The HFpEF Paradigm: Approach to Diagnosis with Dr. Sanjeeb Bhattacharya

Podcast Transcript

Dr Brateanu: 

Welcome to the Medicine Grand Rounders Podcast, a platform dedicated to exploring key topics in internal medicine. Highly relevant to the medical community. This podcast is made possible through the generous support of a grant from the Cleveland Clinic Education Institute. However, the views and opinions expressed here are those of the speakers and do not necessarily reflect the official position of the Cleveland Clinic. Each episode brings together world class experts and distinguished physicians from Cleveland Clinic to share their knowledge, experience and perspectives on issues that impact healthcare professionals and patient care. Our discussions aim to promote learning, advance professional development and inspire meaningful conversations with the medical community. Today's episode is hosted by Dr. Nitu Kataria, Internal Medicine Physician at the Cleveland Clinic, and me, Dr. Andrei Brateanu also in Internal medicine. We invite you to join us as we delve into today's thought-provoking topic.

Yasmine:

Hi, my name is Yasmine Al Ghul, and I'm one of the internal medicine PGY3s here at the Cleveland Clinic. Today I'm excited to be joined by Dr. Sean Bhattacharya, Director of the HFpEF Clinic here at the clinic to walk us through a few cases regarding the diagnosis and management of HFpFF. Thank you, Dr. Bhattacharya, for joining us.

Dr. Bhattacharya:

Appreciate it. Excited to be on

Yasmine:

Today we will be discussing a few cases that go through the typical presentation of HFpEF, atypical presentation of HFpEF, and then the presentation of something called a HFpEF masquerader. We'll walk through the diagnosis as well as the management. 
Our first case is a 66-year-old female coming into see her PCP for shortness of breath on exertion for the last six months. Her medical history includes well controlled type 2 diabetes, obesity with a BMI of 32 and atrial fibrillation for which she's on a blood thinner. Workup thus far has revealed normal PFTs, unremarkable chest x ray, normal thyroid function and normal blood counts. Her cardiac workup shows an EKG with rate-controlled A fib, an NTproBNP of 400 and an echo with an EF of 56% and grade 2 diastolic dysfunction. Her PCP is suspicious for HFpEF. 
Can you walk us through the typical HFpEF presentation and whether we have enough information to diagnose HFpEF at this time?

Dr. Bhattacharya:

Yeah, this is a great case. One of the clear-cut kind of HFPEF patients may present like this. So we have HFPEF patients who are mostly older adults over the age of 65, predilection for women's sex, especially postmenopausal with known risk factors such as obesity, hypertension, atrial fibrillation and diabetes. You know the initial presentation for HFpEF typically includes dyspnea on exertion, may have signs of bendopnea or shortness of breath bending over. In more advanced cases you'll see them presenting with overt volume overload and dyspnea at rest. The initial workup for HFpEF should include a detailed history and physical exam of course, and a thorough assessment for other causes of dyspnea which was done in this case with PFTs and thyroid function etc. The cardiac workup should include things like EKG, NTproBNP or BNP, whichever is available at your institution and a resting transthoracic echocardiogram to understand the physiology underlying the patient. A typical patient with HFpEF would be expected to have signs of diastolic dysfunction at rest with echo. That's typically the stage diastolic dysfunction we see, but other signs as well, including ejection fraction greater than 50%, dilated left atrium or enlarged left atrium, maybe signs of hypertrophy of the walls of the myocardium and possibly estimated elevation of left atrial pressure or LVEDP on echocardiogram. There are some advanced things that we take a look at in cardiology such as E’/e’ prime ratio which has been important in trying to predict left atrial pressure. It's not an exact science but one of the things we look at when we risk stratify patients with HFpEF.

