Heart Failure 2026 The Current State and Future Directions of Heart Failure Management

Indexed: 2026-05-18

[00:00:00]Good morning everyone. Thanks for being here this morning. Um have an exciting um grand rounds this morning and continued kind of in our our new theme this year of the updates in series. So I get to introduce Dr. Matthew Kaggleostro um who's here today to share um updates in heart failure with us. That being said, a little bit about Dr. Kagglestro.

[00:00:19]He completed his undergraduate studies at Duke University followed by completion of the dual degree MD MH program at the University of Miami Miller School of Medicine. He returned to New York thereafter completing internal medicine cardiology and advanced heart failure and transplant cardiology training here at Mount Si. He then stayed on at Mount Si with the advanced heart failure group. He has served as associate program director for the advanced heart failure transplant cardiology fellowship at Mountsai as well as an APD of the clinical track um Mount Sinai Elmherst cardiology training program. Please join me in welcoming him here today.

[00:00:56]>> Uh good morning everybody. Thank you for having me. Uh, you know, I was in your shoes not too long ago, so it's nice to be able to come up here and kind of talk to you all from this context. Um, updates and heart failure is a pretty massive topic. Um, we'll touch on some stuff less than maybe we ideally would, but with time we'll try to get through everything as we can. Um, and I'm just looking forward to to chatting with you all today. Um, I have no financial disclosures. So some objectives for today. Uh so we're initially going to just touch on some recent epidemiological developments in heart failure. Um then we're going to discuss the current heart failure classifications that we should be using when thinking about our patients in heart failure. We're going to elaborate on some of the basics of current medical therapy for both hef and heft. Um we're going to describe current and future directions of device therapy. probably something that you all see a little bit less in your clinical practice but I think one of the more exciting parts of our field in heart failure and then some future directions in medical therapy to keep an eye out for.

[00:02:03]So with that we'll jump right in. So starting with some epidemiology I think we all have a sense that heart failure is very prevalent. Um but just to put some numbers to it 6.7 million adults in the US um and one in 11 adults greater than the age of 65 have heart failure.

[00:02:20]Uh this actually came out recently in a in a Jack stats review which was a really nice summary of cardiovascular disease in the US. Um there is a differing geographic distribution. Um so you can see in New York we are uh for whatever it's worth in the deep deep red there uh with a very high prevalence per 100,000 persons of age adjusted heart failure. And heart failure in general is more common uh in the south and the east um likely due to various uh socioeconomic uh and comorbid disease uh characteristics that are different in these patient populations.

[00:02:57]As we might expect, heart failure gets worse with age and is more prevalent with age. So over one in 10 people in the US over the age of 80 have heart failure of some form. either half ref or he half heff. Um, and that is less common when you're younger but still notable particularly once you get to the 60 uh year old age category.

[00:03:23]How are we doing in heart failure? So, you can see that unfortunately these mortality uh uh lines imply that we're not doing the greatest job. Ever since 2011, there's been an uptick uh in mortality uh and a reversal of the gains that we made from 99 to 2011. You can see that across all age, sex, and race and ethnic groups that the mortality has been rising. Um, and one might want to think that that's mostly related to the co pandemic, but unfortunately it's more complex than that and is involved in uh increasing rates of chronic disease like hypertension, diabetes, uh an aging population in the US um and some gaps in care that continue despite our best efforts.

[00:04:11]So what are those gaps in care and what can we focus on? Uh this uh graphic was made in the context of 2023. So that's why there's not SGLT2 inhibitors because they had just kind of been on the market. But you can see with the green bars that the the green bars represent the patients that were missing. So GDMT, which we know is incredibly important and and effective in our heffref population is just being missed across the US. And as much as twothirds of patients are not on an MRA when they could be, 90% are not on an Arie when they could be and a third of patients are not on a beta blocker when they could be. So there's a lot of opportunity for us to talk in these forums and for us to improve access to care, not only from a provider perspective, but also from a greater systems perspective.

[00:05:00]Okay, now that we've talked about epidemiology, let's all get on the same page about some heart failure classifications.

[00:05:07]So what is heart failure? Uh so we often talk about diseases as entities defined by diagnostic studies. But what's really important about heart failure is it's considered a syndrome. So that means that not only do you need diagnostic studies that point you towards heart failure, you actually need the patient to feel that disease process. They need to have signs and symptoms of volume overload, lower extremity edema, shortness of breath as limited by their cardiovascular status. So it's that syndrome together that really defines heart failure.

[00:05:40]And so how do we take that syndrome and then classify it? So you'll hear us talk a lot in cardiology and heart failure about phenotyping the heart failure patient. Um which basically means understanding in a very heterogeneous population, what does that patient uh need and how do we take care of that patient best? And one of the ways that we can try to phenotype our patients is by classifying them. And in cardiology, we love acronyms and we love classification systems. So these are a few that I want you to kind of take away from this and think about when you see a patient with heart failure. So all comers we should classify by ACCHA, LV ejection fraction and NHA.

