Chapters Transcript Video Heart Failure with Preserved Ejection Fraction Back to Symposium All right, yeah, so I just joined a little bit less than a year ago, and we're gonna try to get through this tour de force of, uh, heart failure with preserved ejection fraction, or as we all know it, halfpef. So stick with me through the end of the day here. I don't have any relevant disclosures. So for today, we're gonna define HPE. We're gonna talk about the diagnosis, the management, and some other special entities that we'll see in the HPEf realm, things like amyloid and hypertrophic cardiomyopathy or HCM. Start off with a case. So we got a 71-year-old female. She's got a history of diabetes, Afib, hypertension, obesity. For the past 6 months, she's had dyspnea on exertion that's been worsening really the past 2 weeks. Now she's having 2 to 3 pillow orthopnea and 2 weeks of lower extremity swelling. On exam, her BMI is 34, her heart rate's 70, her blood pressure is a little bit high at 141/87. Her JVP is elevated up to 10 centimeters of water. Her lungs are clear. Her heart is regular. She has 2+ edema bilaterally to the shins. Her echo shows a little bit of increased wall thickness with her septum 1.3 centimeters. Her ejection fraction is 57%. Her right ventricular systolic pressure is 43, and she has some mild aortic stenosis. This is, I'm sure somebody that all of you guys have seen in clinic at some point in time. So what exactly is half path or heart failure with preserved ejection fraction? Uh, so to diagnose this, we really have to have the clinical syndrome of heart failure. And what is that? Well, those are the signs and symptoms that we're probably all well aware of uh paroxysmal nocturn nocturnal dyspnea, orthopnea, dyspnea on exertion, fatigue, decreased exercise tolerance, leg edema, elevated JVP with positive, uh, hepatojugular reflex, cardiomegaly, pulmonary edema, all these are signs and symptoms of heart failure. They have to have a normal EF or at least uh greater than or equal to 50%. Then they have to have some objective evidence of either resting or provocable elevated left ventricular filling pressures, things like an elevated B-type natriuretic peptide or BNP or non-invasive and invasive hemodynamic measurements. So if we think about our patient that we just brought up, she had orthopnea, she had dys on exertion, she had leg edema, she had decreased exercise tolerance, and she had non-invasive markers of elevated filling pressures with an elevated right ventricular systolic pressure. So when we talk about the prevalence and mortality of HefPf just in terms of thinking about heart failure in today's world, the most recent statistics would show us that about 6.7 million Americans are living with heart failure per person lifetime incidence of about a quarter. So that's quite a large proportion of patients in our population that have heart failure. And nowadays, actually greater than 50% of that is HPE, so it is on the rise. Why is that? Well, we're seeing more of an older population as people are living longer. They're living with more comorbidities, things like diabetes, hypertension, obesity, and this interplay of the cardiovascular kidney metabolic syndrome, or CKM. The one year mortality of patients with Heppe is quite high, 20 to 29%, with frequent hospitalizations. This is a large burden on the healthcare system as well as, uh, on the morbidity of our patients themselves. It's highly prevalent, but I know a lot of us feel like, well, it's hard to sort of slap that diagnosis on. Even myself, I saw someone in the clinic and she's like, Well, what do I have? I was like, Well, you probably have half pf, but we sort of have to get into the nitty gritty sometimes, and it'd be hard because, um, well, it's a diagnosis of exclusion, so you have to rule out other things that have specific physiology and treatment. If you look at the last, uh, the cardiac causes, things like hypertensive heart disease. Valvular heart disease, constrictive pericarditis, restrictive cardiomyopathies, HCM, amyloid, sarcoid, there can be other non-cardiac mimickers, things like liver failure, renal failure, obesity that just have edema, anemia, pulmonary disease, um, just chronic venous insufficiency, and a lot of these patients have the gambit of comorbidities that we see in our patients and mentioned in the patient earlier. Uh, when we look at the heart failure guidelines, this is sort of, uh, you know, hard to follow on the screen, but it's essentially what we've been doing so far is that when you're thinking about diagnosing it, you need to get into the history, you examine them, you get an ECG, you get some labs like BNP, you get an echo. An echo would rule out just about, uh, a lot of the things on the left side or at least point you in the right direction on all of those cardiac etiologies. So you start there and then you stratify it by the ejection fraction. And you get a little bit further into the weeds