfort zone a bit and we will end up prescribing some of them but you're right we really don't know what the impact is going to be across a broad group of people um it looks like in half refs so we're going to have to be pretty careful about that um there's some s some signal of increasing AIB um I think we have to be careful not to jump on that bandwagon too quickly but clearly it offers tremendous potential one of the things that I'm particularly excited about uh from a philosophical standpoint is that not noticing how much better people with hep get if you treat their obesity really I think turns things around to obesity is causing a lot of the hep i do want to have call out to Dr kurpatre in fact who's been uh inspirational in a lot of things he's done on our heart failure pathway in relation to how we should approach decision- making and um end of life discussions um and I'm hoping that you will get involved in the C2D um initiatives because there are a lot of issues there um about how we present things because unfortunately particularly at centers like yours and mine there's this feeling that when you have um C2D type heart failure you either need to go for transplant or VA or hospice and in fact this very large group of patients does not need to go to hospice yet we can help them to enjoy you know further meaningful life and I think we really need to work at that m middle ground and in fact I would say that a lot of your thinking on this issue of trying to change the paradigm of people who have endstage heart failure or cardiac disease in general who then get shunted off to hospice as the only option and rethinking our end of life therapies to allow lifep prolonging and decongestive therapies your your sort of advocacy for that I think has dramatically changed the way that we have begun to think about things from the ethics and the palative standpoint well and I think as I talk um about um what we call it matters we probably need to think about using this end of life phrase because it kind of presupposes the outcome and you know if I die two years from now am I at the end of my life now um and I think we need to realize that the remaining years are very very important to people there that was fabulous thank you so much i appreciate it putting ICDs in patients it seems like there is a misconception that patients have to I see like it gets lost i mean people just get a zero or two if you want