[00:06:19]If they have heart failure and they seem to be worsening, we should think about where they fit into the intermax classification. And then a kind of separate topic but worth just mentioning briefly is in the context of shock thinking about sky classifications. So we'll go through all of these now but before we do that we'll see if I'm reasonable at poll everywhere. Um so I'm going to put up a slide actually if you guys can try to join by poll everywhere here. There's a tiny little QR code in the top corner or you can just go to that website and then I'll flip back and show you the um the slides in a second.

[00:06:56]Okay. So, a 47year-old man with a history of non-obstructive coronary disease have f hypertension and a left bundle comes into clinic. He feels comfortable at rest but when he takes a shower and brushes his teeth he feels short of breath and he has no recent heart failure hospitalizations. He's on a decent regimen corvdolubsin spyro and empa and his blood pressure is 110 over 74. So how would you classify this patient? Um there's the link again if you need it and if we'll get a couple responses and then we'll go into this in more detail.

[00:07:38]And here is the question if you guys need that stem.

[00:07:50]Okay, see.

[00:07:53]Okay, getting a good mix.

[00:08:01]Okay, great. So, um it's actually seen.

[00:08:07]So this patient and we'll talk through why this is the case and this is why we why we do this talk is actually ACCHAC um classic heart failure stage that you see most frequently and he's NYHA class uh class three as well. Okay. So what are the stages and what are the classes?

[00:08:26]How can we um phenotype our patients better? So ACC AHA stages are a stage classification that's worth just understanding at its core. We use it in cardiology for any structural disease including heart failure but also valvular disease. So this paradigm applies broadly. Stage A is generally considered an at risk category. So these are patients that have not developed any signs or symptoms of heart failure. They have no structural changes of heart failure but they have risk factors.

[00:08:54]They're hypertensive. They're diabetic.

[00:08:56]They have a cancer that they received Adriomy for. they have family history or they have a genetic uh mutation without having developed any changes in their heart yet. These are the at risk patients. These are the patients that we don't see as often that you all see more frequently. Um and stage A can feel like a little bit what does that even mean?

[00:09:15]But it's just about understanding the risk factors that then will lead to heart failure that we want to try to modify early on in a patient's life.

[00:09:24]Stage B is preheart failure. So this is where the crux of that syndrome really comes in. So these patients may have a low EF. They may have left ventricular hypertrophy. They may have maybe some right ventricular dysfunction by echo, but they've never developed a syndrome of heart failure. They've never had volume overload. They've never been admitted to the hospital. They've never been short of breath because of their heart failure. Once they get to that category, they're consider considered stage C. This is the classic heart failure. This is the patient that you see all the time that you know has heart failure um and they have developed the syndrome. Once you go forward in these stages, you cannot go back. So once you've developed the syndrome, once you're stage C or worse and that's why we break down stage C into two different categories so that we can understand that population more. That population then gets break broken down into heart failure in remission. A term that's explicitly used in the guidelines because we know that cancer and heart failure mortality are very similar. So we're using kind of cancer terminology to make people understand how sick these patients are. And then also persistent heart failure, those patients that aren't doing better despite our best attempts, but are still fitting into this classic stage C group. And then the final stage, the stage that is my specialty is the advanced heart failure category. These are the patients that you all see on seven center that we bring in for these massive workups to figure out if they can be transplanted or receive durable elvad support or if we need to consider other options like hospice and paliotative care. And this is the end stages of heart failure.

[00:11:04]Okay. another classification, LVEF, probably the one that you're all most familiar with and is probably the easiest to wrap our heads around. Really just based off numbers. Um, a relatively incomplete classification system as we try to phenotype our patients, but nonetheless really important and kind of founds the underpinning of our therapies for these patients. Um, so 40% is the big cut off for reduced ejection fraction. 40 to 41 to 49 is this mildly reduced group that's very heterogeneous.

[00:11:33]And I'm not really covering so much in this talk for simplicity's purpose. He pf or a preserved ejection fraction EF of greater than or equal to 50%. A bit of a misnomer. Not a not a less sick population. Mortality is identical to the heffref group, but therapies are very different. And heart failure with an improved ejection fraction uh which is that patient that was halfreff and now has improved by at least 10% points in their EF and is above 40. One other just philosophical thing to bring from these guidelines. So that group used to be called heart failure with a recovered ejection fraction and you'll often see us write HFREC EF but it was reclassified as an improved EF category because uh our group our our field felt that recovered made people feel a little bit too good about these heart failure patients. Oh, maybe we can pull them off medical therapy because they're fully recovered. But the reality is that we know that once you've developed heart failure, that's now a chronic disease whether you've improved your EF or not.

[00:12:33]And so now it's been reclassified as an improved EF group.