past that if you think you're dealing with something in in specific, and we'll get a little bit more of that later. When you talk about a BNP, that's an NTR BNP that's greater than 125 or a BNP that's greater than 35. However, A normal BNP does not exclude HPE, and an elevated BNP does not confirm HFPE. I'm sure, I'm sure you've seen that, you know, we get this console all the time. Hey, their BNP is up. It's like, yeah, but they're on dialysis, you know, who cares about the heart, um, so, you know, it's very much neither one way or the other, but it's a helpful tool that we use to sort of follow and understand where our patients might be clinically, and it certainly has prognostic, uh, ramifications that we all, uh, know and, and certainly follow. When we talk about the echo findings, I'm not sure how much in the weeds we've gotten into echo so far today, but this is, you know, one of the crux of heart failure and diastology. Um, diastolic dysfunction is not hefpef. I think, you know, we've called it diastolic heart failure for a long time, like we all to try to just get rid of that term because when we talk about diastolic dysfunction, that can be people who have a low ejection fraction that have a normal ejection fraction. It can be people who don't even have the clinical syndrome of heart failure but have diastolic dysfunction. So diastolic dysfunction is really an abnormality in relaxation and filling separate from the EF or symptoms, um. And the echo findings alone cannot make or exclude the diagnosis of heart failure as, or HPE as we recall, they have to have all the things that we mentioned earlier, which is really the clinical syndrome of heart failure. Some of the things we see on echocardiography would be increased LV wall thickness, increased left atrial volume index at least greater than 34, uh, and then some Doppler tissue imaging. And what does this mean? Well, if, if I had to take 2 seconds to try to describe diastology, I think the pump squeeze is easier for us all to sort of visualize. The pump has to squeeze well, and when the pump. isn't squeezing well, that makes sense. But what actually happens in diastology or the filling of the left ventricle is that the annulus is pulling down and pulling blood out of the atrium into the ventricle. It's a lot less that the atrium itself is actually squeezing and a lot more that that annulus is moving down. So if we look at our people who have terrible diastolic. Function, there's really not much pull and you look at a young individual has a heart that's cranking away, that thing's moving a lot to suck volume and blood into the left ventricle. So if we stick a little Doppler signal over the mitral and lateral annulus and we watch it move up and down, the more movement is going to be consistent with more normal diastolic dysfunction and decreased movement is going to be considered less, uh, or, you know, abnormal diastolic function. And that's really the core for where we start with our diastology grading. Then we look to see, are they having evidence of elevated filling pressures. So that big E there on the screen is gonna be what happens when the mitral valve opens. When the mitral valve opens, the atrium has not contracted yet, but there's that pull down, and there's gonna be a rush of blood that goes into the left ventricle. And when you have really high filling pressures, you know, because it's not pulling down sufficiently, then those elevated filling pressures in the left atrium have to sort of force everything forward. And that's what's happening in chronic heart failure. You have a long buildup of elevated left atrial filling pressures. The inside that mitral valve opens, you get a rush of blood in, you get a really big E wave, and those are evidence of elevated filling pressures. There's other things that we look at in comparison to that initial opening in blood flow versus the actual squeeze of the atrium themselves. And then I mentioned elevated pulmonary pressures as evidenced, uh, by increased tricuspid regurgitation velocities. And so this is the 2025 diastrology guidelines that just came out. Um, there's a lot to unpack here if you just look at the first three top things, it's basically what I was just trying to describe is that movement of the annulus or the E velocity has to be somewhat reduced, and then you have to have evidence of elevated filling pressures. That's that big E over the E and then increased pulmonary pressures or TR velocity. Beyond that, we get in a little bit of the nitty gritty in terms of how we grade it, but that's sort of the basis in terms of thinking about, well. Well, is this heart, are the mechanics not working appropriately, even though the pump function is normal? And that's a lot of what guides us to say that this clinical syndrome of heart failure that's happening might be somewhat, at least in part due to the heart. You know, people can have this diastolic dysfunction, have terrible kidney disease, and