Yasmine:

Thank you so much for walking us through the typical presentation of HFpEF as well as the risk factors and things to look for on diagnostic testing. Our next patient is a 71-year-old black male who is also presenting with dyspnea on exertion in the context of long-standing obesity, hypertension and CKD3. His workup is negative for non-cardiac causes of dyspnea. His resting echo transthoracic echo also shows a normal EF. However, he does not have any diastolic dysfunction noted in the report, and his NTproBNP is normal. Does this rule out HFpEF? and if not, is there anything we can do to risk stratify this patient for having HFpEF or to work him up further?

Dr. Bhattacharya:

Yeah, this is a great example of a case that's not so clear cut, and we see this a lot in our HFpEF clinics, but can be seen more frequently in internal medicine or family practice clinics as well as our pulmonary colleagues’ clinics for dyspnea on exertion. 

In cases where patients have obesity, you can have a falsely normal or lower NTproBNP than expected. So, it does not a 100% rule out in this case that the patient has underlying HFpEF. So even though the preliminary workup is negative, there are a couple of scoring systems that we've used to help risk stratify to see if there's any concern for HFpEF or may need other kind of diagnostic workup. One is using the HF2PEF score out of the Mayo Clinic, and the other one is from the ESC looking at HFA-PEFF score. Both look at similar but more detailed kind of things in different ways. The H2FPEF score is very easy in terms of looking at simple risk factors, including BMI, degree of hypertension, meaning how many medications they're using, atrial fibrillation, age and things like that to sort of create a risk score. And if you have 5, which each are weighted a little bit differently, including the echocardiographic findings like E’/e’ and RVSP. But once you have a score greater than 4, the likelihood of having HFpEF along with the diagnosis becomes very high. The HFA-PEFF score is a little more detailed, looking at left atrial volumes, looking at NT Pro BNP and atrial fibrillation and in sinus rhythm, and more echocardiographic kind of findings, which can be a little more tough for a primary care doctor to kind of look at. But does risk stratify very well to see who has a high index of suspicion for HFpEF or who needs other testing, which is typically more advanced exercise testing, where you're looking at something like a diastolic stress test with echocardiogram at rest and with exercise, or more invasively, an invasive right heart cath with exercise, where you're getting hemodynamics at rest and then subsequently with exercise, with, you know, the more advanced testing being an invasive cardiopulmonary exercise test, where the dyspnea on exertion is a little hard to kind of figure out what is coming from what. If there's a lung component, muscular component, or cardiac component. The invasive cardiopulmonary exercise test gives a very detailed assessment of all three of those systems.

Yasmine:

Thank you, Dr. Bhattacharya, for walking us through that atypical HFpEF presentation. So, it sounds like these scoring systems are relatively simple for the general practitioner to use and that if we're hitting a score that's within that intermediate range where we can't really rule in or rule out HFpEF, it'd be best to refer to cardiology for some more advanced testing.

Dr Bhattacharya:

Yeah, in general, we as cardiologists love seeing these patients, or at least I love seeing these patients. You can always refer, but advanced testing is always important, especially because most of these patients have symptoms when walking or are active versus at rest. So dynamic exercise studies are more important than just resting studies. And in the Cath lab, when we do a lot of these right heart caths, we can do provocative maneuvers outside of exercise in case they do have orthopedic problems. Not everyone's able to ride a bike or things like that for us. So doing things like leg lifts or saline challenges have been helpful to unmask HFpEF, especially if their resting pulmonary capillary wedge pressure is normal, which is our estimation for left atrial pressure.

Yasmine:

This brings us to our final case, our middle-aged patient with dyspnea on exertion, hypertension and bilateral carpal tunnel. Her TTE also reveals a preserved EF with diastolic dysfunction, LV hypertrophy and a strain pattern that is apical sparing. Her PCP orders an amyloid workup, and the patient is later confirmed to have cardiac amyloidosis on endomyocardial biopsy. Would this patient be classified as having HFpEF and would the treatment differ from conventional HFpEF treatment?