[00:12:38]Okay. And then a couple more classifications. NHA, another one that you all will see a lot um from one to four, one being the uh the least sick and four being the most sick. So MHA1 while many of our patients are not going on the track and running the idea here is that they have basically normal activity and they can do it without feeling short of breath. NYHA2 I like to think of short of breath when you go outside of your house. So if you're doing ordinary activities in in short with uh NYHA2 class then you're getting short of breath. So going and walking to the grocery store, walking around the grocery store, um going on a walk in the park, that makes you feel short of breath. NYA3 I like to think of as short of breath in the home. So short of breath with normal daily activities. You get short of breath like our patient brushing your teeth or taking a shower and you feel limited in the house just with normal activities. And Nyha4 is our rest symptoms. These are the patients that basically can't do anything without feeling short of breath. As opposed to ACC AHA which you can't move back and you can't move backwards once you've move forwards. NHA the goal is to move you backwards. So our therapies are all designed at moving people from four to one and you can go back and forth. These are fluid classifications.

[00:13:59]Two more brief classifications just to understand are out there. So, Intermax, I talked about if a patient is worsening in their heart failure syndrome, try to think about how they fit into an Intermax classification. We realized as we looked at sick heart failure patients that NYHA did a really good job classifying ones, twos to threes, but when we were stuck in the 3, four for a while, it didn't do a good job phenotyping those patients. So, this is an attempt at breaking up na 3 and four into more narrow categories. And you can see seven is the least sick, one is the most sick, and one is is in cardiogenic shock. Um, understanding one other thing about this classification is that we tend to consider elvad and advanced therapies when we're getting into the one to four category, which is why it's boxed. Um, and so once you're developing those4 rest symptoms, if you're onotropes, if you're doing poorly on inotropes, or if you're in shock, that's when we're really thinking about advanced therapies. Um although a lot of our field is trying to study like where in intermax we should start we should be intervening and whether we should be inter intervening earlier than class 4 on intermax. Not something I expect you all to memorize but just look up intermax. If you have a patient that's admitted to the hospital or if you have a patient that's outpatient that's been admitted like four times in the past six months. Think about where they may fall on this classification.

[00:15:24]And while it's not really the scope of this talk, I think it would be a mistake of me to not mention the sky classification. You all will talk about this a lot in the CCU. Um, and this was a classification that was kind of built off of the ACCA in the context of shock and added this E category of extremis.

[00:15:42]So A is our at risk shock group. B are patients that have maybe some low blood pressure and high heart rate but are not hypo profusing. They haven't made a lactate yet. C is again our classic cardiogenic shock group. D is worsening despite what we're trying to do. And E are the patients that are really an extremist ECPR extremely sick. Um so when you have a patient in shock, cardiogenic shock, look at the sky classification, understand where they fall. Um patients can get can move between these categories. So we can make them better moving from D to C, for example. Um but this just helps us to phenotype and understand our heart failure patients so that we can better take care of them.

[00:16:24]Okay.

[00:16:25]Now on to the big topic of current medical therapy for heart failure of which I think a lot of you are familiar with but we'll just kind of lay the groundwork together uh to make sure we're all on the same page here. So another attempt at a question. Um, so let me have you log in for or it should be the same link, but just so you see this is where the question's going to going to go. And if anyone hasn't logged in, take a moment here.

[00:16:54]Okay, so here's the question. So 62-y old man with a history of coronary disease, heart failure who presents for follow-up. He's short of breath when walking outside. He can only walk a half a block. So probably NYHA3.

[00:17:08]Uh his home medications are a tennol, sucubenin, empa. Um and which of the following changes would be most consistent with an improvement in heffref GDMT? So would we change l uh cubatrolsartin to linipriil? Should we change a tennol to mtopriol suenate? A tenol to mtopriol tartrate. Should we add docysosin or add nephipene?

[00:17:38]minute here.

[00:17:48]Okay, let's see how we're doing.

[00:17:51]Wonderful. Okay, great. Um, okay, wonderful. So, you all got the right answer. So, the answer here is going to be to change a tennol to mtopol suxenate. and we'll go through why that would be the case and why the other answers are not the right answers. So this is actually from a relatively old guideline in today's world for years. Uh but it still forms the underpinning of what we're doing in heart failure in 2026. And you can see that um green is go. Uh it means that these are all class one indications, all the green boxes.

[00:18:25]And so really really high levels of evidence and high uh high community or uh uh general society recommendations here. So we're going to break this down a bit um and just kind of make sure that we're all on the same page with what we should be doing in heffre. So you can see that the guideline first off I just want to highlight is looking at stage C heart failure. That's that classic ACCA J heart failure group that we talked about on the slides a couple back and we're looking specifically at the heffref population for this uh phase. So RAS inhibition renin andotensin system blockade uh is kind of the underpinning of neurormonal antagonism that we like to do to calm down the natural human body's response to heart failure and these meds um form the underpinning of that. So they all fall into the same category. Subatrol balartin is uh likely the superior med in this group. Um, but you can consider using that versus an ARB versus an and an endotensin converting enzyme inhibitor. Um, and any of those groups of meds uh, work.

[00:19:34]There's not a class effect there.