their heart failure could still be related to their kidney disease. So it doesn't make or break the diagnosis of HefPf, but it's certainly the crux of what we do and what we understand as relationships to the heart. Um, there's other scoring systems that can help us diagnose, and these are easy to do, easy to look up. The H2FPF score, you guys might have heard before, but if patients have an ejection fracture and it's greater than 40%, you can add up some of these markers to understand if people have, uh, may, may have HPE or not. These are people with an elevated BMI. They have, uh, more than 2 antihypertensives. They have atrial fibrillation to some degree. They have pulmonary hypertension. Uh, maybe they're older than 60 and they have elevated filling pressures, kind of what I was describing before. If we think about our patient from earlier, they had a BMI of 34. They weren't antihypertensives, at least in my STEM. Uh, they have A fib, which is a big point. Um, they have pulmonary hypertension. They were over 60, and I didn't mention anything about their filling pressures, but let's just say that they did not have elevated filling pressures. That person's score is 70, which gives them a greater than 90% likelihood of having HPath. So you can feel pretty confident in saying, yeah, I think that what's going on in this individual is probably H path, and we need to treat it as such. And the other sort of parameters where maybe you're not as sure it's a little bit lower on the scoring system, we have to do something else. And a lot of times, in fact, 1/3 of patients with HPE have normal filling pressures at rest. You see them, they're saying, I'm old, I'm short of breath when I try to move around. You examine their their them their JVP is normal. They have no lower extremity swelling. You even are maybe fancy enough to do, look at their IVC on ultrasound, you see that it's not, uh, plump and it's not, you know, uh, full of fluid. Well, these individuals, you have to stress them to some degree to understand if they have provocable elevated filling pressures. Uh, so you can do this with either invasive or non-invasive measures. You can take them to the exercise lab and either do things like a cardiopulmonary exercise test, a CPET, or you can do exercise echocardiography, or you can take them to the lab and do exercise right heart catheterization. Someone might have a normal wedge pressure or less than 15 at rest when you do their right heart cath, and then you lift their legs up. If with leg raises alone, their wedge goes up higher than 20, that might be consistent with heft Pf. Or if you exercise them, which most of the time in a lot of labs, it's a little bit easier to have a stationary bike, you stick them on the bike with increasing resistance and their wedge goes higher than 25, well, then that might be HPfs as well. So you really have to perturb the system to understand if they have HPf or not. I mentioned a lot of other things that can get in the way of understanding or at least, you know, be other things that we have to tease out because HPf in of itself is a diagnosis of of exclusion. So sometimes we have to do other things like cardiac MRI, genetic testing, PYP scans if we think that it is amyloid, and we'll talk a little bit more about that in detail. So, OK, let's move on to management, which finally we have something exciting to talk about because for the last, I don't know how many decades there has not been much other than manage the blood pressure, manage the volume, but there's a lot more that's come out and I'll show you that even the last guidelines in 2022 are now really getting out of date. But historically speaking, it was more in line with this, which is that you would manage their blood pressure. Uh, there was already data by these guidelines to talk about SGLT2 inhibitors, and we'll get into that, but certainly managing their comorbidities, especially atrial fibrillation. Thinking about maybe mineral mineral chloroide receptor antagonists like spironolactone, uh, ARBs and Arnies or Entresto might help sort of decrease hospitalizations. That's why the latter three there get a 2B recommendation, the earlier two get a 2A, and managing their blood pressure is at least a 1A. So the 2022 guidelines said, sure, you know, give them diuretics, keep them uvolemic, definitely SGLT2 inhibitors are a good idea, and then maybe some of these other agents, but as I mentioned, this is already out of date, and we'll talk about the nowadays HPE pillars and hopefully have some new updates in the next, uh, couple of years to actually make this sort of go out in the guidelines. But certainly SGLT2 inhibitors at the top of that list, uh, MRAs, both steroidal and non-steroidal or phenerinone, and we'll talk a little bit about that. Um, there's indications for patients to be on GLPs, uh, and then ARB and RE in certain situations. So when it comes to SGLT-2 inhibitors, I think we all know a lot about these