Bob Underwood, MD (Host): Welcome to Advancing Worsening Heart Failure Treatment, Exploring Cutting Edge Therapies and Addressing Disparities. I'm Dr. Bob Underwood. I'm joined today by two of my esteemed colleagues, Dr. Deepak Bhatt, Director of Mount Sinai Heart and the Inaugural Dr. Valentin Fuster Professor of Cardiovascular Medicine; and Dr. Erin Michos, Director of Women's Cardiovascular Health Research, Associate Director of Preventive Cardiology at Johns Hopkins University School of Medicine, Co-Director of the Impact Center at Johns Hopkins University, and Co-Editor in Chief of the American Journal of Preventive Cardiology. For full, relevant financial disclosure information, please see iridiumce.com/hf. This educational activity is supported by an independent educational grant from Merck, Sharp, and Dohme. We'd like to thank them for their support of this initiative. The learning objective for this program is to describe the diagnosis and prognosis of worsening heart failure. So, welcome to both of you. Thanks for being on.

Erin Michos, MD: Thank you for having us.

Deepak Bhatt, MD: Great to be with you.

Host: Yeah, absolutely. So Dr. Bhatt, can you give us some information on the epidemiology of heart failure?

Deepak Bhatt, MD: Well, simply put, the epidemiology of heart failure is that there's a lot of it out there. In the U.S., it depends exactly where you look for estimates, but around 6.7 million or so Americans have heart failure. And there's been an increase of about 700,000 or so cases just in the last five years. So, it's, as they say, an epidemic.

Host: Yeah, absolutely. And as an emergency physician, you know, we see it every day. This is very, very common in terms of what the patients present with. So Dr. Michos, can you describe the disease progression of heart failure? And at what point are patients diagnosed with worsening heart failure?

Erin Michos, MD: Great question. I mean, heart failure is a chronic condition with, you know, periods of instability. I first just wanted to review the stages of heart failure for framework. So, stage A and stage B are your asymptomatic stages. So, stage A means you're at risk for heart failure. You have risk factors. Stage B is pre-heart failure where there's evidence of structural heart disease or evidence of increased filling pressures. But stage C is when you actually have symptomatic heart failure with current or previous signs of clinical heart failure. And then, stage D is your advanced heart failure. So for clinically evident heart failure, about half is heart failure with preserved ejection fraction and half is heart failure with reduced ejection fraction. So, this could be a disease that's stable for months to many years, but interrupted by periods of worsening symptoms despite optimal treatment, and it can progress to really advanced stages of heart. And these periods of worsening heart failure symptoms what we describe as worsening heart failure.

Host: So Dr. Bhatt, can you help us understand then the prognosis of heart failure and worsening heart failure?

Deepak Bhatt, MD: Sure. The prognosis is actually pretty bad, not to be pessimistic. And there have been a number of improvements in recent years, but a number that's still often quoted is a five-year mortality rate of around 50%. That's worse than many cancers. The prognosis gets even worse once worsening heart failure occurs, about a three-fold increase in mortality, about a six-fold increase in hospitalization. So, it's often a pretty bad cycle when a patient patient has really bad heart failure, gets hospitalized, that itself is an issue, but it also portends badness for the future. Males, as it turns out, are more likely to die from heart failure than females, and rural patients are also more likely to die than urban patients.

Host: So, you know, based on that, how was worsening heart failure commonly diagnosed? So, are there problems with diagnosing worsening heart failure in this particular way?

Deepak Bhatt, MD: Good question. Well, diagnosis of heart failure has some subtlety and complexity to it. In general, I'd say heart failure or worsening heart failure is commonly diagnosed by a need for acute cardiovascular care for symptoms of congestion, including hospitalization, including intravenous diuretics. Like up your alley, patients are also treated in the emergency department, but also as outpatients. There can be variation based on region, different countries. Around the world handle heart failure a little bit differently. Some are more or less comfortable with the outpatient management and so forth. The progression for worsening heart failure can be gradual and includes subclinical symptoms. It can also, of course, be sudden at times and common measures of heart health that are not diagnostic for worsening heart failure include ejection fraction, blood pressure and heart rate. And I'm sure we'll get into some of those controversies in terms of ejection fraction and how good it is or isn't in terms of diagnosing or seeing heart failure.

Host: So, we talked about what are commonly used to diagnose. So, what are some of the new techniques that are available for the diagnosis of worsening heart failure? Dr. Michos, how about you?

Erin Michos, MD: So, you know, heart failure is diagnosed by symptoms, but there can certainly be supportive evidence to support the diagnosis, and one of those is biomarkers. So, biomarkers can help detect worsening heart failure in stable patients. Most commonly, we're thinking about the B-type natriuretic peptides, so BNP or NT-proBNP levels. Of note, the American College of Cardiology, the American Heart Association, also gave a class IIa indication for using natriuretic peptide screening, and patients who are at risk for heart failure and helping identify those who might be at risk for developing clinical symptoms.