[00:19:37]Beta blockers. So, this is the one that always trips everyone up. We only have three beta blockers that we can use in half. Carvadal, Mtopol, suxenate, and basoprolol.

[00:19:48]the mineralcocorticoid receptor antagonists get at the other part of the RAS cascade, the eldoststerone uh portion.

[00:19:56]Um and currently in guideline recommendation the only two that are recommended in hepheref are the steroidal MAS spyro and a plurinone although there are studies ongoing in the use of a non-steroidal MRA called finerone which has already been shown to be efficacious in hemf and hep now in the he um he ref population so reduced sgt2 inhibitors I feel like are one of the more exciting drugs that we talk about um and have been shown to be really effective across EF categories but definitely in low EFs um and we specifically have because of the trials EMPA and DAPA although it's not necessarily thought to be a class effect and then diuretics while they're not necessarily a GDMT that changes outcomes in heart failure they are relevant for symptoms and um you'll see here that we are predominantly using loop diuretics I put the ratio of ferosomide to bummetite to tosside and oral formulation there.

[00:21:00]Um and we're often then using thazides to augment diaresis. Um as well as considering uh carbonic anhydrates inhibitors uh to help decongest our patients.

[00:21:11]One important point that I mentioned kind of in passing is that the beta blocker group is not a class effect. And what does that mean? So that means that as we've studied these meds in every group except for uh the beta blocker group when they've been studied in heart failure with a reduced ejection fraction they've been shown to make an impact.

[00:21:29]However, there have been at least two trials in beta blockers that have not shown to have a positive effect on outcomes in heart failure patients. And these are the only three that have been shown to make a difference. So you cannot use a non uh GDMT beta blocker in heff and expect the same outcome. Uh and it's very important to know that beta blockers are not a class effect. You have to use one of these three.

[00:21:54]Okay.

[00:21:56]Once we've used the pillars of GDMT, how do we then uh take care of people if they're still not doing well? So persistent halfreft despite our best efforts. Um then we're thinking about adding other therapies. So the guideline uh had a class one recommendation for hydro nitrates. Um so I like to think about it in terms of if my patient is MHA 3 to four and still not doing well, they're hypertensive, they're on the max of what I can get them on from the four pillars, then I'm going to go to hydra nitrates as another option or another pillar. Uh in addition, you may consider evabine in the right population. um particularly in patients that have heart rates above 70 that are in sinus despite a max beta blocker and you may consider veraiguat although the data here is maybe not the strongest in a patient who's on as much GDMT as they can but are still doing worse um you may consider adding vericuat which is a soluble guano cycles stimulator okay um and then I think we all have this sense but if they keep with a low EF and they have a good survival and they and they have anything but really advanced NHA symptoms, they should be considered for a primary prevention ICD um uh to to improve long-term survival because of the risk of sudden cardiac death in those patients. And we'll talk a little bit later on when we get to the device section about the benefit of CRT in this population.

[00:23:26]Okay, couple quick tips before we move on to hep. I often get asked on seven center which GDMT should we start first and the answer is there's not really a right answer and we have to phenotype the patient but as a general rule if they're congested I like to think about RAS inhibition you want to reduce their afterload think about a vasoddilator if you don't have the kidney room um if you reduce their afterload you reduce their SVR then they're going to improve their forward flow and they're going to decongest more effectively if they're uic able to tolerate the negative inotrop effect of a beta blocker. So, you could think about a beta blocker in that patient.

[00:24:05]Reassess their ventricular function 3 to 6 months after target or maximally tolerated doses are achieved. Don't do it two weeks after you got them on the max dose of intresto. Give their heart time to to remodel. Uh but also don't wait two years because you really want to see how they're doing and whether you need to consider an ICD if their ejection fraction is not improving. For example, this sounds silly, but therapeutic inertia I always compare to when I was at IMA seeing a patient who was a poorly controlled diabetic and being like, oh, I don't know, do I go up on the insulin?

[00:24:35]What if they get hypoglycemic? So, there was a tendency to have therapeutic inertia in that group. And heart failure is the same. If we're always scared of what the GDMT is going to do and we never start anything, then it never gets started. And we know that these meds have a big survival um and outcome impact on these patients. So don't be scared. Start it. Reach out to us and we'll help. And then these uh meds were studied at particular doses. So don't don't aim above those doses. Aim for the targets. Um even if they seem like they're doing well, they're 120 over 80, they have NYHA1 symptoms, but their EF is still low, push the the GDMT to the target doses that were achieved in those trials. And then lastly, one of the biggest questions we get is, "My heart's better. can I come off these meds? And while we're still understanding how to phenotype this group of patients, the general recommendation is to stay on meds unless there's a side effect that we're trying to mitigate by taking people off.

[00:25:36]Okay, now we're going to move on to hep um this is going to this is a question.

[00:25:41]Um I'll activate it here. Um if anyone didn't log on yet, you can log on now.

[00:25:50]And actually the whole question's here on the slide so we can just stay on this slide.