by now, but there's two main trials, one of which came out before the most recent guidelines, the Emperor Preserved, which looked at impogliflocsin or Jardiance, and then the more recent, uh, Dapogliflocsin, which was in 2022, just after the guidelines came out. But both of these were randomized controlled trials, so a drug versus placebo. They both got 10 mg of either Farxiga or Jardiance. They were NYHA class 2 to 4. They had an EF that was at least greater than 40%, and they had some marker of congestion, which was an elevated BNP. It's about 6000 patients in both studies, so a pretty good size study, and the endpoints was a combination of cardiovascular death or heart failure hospitalizations. Uh, deliver included, uh, urgent care visits. Um, both drugs were associated with a 20 to 21% reduction in this combined endpoint. There's a benefit across the spectrum of ejection fraction. Now I'll say that hospitalization was really the primary driver if you look at this data, but there are some meta-analysis usually in both studies that show that there is an individual benefit to cardiovascular death in of itself. But this came out, and I think this has led to all of us to say that yes, this is, uh, this is gonna be a class one recommendation for SGLT-2 inhibitors in patients with HFPF. Uh, as you can see, the ESC or European Society of Cardiology guidelines have already come out, um, a couple of years ago now and have put this up at a class one right next to diuretics and treatment for underlying etiologies. Why do these drugs work? Well, if you think about the problems in HPf, they have oxidative stress, they have inflammation, they have fibrosis, they're volume overloaded, they have cardiac remodeling, hypertrophy, etc. Um, SGLT2 inhibitors will decrease your nitric or improve the nitric oxide pathway. They improve metabolism, energetics, and they have natuuresis to help decrease the diuretics or make them, uh, diurese more and keep them out of the hospital. What about mineral MRAs or, uh, spironolactone? So we've had a data that's been around for some time. The TopCT trial, which was a negative trial from a few years back now, is about 3500 patients. It did not meet the combined endpoint of cardiovascular death and heart failure hospitalizations. Heart failure hospitalization is about 12% versus 14%. Um, we looked to make sure that patients had an appropriate rise in creatinine and potassium to say that they're taking the drug. However, there was some certainly funny business in this. About half of the study was from, uh, the Americas, and the other half was from, uh, Russia and the Republic state of Georgia. And if you look at the rate of heart failure hospitalizations, uh, in comparison of the two different, uh, regions, you'll see that the Americas had a lot more heart for hospitalizations, which you would certainly expect in this population of patients. They're ended up in the hospital all the time versus Russia and Georgia did not have as much, so there's a question as to. The degree of heart failure in that other patient population and then if you're not included here but if you look at a graph of the rise of potassium and creatinine in these patients in the Americas it certainly went up and then in the state of Georgia and Russia it didn't change significantly so it was a question of whether or not um they were actually getting this drug so I think suffice to say we've all been using these drugs in HP for a long time and it's, you know, something that we would recommend across the board. However, because of this negative trial, it only got a 2B recommendation in the last set of guidelines to decrease heart failure hospitalizations. Fast forward to the fine arts trial that has come out in just the past couple of years now which had about 6000 patients greater than equal to ejection fraction of 40%. This was a phase 3 randomized placebo controlled trial of Fenarinone which is a non-steroidal, uh, MRI. Uh, with patients with again he ref or half PE, and it was a combination of cardiovascular death and heart failure hospitalizations, and we saw a significant result in this trial. So we finally had a positive trial for MRAs, um, a 16% risk reduction in primary endpoint with an 18% reduction in heart failure hospitalizations. So there's definitely a benefit, uh, to these drugs in HPE, and we were wondering, well, by now a lot of these patients were on SGLTN-2 inhibitors. Was this just driven by that? And the study actually showed that it was independent of their use of SGLT-2 inhibitors. So certainly a drug that we all think is fair to use, um, you know, whether or not to reach for spironolactone orpharinone, I think, you know, there's some differences in how we think about that. I think both would be reasonable for a large portion of our population, especially if you have a hard time getting some of these other drugs. But there's, uh, other trials that have come out, the Figaro DKD and Fidelio DKD