Dr. Bhattacharya:

Yeah, this is a very important case in that this has a patient who does have HFpEF. When you think about heart failure with preserved ejection fraction, it's signs and symptoms of heart failure in the setting of an ejection fraction greater than 50%. So technically, yes, but going deeper into this case, it's important to understand that there are certain disease processes which have independent treatment along with the treatments that we use for HFpEF as well. So, in cardiac amyloidosis, one of the “masqueraders” for HFpEF, it's important because we have disease modifying agents to treat these patients.

So, if we break down what we heard in this case, you mentioned things like abnormal strain pattern, which is a way that we look at myocardial myocyte stretch in respect to each other on an echocardiogram. If we see certain patterns, like apical sparing or the ‘cherry on top’ on the bullseye scoring sheet, that gives us an idea that this patient might have cardiac amyloid. Especially if you're seeing other signs like significant left ventricular hypertrophy, things like aortic valve thickening, mitral valve thickening, things like that. It should have a heightened awareness for these disease processes. And for amyloid, initially thought to be very rare, this is something we're diagnosing more and more now because the testing is so much easier. Looking at nuclear scans and blood tests to really elucidate which one we're talking about in terms of amyloid in the heart. So, a very important point to pick up these masqueraders such as cardiac amyloid, also hypertrophic cardiomyopathy, other restrictive cardiomyopathies or infiltrative cardiomyopathies as well. In terms of treatment, I do treat these very similar to my HFpEF patients. So, they're typically on SGLT2 inhibitors and MRAs. However, the data is very small. Looking at specifically amyloid patients, we know they're safe and does help with decongestion, cardiorenal syndrome, etcetera. But putting them on disease modifying therapies such as silencers are going to be important to help change the trajectory of their actual disease pattern.

Yasmine:

Okay, thank you for walking us through, you know, the importance of catching those masqueraders and still treating HFpEF, while also making sure we're treating, you know, the other treatable condition that's causing the HFpEF. You mentioned MRAs and SGLT2 inhibitors as treatment for HFpEF. Can you walk us through some of the trials that kind of establish these therapies for management of HFpEF?

Dr. Bhattacharya:

Yeah. So, until recently, I think everyone's been very frustrated with the treatment of HFpEF. Most of the clinical trials we have in terms of looking at beta blockers, ACE inhibitors, ARBs have been negative. And I think that we took a disease entity that was different than heart failure with reduced ejection fraction and we tried to see if the normal therapies for HFrEF were applicable to HFpEF. And I think as we started seeing more negative clinical trials, I think this was exciting in that we had to go back and really understand what was going on in the disease process and specifically seeing how this is very different than HFrEF. It wasn't until SGLT2 inhibitors with dapagliflozin and empagliflozin would deliver an EMPEROR-preserve where we actually saw therapy that can help reduce hospitalizations and improve quality of life, looking at KCCQ questionnaires. So, until those trials, everything has been very up in the air. When you, you look at MRA data initially with TOPCAT, the overall clinical trial was negative, looking at reduction in hospitalizations, mortality. But we saw regional differences based on the Americas, north and Central and South America versus the Georgias and Russia. And there started to see that there were differences in how patients were presenting with dyspneal on exertion and how we categorize HFpEF. Now with fine arts looking at finerenone, that kind of redid TOPCAT showing an improvement in hospitalizations, CKD, etc. So, I think the MRA data is very positive, but overall, nothing has really moved the needle on mortality. So, I think as we go forward, I think we're more excited as we kind of do HFpEF phenotyping, knowing that these patients are not the same in terms of one to another. So, looking at agents like GLP1s for our obesity, CKD patients; looking at interatrial shunts for patients with left atrial hypertension with exercise. You know, know these are exciting clinical trials undergoing now to really see how we can help patients and really hone in on what type of HFpEF presentation they're actually coming in with.

Yasmine:

That's really interesting. So maybe in the future we'll see treatment kind of tailored more towards the specific phenotype or like small differences between our HFpEF patients. Is there anything on the horizon or some new and upcoming treatments that we're excited about in HFpEF treatment?