[00:25:56]So which medication class used commonly in he ref GDMT is not generally recommended and in fact sometimes contraindicated in heft pep optimal medical therapy.

[00:26:09]Good. We're all unified on our responses here. Um and we're all correct. So beta blockers are not a foundational therapy and heft pepf and despite that patients are frequently put on it um without really thinking about it. Sometimes because of corobid cororbid disease and sometimes not but they actually can have a negative impact in heffref populations because of various things including chronotropic incompetence and should not be used routinely. So what should we be using? So hep is hard. Heepf is a very heterogeneous group and there are a lot of comorbid diseases that drive the syndrome of hepev. So the first part is be a good doctor and take care of the hep patient and we as cardiologists need to be good internists when we take care of these people and you all found the underpinning of what is a good heft pepf patient's medical therapy because if we don't treat their OSA their hypertension their diabetes we don't treat their hep so treat their coorbid disease control their blood pressure and address their metabolic syndrome when we thought about that then what do we think about specific cardiac meds that we can using FPF and you can see that as opposed to heffref there's a lot of orange and not a lot of green here. Um Dr. Halperin, one of my mentors, one of our I think all of our mentors uh summarized it well by saying a class one you should definitely do, a class 2 A you should probably do, a class 2B you maybe shouldn't do, and a class 3 you shouldn't do. So we have a lot of 2Bs here and I just want to go through some of the data with you all so you can understand why these are 2Bs so that we can understand the strength of our recommendations around this category.

[00:27:49]So why are SGLT2 inhibitors a 2A indication? So because of two main trials emperor preserved which looked at empaglyphilis versus placebo and had a really really nice p value for the primary outcome of cardiovascular death or heart failure hospitalizations. This was driven by heart failure hospitalizations but because of this trial um EMPA was approved as a class 2A indication in HEFA. The same thing happened with DAPA. The liver showed almost the same curve. It looks like they just had the same exact data. Um and uh again primary outcome being the composite of death and heart failure hospitalizations driven by heart failure hospitalizations was shown to be very very effective. um and as a result of 2A indication.

[00:28:38]So why as opposed to that are all of these other ones now 2Bs? So Arie uh was first studied in the Paramount Paramount AFHF trial that was a phase two and that showed that BNPs came down although only statistically significant at week 12 and lost statistical significance maybe because of loss of followup by week 36.

[00:29:04]Paragon HF um which was the first trial in HEFP comparing Arie versus Sartin um unfortunately did not meet stat statistical significance. Now you can see on these slides it makes it look like these lines diverge but the p value was not achieved. It was effective only in subgroup analyses looking at specifically a lower EF less than or equal to 57% and in and in um female populations.

[00:29:31]And lastly, Paraglide HF, which took the patient population and started in Tresto also in the inpatient setting um did show an improvement in BNPS um but not an improvement in mortality or heart failure hospitalizations except for in subgroup analyses. Again, looking at a lower EF category in this group, 40 to 60% uh younger patients less than 65 and those that identified as black or African-American from a racial category were all shown to be beneficial in subgroup analyses. So given relatively weak data compared to other medications, this got a 2B recommendation. Um, and I personally use ARES when I'm seeing a hypertensive and very congested patient that is doing poorly despite my attempts at optimizing other heft pep therapy.

[00:30:24]What about ARB trials? This is why ARBs were compared to Aries in the first uh case. So charm preserved was candin versus placebo. This actually did not reach statistical significance but was just there 051 for the primary outcome of cardiovascular death or heart failure admission. It did reduce heart failure admissions however um but then they restudied it with herbicartin and there was no difference across any outcome. So because of these somewhat mixed results this also got a tub recommendation.

[00:30:57]We're using it as an anti-hypertensive in the HEPF group because of some of this data, but not the strongest recommendation.

[00:31:04]And then the last 2B recommendation is the MRA group. Feel like this is like a seven center like pop quiz all the time.

[00:31:12]What's top cat and why is it an interesting trial? And it's because Spyro unfortunately was the product of probably some issues on trial design and and um trial in action. So it did reduce heart failure hospitalizations. This was an older trial but it did not show s statistically significant reduction in death, aborted cardiac death or heart failure hospitalizations.

[00:31:36]But it was weird, you know, it seemed like there were some signals for benefit and some signals for lack of benefit. So people did a deeper dive and tried to see why was this actually the case and what happened. And when they did a deeper dive looking at the two arms that were in this trial, there was one arm in Russia and Georgia, the country, and one arm in the Americas, we noted that outcomes were vastly different. Outcomes of of side effects, rates of hypercalemia, rates of AKI, and then just generally uh like event rates were very very different between these two trials. And you can see that the blue arms are just totally disperate to the red arms here. And you can see that the red arms do seem to show a benefit of spyro potentially. And so because of this subgroup analysis, it's a subgroup analysis, so it can't be more than a 2B recommendation. But we do do still feel that there's a possible benefit in symptomatic hep with a EF greater than 45% congestion and an okay renal function. And this was further proven to likely be the case um be with the fine arts trial which uh recently looked at finerone versus placebo and showed a reduction in heart failure hospitalizations and CB death which was driven by heart failure hospitalizations as a result of the initial top cat trial. It's still a 2B but it's one of those 2Bs that I think most heart failure providers really think of as a 2A and we use more readily than we would use other 2B recommendations.