that looked at benefits of phenarinone and CKD in diabetes to reduce hospitalizations, and certainly those are all positive. So again, the ESC has already given this a Class 1A recommendation as a second pillar of HFPf to use phenarinone in patients with HPE, especially those with type 2 diabetes and CKD. So the GLPs, there's been a couple of studies that I'll talk about. The first study was the STEP Hef-PEF trial, which looked at simmaglatide. This is a randomized controlled trial in patients with HefPf with or without diabetes. It was about 600 patients. They got simmaglatide versus placebo. It was a 52 week trial, and they looked at their, uh, KCCQ or Kansas City Cardiomyopathy Questionnaire scoring, which is basically, uh, quality of life, weight change, 6 minute walk distance, and CRP or inflammation. There was a significant difference in terms of their KCCQ score, about 7.3 points. We look at some of the other trials that have looked at GDMT and HAFRA, the, uh, largest, you know, think about, uh, Entresto, SGLT2 inhibitors. Those had KCCQ scores of around up to 2.5. So this is significantly different, uh, in terms of how much better these patients are feeling, and they all lost weight. Um, they had better 6 minute walk distance and their markers of inflammation went down. Well, this sort of makes sense. You put them on a drug that helps them to lose weight, they lose weight and they feel better. What we wanted to know is, does this help relieve with heart failure? Uh, well, certainly losing weight can help symptoms. We know that lower weight reduces plasma volume, uh, and there's other inflammatory pathways that improve when we decrease weight. So the next trial that came out in 2024 was a summit trial looking at terzepetide, the combined GIP and GLP-1. It was about 731 patients, a randomized controlled trial, uh, patients with HPE and a BMI greater than 30, and they got increasing doses of terzepetide as would be appropriate. Uh, it was a composite of adjudicated death from cardiovascular causes or worsening heart failure events, and this was a positive trial, so. And they had a 38% risk reduction in time to first occurrence of heart failure outcomes. Their KCCQ scores all improved drastically. They had a drastic improvement of body weight. Um, so we're all sort of happy and expecting this to some degree. However, I will say in a group of 700 patients, the amount of heart failure events were relatively low. There's only 29 heart failure events in the, uh, um, in the group getting the terzepetide and only 52 in the other group. So as of. Right now, this is undergoing FDA approval to see if this will be approved for HFPA. More to come on this. I think we're all hoping that this certainly will be helpful and needless to say, when you're thinking about HFPE, managing the comorbidities is something that we should do, so it is certainly helpful to some degree. I'll just briefly go over Arnie's and ARB's, uh, but there's been two sort of trials looking at this in the Hef Pf population. Paradigm was the Hef ref trial for Entresto oracubitril valsartan, and Paragon HF was the trial for, um, uh, Entresto in patients with preserved ejection fraction with an EF at least greater than 45%. It's a pretty large trial, 4800 patients, give or take. Entresto versus valsartan. It looked at the composite of cardiovascular death and heart failure hospitalization. This did not meet statistical significance. However, it was only about 6 events away in the valsartan group from meeting statistical significance. And when you look at the subgroup of patients who were on the lower spectrum of ejection fraction and were women, they seemed to derive greater benefit. It's a similar sort of result in the CHARM trial, which is a little bit older trial looking at candesartan, but same sort of deal. So that's why in the current guidelines and moving forward, you know, this would probably maybe stick a 2B, maybe a 2A for certain patient populations to say that this can help decrease their heart failure hospitalization. Certainly if you have someone that's sort of borderline ejection fraction, maybe a little bit lower, they have hypertension, these would be good drugs to reach to as a first option. Just like to drive home the importance of the multidisciplinary care that's important in these pathways. It's in these patients. It's good that we're all being like this today because, you know, we can't just do it in cardiology or heart failure. This comes to more than you guys than us. It goes to the nephrologist, to the endocrinologist, to everyone all above when we're managing the multiple comorbidities that drive hef pf. So there have been multiple articles that have sort of talked about the importance of all of us talking together, um, but just to talk about a couple, a couple of things when your spidey senses need to come out, patients that are a little bit younger than 60, maybe they don't have all those comorbidities that we