Dr. Bhattacharya:

Yeah. So, the GLP1s probably have the newest data looking at STEP-HFpEF with Semaglutide and then SUMMIT trial with Tirzepatide. Looking at improvements in functional ability, able to walk in terms of six-minute walk, testing improvements in KCCQ, which can be difficult to use that as a primary endpoint because we saw improvements in KCCQ in the placebo arm too, but also reduction in degree of diuretic adjustments, heart failure, hospitalizations and things like that. So, I think GLP1s for the obese patient, whether you have diabetes or non-diabetes, can be very helpful in controlling HFpEF, improving symptoms and quality of life, which I think is very important in this patient population. When we look on the horizon, I think we're looking at other kind of manifestations. So, devices are coming into play. Interatrial shunts where initial trials have been negative, but looking at a very specific group of exercise physiology with HFpEF is being studied now, whether you look at the RESPONDER-HF or Lay trials going on now looking at things like myosin inhibitors which have been a breakthrough for hypertrophic cardiomyopathy, looking at in patients with higher ejection fractions with HFpEF and things looking at metabolic activators which really target adipose tissue versus non-specific weight loss, which we do see with the GLP1s where you actually lose fat but you also lose muscle mass as well. So other things along the way are immune modulators, looking at anti-inflammatory medications. So, I think the, the realm of therapies that are being tested are just very exciting in the HFpEF realm. So, we'll have to see how all of these bore out when they are in their large clinical trials. So hopefully in the next few years, you know, SGLT2s, GLP1s now won't be the only therapies we have for this patient population.

Yasmine: 

Well, thank you so much for walking us through all of these great clinical cases and thank you so much for walking us through kind of treatment and what's upcoming. As a HFpEF expert, can you give us three clinical pearls for the general practitioner for suspecting and diagnosing HFpEF?

Dr. Bhattacharya:

Yeah, I think number one, primary care sees these patients. So, I think whatever we can do to make this more recognizable is important. So, these simple risk scoring tools like H2FPEF, which I think is super simple to use versus HFA-PEFF can be very easy which can be done in clinic. You can identify these patients or at least say that there might be a high incident suspicion for HFpEF causing the dyspneal exertion for these patients.

For Pearl 2, the big thing is not to be encouraged or dissuaded for more advanced testing if you think things are coming back normal. So normal NTproBNPs in the obese patients are very difficult to really interpret. Resting echocardiograms may not show many abnormalities, but still when you actually exercise patients you can see that. So, I think it's really important to have that kind of spider man sense up to know that, you know, even though you think that the testing seems reasonable or normal, not to just stop there and go forward and try to dig a little bit deeper in how these patients are really short of breath. And that's where some of these specialty clinics like HFpEF clinic and things like that can be helpful because we help do that for you. 
 And then Pearl 3, I think most importantly, as you highlighted in your last case, masqueraders are super important to identify because disease modifying agents are here. So, things like cardiac amyloidosis can be treated on a disease level aside from diuretic use, SGLT2 inhibitor use and things like that. Hypertrophic cardiomyopathy as well. And I know that the obstructives have new disease modifying agents like Mavacamten and other myosin inhibitors. So, I think it's super important to keep in mind that just diagnosing HFpEF doesn't 100% give you the full picture of what's going on. And if there's something that doesn't fit, absolutely send to a cardiologist, send to our heart failure colleagues here and we can help kind of dig a little bit deeper to see what might be going on.

Yasmine: 

Well, this is so much fun, and I think we've all learned a lot about HFpEF. Thank you so much Dr. Bhattacharya.

Dr. Bhattacharya:

Anytime. Happy to be here.

Dr. Kataria:

To our listeners, thank you for joining us on this deep dive into this important topic. We hope you found this episode both educational and engaging. On behalf of the team, thank you to our special guests who joined us today. Thank you also to the Cleveland Clinic Education Institute for the educational support of this project. Until next time, please enjoy this and future podcasts from the Cleveland Clinic Medicine Grand Rounders.