[00:33:06]Okay. And lastly in this group the most exciting drug that we all seem to not stop talking about the GLP1 RAS. Um so this is specifically studied in heart failure in the context of a BMI above 30. And there are two drugs that we currently have approved. Semaglutide and tzepatide. Uh tzepide adds this uh gip pathway to the GLP1 pathway and both were studied with basically identical outcomes. So step hep was specifically the hep semoglutide study and summit was the tzepatide study. Both showing a reduction in the composite of CV death and heart failure hospitalizations driven by heart failure hospitalizations and semlutide and other studies was shown to improve quality of life in six minute walk. As a result of this, we have GLP-1 as a recommendation, not yet in the updated guidelines, but still a recommendation for HEF and obese patients to be on a GLP-1 for improvement in cardiovascular outcomes.

[00:34:08]Okay. All right. Let's take a breath.

[00:34:11]Heepf. This is HEF medical therapy. And we've gotten through the medical therapy portion of the talk and now we're going to do a little bit of device discussion just to kind of round out the next few minutes.

[00:34:23]So this is not really a a quiz that you get right or wrong, but just a way of assessing how familiar you are with these different therapies. So which of the following are you familiar with or have interacted with in clinical practice? And you should be able to select multiple when you pull up this slide. So, cardiac recynchronization therapy, pulmonary artery sensors, MVtier, TV or TTVR, sorry, not TTVt, uh, CCM and VAT often. For the sake of time, we'll keep going, but this breakdown is what what we would expect people being very familiar with CRT and PA sensors and maybe a little bit less with the rest.

[00:35:05]So we'll take the next few minutes to just go through what these are in broad terms so that you're familiar with the concepts.

[00:35:12]So one disclaimer here. So in some of what I'll talk about, you'll ask how did this get approved? It seems like it's way too early for these therapies to be out in uh standard use. And uh it's because of a breakthrough device program that exists in the US that expedites release of markets for devices targeting life-threatening or irreversibly debilitating conditions. So as an example, CCM and BAT are shown to be very effective in the initial trials, but the indications are a little bit narrowed and that's because they came quickly to market because of the fact that they were addressing a a patient population that was very very sick. And then a disclaimer is that we're still trying to figure out how to navigate this space. So um I may seem a little bit not fully committal to one or the other and that's because the device world of heart failure is very complex and having getting p patients through um that pathway into the right device can be a little bit complicated.

[00:36:15]Okay. So starting with one that we all I think were familiar with uh CRT. So what is CRT? CRT is a device that a pacemaker that um implants a lead into the right side and the left side of the heart to enable simultaneous BV pacing. This then enables electromechanical synchrony which improves cardiac output instead of one side beating against the other.

[00:36:39]Everything's beating together and the cardiac output goes up. This has been shown to reduce heart failure hospitalizations all cause mortality and improve quality of life.

[00:36:50]How do I want you all to think about when to use this? Obviously, you want to talk to your cardiologist, but if you see a patient with heart failure and they have a really wide QRS, then think about this. That wide QRS is a sign of potential dissynchrony that would benefit from recynchronization.

[00:37:08]So, all left bundles are either a 2A or a one indication and really wide non-left bundles are a two-way indication. And then patients that are requiring very frequent pacing should also be considered for CRT. And this is really become so much a part of what we do in heart failure that it's jokingly called the fifth pillar of GDMT. Um, and should really be considered in the right patient population and we should be looking at every EKG regardless. But when we're thinking about optimal therapy, looking at the EKG for your heart failure patient to make sure that there's is or is not an indication for this therapy.

[00:37:46]MV tier, Mitroclipip or Pascal are the two that you may see in the market. Um we talk a lot about and just to touch on briefly here when it would be indicated.

[00:37:56]So mitro regurgitation is often comorbid with heart failure and can be linked to poor outcomes. uh the difficulty can be teasing out whether the mital regurgitation is from just the heart being weak or cardiammyopathy or whether it's related to uh the valve itself and whether there can be things about the valve that can be fixed.

[00:38:18]>> So uh this is specifically looking at um moderate to severe secondary mitro regurgitation from the ventricle being bigger or dysfunctional. Um, and what we want to really hit at is that patient population that has what we call disproportionate mitro regurgitation.