mentioned, they have some progressive symptoms, they have, uh, thick walls but low QRS voltage on their EKG, and they have some family history that's pretty significant for heart failure. Well, this would make you think about other etiologies, things such as amyloidosis. So patients who have had biceps, tendon rupture, who've had bilateral carpal tunnel, who've had things like trigger fingers, spinal canal stenosis, multiple, um, hip or knee replacements, who have heart failure, a fib. Maybe they have some GI symptoms that aren't really well explained like nausea, vomiting, diarrhea, constipation, or they have some degree of autonomic dysfunction and certainly peripheral neuropathy. These are all signs and symptoms that can happen in patients with amyloidosis, and a lot of these predate having heart failure. So, you know, carpal tunnel is something that can come 10 years. In fact, we're already working with our, um, carpal tunnel surgeons to sort of, you know, when they're doing bilateral to actually take snippets and send it off for Congo red staining, and I've certainly had a few patients come through my clinic because they found a positive Congo red staining or evidence of amyloid on those, uh, carpal tunnel surgeries. But there's two main types of amyloid that affect the heart. There's a million types of amyloid that affect different organ systems, but two that we care about when it comes to the heart, and that's AL or light chain amyloidosis and ATTR or transthyretin amyloidosis. So looking at the left side of the screen, AL is really, um, an oncologic emergency. It's a plasma cell dysrasia, so a little bit more rare, but as you see later in the diagnostic algorithm, we're checking light chains, um. And markers of elevated M proteins on all these people to see if they have some evidence of a plasma cell dysgrasia because we always need to rule that out as a cause, but some plasma cells going crazy, making a bunch of these fibrils, those are forming and then going into different tissues and depositing, uh, causing multiple issues in the heart later on. And then transthyretin amyloid, the way that that works, we have these, um, tetrameres that come from the liver. It's basically pre-albumin is the, is the type of protein that we're looking at. As we get older, especially, these can start to break up. Those individual monomers form fibrils. Those fibrils go and form into different structures and cause problems. So there's a, there's been a lot of data in this in the past few years now and certainly as we've come to uh have more treatments for this uh disease, uh, as I mentioned, you might get some clues from the history you're gonna go through your diagnostic algorithm which is to send monoclonal proteins, so kappa lambda light chains, uh, and then SPEP with immunofixation and UPEP with immunofixation and there's actually, um. There's an order set for this. If you just type amyloid, if you're suspicious, it'll come up with these type of orders as well as sort of the next step, if, you know, if you've ruled out if all the light chains look good, so you're not dealing with AL, fantastic, and you're still worried about amyloid, then you can go down the route of transthyretin amyloid and get a PYP scan, which can be diagnosed diagnostic in of itself without having to do invasive measures in diagnosing transthyretin cardiac amyloid. There's been a few different therapies that have come out, and I'll try to zip through this because I'm probably running low on time, but you probably know about Tefamiitus or Vindamax that's been around since the Atra trial in 2018. Uh, that was our first sort of therapy that's come around. It's a stabilizer, so if you sort of think back to this slide with that tetramere in the top right, um, as opposed to letting it break up into all those monomers and then causing problems, it stabilizes and keep it, keeps it in that tetramere shape. So that's how stabilizers work. None of that doesn't necessarily reverse the process that's there, but it can sort of stop it in its tracks. Fast forward to Aarammaus, which came out with the Atrubi trial, uh, attribute trial in 2024, which was another stabilizer which was shown to be beneficial for cardiomyopathy, uh, from transthyretin amyloidosis. And then vitriarran is a silencer, so a different mechanism. If we think back again to sort of the making of this protein in the liver, it's a silencing RNA that basically shuts off the development of this protein, so it doesn't happen anymore. Um, and that has been shown to be beneficial for polyneuropathy for many years, so we've been using that for a while for polyneuropathy. But now, in addition, after the Helios-B trial came out in 2025, so just last year, we now have evidence that this can be helpful for both cardiomyopathy and polyneuropathy. Um, so, you know, great data that we have coming out to show us that we now have treatments for these patients. There's a lot of unknowns sort of in the amyloid