[00:38:36]That's a complex term maybe that just basically means that the heart's not as weak as the MR is bad. So the heart is weak. 20 to 50% EF is the group that we're looking at with the MVtier population, but it's not a 10% EF that's massively dilated. um it's uh 30% EF that's not horribly dilated but the MR is really really bad and in those patients what we know is that if we then fix the MR hopefully they can get better in the long term. um a really complex idea, but just to know that in those patients with severe sec moderate to severe secondary MR that are still limited that we should be considering MVT in those patients and it's a perccutaneous procedure where we're crossing the interatrial septum and putting a little clip on the mitro valve um similar to what's called the alfier stitch in cardiothoracic surgery to then reduce the area of mitro regurgitation.

[00:39:34]Everyone was also pretty familiar with PA sensors. Just to speak a little bit to what these are. So these are devices which are implanted through catheterization procedures that are placed in the pulmonary artery and allow us to hemodynamically monitor uh waveforms of pulmonary pressures and titrate diaresis. Um these are remote monitoring systems that patients become a part of their body. They go home, they lay on what we call a pillow, which is a a bad term because it's very uncomfortable. Um uh and then that transmits to us here in the office and we can call them and say, "Oh, you have a little more fluid now. Why don't you go up on the diuretic?" The cardium is the only one that's in clinical practice right now, but the Cordella is being actively studied. Uh and we are implanting both of these devices here at Mount Si. The indication is that symptomatic nyha three or4 patient who has been hospitalized within the past 12 months. That's a pretty broad category.

[00:40:31]So we want to make sure we're accessing these patients and helping them at home, helping keep them out of the hospital.

[00:40:37]Um so think about this when you see a heart failure patient.

[00:40:42]Okay. And now we're going on to a couple categories which maybe are a little bit less fully understood uh but still part of our general recommendations for consideration. So tricuspid interventions similar to the mitral but now on the right side in patients with severe TR um that have had signs and symptoms are associated with that TR uh uh sites lower extremity edema heart failure right-sided heart failure hospitalizations despite optimal medical therapy we can think about tricuspid um edgetoedge repairs or also replacing the valve uh through the TTVR are the outcomes here have been positive but mostly been associated with quality of life improvements and reductions in TR volume. And so while we do want to call our structural colleagues and think about this in our patients with severe TR and symptoms um just know that this space is still being actively built out and understood in terms of what the right step is when.

[00:41:44]Okay. Okay. Now, two therapies that um that I think no one was familiar with and and I I wouldn't be in your shoes either. So, let's go through what these two therapies are before we wrap up. So, cardiac contractility modulation or CCM, the idea here is that weak hearts don't use calcium effectively. And so, is there a way that we can prime the mioardium to improve calcium use, which then we know improves contractility? And so this device what it does is it applies a signal during the refractory period to the RV septum and that in theory then primes the um myioardium to release more calcium and use more calcium more effectively uh and then to have better contractility. In the initial trials it did show an improved uh oxygen consumption which is a marker of cardoppulmonary fitness. It improved quality of life in NYJ class and it reduced heart failure hospitalizations.

[00:42:40]It is an implantable device um and uh it is implanted by our EP colleagues um and it is modified uh in the outpatient setting and clinic to try to optimize the signals. We should be considering this in NHA 3 to four symptoms with LBFS 25 to 45 with a narrow QRS. So they shouldn't have a CRT indication and they have to be in sinus rhythm.

[00:43:10]And then uh lastly of the six that I initially talked about barrel reflex activation therapy. We know that in heart failure sympathetic overdrive drives a lot of the negative outcomes.

[00:43:21]And so is there a way that we can try to simulate the parasympathetics and oppose some of that. And this kind of gets at that. Um this is showing a pathway through the corateed barrel receptors that activates the brain stem to then activate the vagus nerve and have that parasympathetic tone hopefully overcome sympathetic tone. And as a result of this idea um this device essentially is implanted by typically a vascular or cardiothoracic surgeon with a stimulator by the corateed barrel receptors that then gets titrated to effect and hopefully improves uh parasympathetic tone and reduces sympathetic tone. when it was studied uh it improved exercise capacity quality of life of N&T probnps and it should be considered an NHA 2 to3 EF less than or equal to 35% with no indication for CRT as well okay two more slides to wrap up just in future directions so future directions for devices I've already shown you a bunch of devices that are very exciting and stuff that we still are trying to learn more about and there are several devices that are still very much in the trial phase of understanding. Acusinch um uh is a trial that's looking at a perccutaneous um device that gets kind of sewn into the myioardium um through minimally invasive techniques and is I is intended to reduce the negative remodeling of the ventricle and to cause positive remodeling and to hopefully improve ejection fraction and cardiac function.