world right now. What should you reach for first? Does it help to use both of these agents? Is one better than the other? How do you monitor if you're treating them? Um, can we prevent this from occurring in patients who are maybe gene positive? Uh, there's a lot of next steps, some of which we're actually participating in these trials. There's the CRISPR Cas 9 trial, which is basically a permanent silencer that shuts off the gene permanently with one sort of go around, so a pretty neat way to sort of stop things that tracks permanently. And then there's depleter trials which we are participating in which are monoclonal antibodies that go in and mop up all the amyloid and try to get rid of it. So I'll briefly just go through HTML be done after this, um, but hypertrophic cardiomyopathy is an unexplained, uh, thickness in the wall greater than 1.5 centimeters. It's, uh, commonly thought of as an inherited issue about 60 to 70% of the time. It's inherited in an autosomal dominant pattern. And it's actually more prevalent than maybe we would have thought back in medical school. About 1 in 200 or 1 in 500 patients have this globally, so you'll certainly see this plenty in your clinic or at least maybe someone that is related to somebody that has HCM, which we'll talk about as well. But you can see in the bottom left slide, the H&E slides showing what happens. It's basically this myocyte disarray where they all get out of their nice little lattice formation and start to cause issues. Um, so there's different ways in terms of how we think about managing this. Historically speaking, it was some drug like beta blockers or calcium channel blockers to slow things down, to cause negative ionotropy, or cause the heart to not squeeze too much so that you don't have outflow tract obstruction, which is the driver of symptoms for a lot of these patients. Uh, we'll talk a lot about, hey, you know, don't get dehydrated, avoid hot tubs, stay. You know, make sure you always have bottles of water because when they get dehydrated, they're going to have more obstruction out of their outflow tract. They can have a lot of arrhythmias, both atrial, things like Afib or ventricular, things like VTC or VFib. So you always have to assess sudden cardiac death risk. You don't want your young patient to drop dead on the soccer pitch, so you have to figure out who is going to be at risk of that, and there are score calculators for that to help us. There's other disease modifying therapies we have for patients, more so with Hoche than with HCM, but we'll see in the next few years if there'll be more to talk about non-obstructive HCM. But there are the medications like Camzos, which is a myosin inhibitor, which basically decreases the squeeze of the heart to make it not obstruct too much, and there's more permanent things like myectomies or alcohol septal ablations, which have been around, been around longer. But certainly these patients need familial screening, as you saw, it was something that's commonly inherited. Um, what does that look like? Well, you know, we do gene testing on all of our patients. Um, if the patient who has disease is gene positive and the family member is gene negative, well, you don't have to worry about screening that family member. So, you know, you'll certainly get a lot of family members come to your door asking, what do I need to do? Most of the time the answer is an ECG and an echo and some form of genetic testing is usually all that is required, but this, um, you know, there's also intervals in terms of how frequently we monitor them. If the patient was gene positive and the family is gene positive, well, you're looking at about every, uh, 2 to 3 years or so for that type of patient. If the patient is gene negative, well then you're looking about every 3 to 5 years doing this type of testing, OK? So there's a lot to unpack there, a lot more to talk, but all these are talks. Itself and I just want to sort of bring those two entities up. I stole this from Doctor Kittleson, but I think we'll see updates in the next couple of years in terms of what HEF PE guidelines will look like. I think, you know, in the top Class one recommendations for SGLT-2 inhibitors and MRAs in certain individuals, you're gonna see GLPs be used more regularly, um, obviously diuresing them, and in certain individuals you're gonna be adding things like REs and ARBs when their EF is a little bit low and they have, uh, some hypertension. So HefPf is now the more predominant version of heart failure. It's a clinical diagnosis. They have the signs and symptoms of heart failure. They have a normal EF EF and some version of elevated left ventricular filling pressures which you might have to perturb the system for. We now have pillars for this, and we need to always rule out other entities which may be present. Thank you. Published June 30, 2026 Created by Related Presenters Tim Jordan, MD
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