[00:44:56]There's also another mitro valve uh procedure which puts a little contour system through the coronary sinus to narrow the orifice of the mitro valve and reduce mitro regurgitation that's being actively studied. And then there's these four that you'll see summarized on this graphic here. Um so the vagus nerve stimulator is intended to again optimize parasympathetic output um through a stimulator that's implanted by the vagus nerve. Splanknic nerve modulation is a trial that was done here uh rebalance that looked at ablation of the splanknic nerve in heftp patients. Um that was done by our EP colleagues with with uh Dr. Mitter if anyone knew him. um diaphragmatic stimulators which modulate the amount of fluid that is uh brought into the intrathoracic space and then fire one which we're going to be starting soon is another um volume pressure um remote monitoring system that's implanted in the IVC. So a lot of really really exciting things that we're doing in this space and a lot to look out for in the device world of heart failure. And then I'll just wrap up with some therapeutics to consider that we'll think about as more data comes to fruition. So I said GLP1s are like the most exciting thing on the field it seems. And part of that is that there's just so much that we can target. I don't put this slide up to expect you to read any of it, but just to know that this was a recent paper out of or a brief paper out of JAMAMA that showed six additional pathways that are being studied in addition to semiglutide and tzepide. Uh some of which we're going to be doing here at Mount Sinai and trial formulation. Um, so just know that this path, this group of meds is going to just become more and more on the market and more and more relevant to our patients and something to keep an eye out for in terms of understanding what the differences will ultimately be.

[00:46:55]Macccarbal is a cardiac meosin activator that you may have seen come out in a trial a couple years back that's also being actively studied in the Heffre group. And then we're just trying to figure out with the last three meds that I'll put up there how to best act how to best target the eldoststerone pathway.

[00:47:11]We know that six 66% of patients are not on it when they should be on it. And part of that is that these meds have side effects. They cause hypercalemia.

[00:47:19]They cause AKI. So are there ways that we can mitigate that? Fenerinone I talked about is being studied in half ref. um balinone with dapagly is being studied across EFS and is uh supposed to be a more targeted um medication for that pathway which will reduce the risk of hypercalemia. And lastly, uh, Backstreat is an eldoststerone synthes inhibitor that similarly is intended to hopefully reduce some of the negative side effects of spyro and aparone and improve uh, adherence and placement on the pathway to complete that renin andotensin eldoststerone system blockade.

[00:47:58]Okay, so now rounding out just with some take-home points. So heart failure is super common. 6.7 million adults in the US with rising mortality and a lot to do to try to improve outcomes in these patients. When we're looking at our heart failure patients, we should aim to classify and phenotype them considering the use of EF, accropate intermax and sky.

[00:48:22]We should try to optimize all pillars.

[00:48:23]Think about EF. But regardless of EF, we know we have so many meds available. So look to optimize all pillars of their medical therapy and don't let therapeutic inertia get in the way.

[00:48:35]Think about device therapy. Think about it earlier. We should think about devices earlier than we are across our field as well. Um and think about current and investigational options. And then keep a lookout for exciting developments in the medical and device related therapies for patients with heart failure.

[00:48:53]Thank you everybody.

[00:49:12]Thank you everyone.

[00:49:18]>> Mhm.

[00:49:23]for the folks who aren't.

[00:49:34]>> Yeah, it's a good it's a good question.

[00:49:36]I don't actually know how this particular group defined that, but usually they're like doing a pretty this this stats was like aggregating a bunch of different resources and so they are usually doing a pretty deep dive to clarify if there were contraindications.

[00:49:51]Part of this is what bore out into like some of our discharge pathways for you all as you discharge our meds with heart failure to really like select why you don't have them on it because the therapeutic inertia around heart failure is so great. Um so I don't know the fine details of how they did it but uh they were pretty clear in what I was looking at around this that these patients truly didn't have a contraindication.

[00:50:20]Uh-huh.

[00:50:27]So, cardiac rehab and heart failure has been shown to be effective. Um, insurance often becomes the barrier to that, but in a heft ref population, it's usually approvable. Uh, we have a great cardiac rehab group here. So, you could consider referring there. If they have an ejection fraction of less than 35%, they do require they do some form of stress testing in our lab um called a cardopulmonary exercise test. You could think about that. And then we do know in general that activity is good, right? So the recommendations for activity don't drop off because of a patient having heart failure. And so it's really important to recommend that your patients stay active um because we know that cardopulmonary fitness is not just related to the heart, it's the whole body. And if they're uh they develop a general skeletal myopathy from heart failure. So to mitigate that staying active is important.

[00:51:27]>> Yeah. So it's so complex and I think this is a field that's exciting and that we're still learning so much about it.

[00:51:34]um the GLP-1 pathways, I mean, thinking about the amount of potential indications that are now coming out around it just show you how complex the pathways of understanding are. Um, and so with heart failure, there's this whole cardioabolic field that's now come out. SGLT2 inhibitors, GLPs, and then all the other pathways that are like GLPs that I showed you like like amret um amalin rather and other pathways along that those lines. We think that they have like a anti-inflammatory effect. They and they affect a lot more hormonal pathways and neuro like neuro gut and neuro heart pathways than we even really understand. So it's really really complex but what we do know is that it reduced outcomes that we didn't necessarily expect it to. Similar to SGLC2s which were studied really in diabetes but then we saw massive drops in mace. GLPs had a bigger impact than we thought they would even have purely from it's not just weight loss, it's cardioabolic.

[00:52:36]Awesome. Thanks everybody.