There can also be other indirect measures including serum albumin levels, kidney functions, creatinine, transaminase. And notably, we often use imaging techniques, echocardiogram being one of the most common used modality. On echo, you can measure the inferior cava size, diameter and whether it collapses with inspiration. This gives you some estimate about right atrial pressures. You can estimate pulmonary artery pressures with your RVSP. There are echo assessments of left atrial filling pressures. These include things like the E/e' ratio and left atrial volumes. You can also do ultrasound to look for systemic venous congestion of the liver and the kidneys. You can use point-of-care ultrasound, POCUS, to look for B lines in the lungs, which can be a finding of interstitial pulmonary edema. So, we use biomarkers and imaging techniques to support our clinical suspicion of the diagnosis of heart failure or worsening of it.

Host: Yeah, absolutely. And, you know, just to tell you how long I've been doing this, I couldn't remember when BNP was a new test for us to be using in the emergency department. So, Dr. Bhatt, I guess in a future episode, we'll talk about monitoring devices for detecting worsening heart failure as well.

Deepak Bhatt, MD: Yeah, I think it's an exciting topic. And I guess just to whet the audience's appetite, that will be covered in a future episode, but monitoring devices, some invasive, some non-invasive have really changed our management of heart failure, and I think will increase in the future, especially as the technologies blossom, wearables become more prevalent, so a bright future there for a variety of different disease states, including heart failure.

Host: Yeah, I think that there's really just some great things that are coming around with technology and even artificial intelligence being built into some of that technology to help us. So, we're looking forward having further discussions. So Dr. Michos, can you explain why left ventricular injection fraction is important in heart failure?

Erin Michos, MD: Yes. So, first of all, I can just describe the categories now that we're using for heart failure by ejection fraction. So, when we call a heart failure with preserved ejection fraction, generally we're talking about ejection fraction greater or equal to 50%. There's sort of a new category now called mildly reduced mid-range EF of 41 to 49%. And then, there is heart failure with reduced ejection fraction, which is generally an ejection fraction less than 40%. And I will note that studies sometimes use different cut points for these. But if you're looking at roughly the percentage of patients in each category, about 46% are this HEFpEF, about 46% HEFrEF, and about 8% are these heart failure with mid-range ejection fraction.

 Why does it matter? Well, notably, some treatment options for heart failure are dependent on the left ventricular ejection fraction, and we have different recommendations for therapies based on that distinction. You know, there are some sex and gender differences. Female patients tend to more often present with heart failure preserved ejection fraction. More male patients have heart failure with reduced ejection fraction. And then when you look into outcomes, so there are population-based data out there from hospitalized patients that have shown actually similar mortality rates in patients with both HEFpEF and HEFrEF, so similarly bad outcomes.

Now, there are some studies that have suggested some differences with a lower mortality in HEFpEF. There's also some questions about whether HEFpEF was ovoverdiagnosedith an overreliance on maybe echo and maybe not on the clinical symptoms. But there's a lot of studies suggesting, you know, equally poor outcomes for both types of heart failure.

Deepak Bhatt, MD: Yeah, I think there's a lot of HEFrEF out there. There's a lot of HEFpEF out there. We're learning quite a bit about each of those subtypes, as well as the one in between with the mildly reduced or mid-range or sometimes recovering EF. There's just, I think, a lot of new knowledge coming out, even just about the classification of heart failure, which is amazing to me. And I guess, at least in the short and intermediate term, we're going to keep relying on ejection fraction for that categorization, but I wouldn't be surprised if in the future it becomes much more sophisticated. Dr. Underwood mentioned artificial intelligence. I do think that AI is going to be able to provide a lot more insights into images that the human eye can't really see. And I think there'll be much finer categorization of patients, especially those with heart failure with preserved ejection fraction, where it's not just a wastebasket diagnosis, but it's further stratified into whether patients have hypertrophic cardiomyopathy or amyloid or any variety of different disease subtypes that are yet to be defined.

Host: You know, it's really exciting how these things have evolved over time and how we're able to substratify all of these. And, you know, it gets down to the treatment of these individual patients based on all of this information that we're able to glean now that we weren't able to do before. So, anything else you guys would like to add before we close this segment?

Erin Michos, MD: Now, I would just say even with among ejection fraction, there's further subtyping. You know, you can have both ischemic cardiomyopathy and non-ischemic cardiomyopathy. And HEFpEF is really emerging to be a very heterogeneous. And they have different phenotypes such as an obesity phenotype or perhaps a hypertensive phenotype. So, I think we're going to continue to learn a lot more about how to diagnose and treat this challenging entity.

Deepak Bhatt, MD: Yeah, I agree with all Dr. Michos' comments. I might just add that if a patient has worsening heart failure, in particular, if it prompts an urgent visit or a hospitalization, that's really a big deal and oftentimes portends that the patient's starting to fall off a cliff in regards to their heart failure and the trajectory it's going to take.

So, I would say take those hospitalizations seriously. Make sure patients are fully optimized on their medical therapy, if possible, even prior to discharge, assuming they can tolerate polypharmacy prior to discharge and maybe that's one way to make a dent in the epidemic of heart failure.

Host: Yeah, absolutely. Thanks for both of you. We've reached the end of this episode. Dr. Mickos, Dr. Bhatt, thank you so much for this engaging discussion. We'd also like to thank Merck for their support of this program. Be sure to claim your CME credit by filling out the evaluation and the post test. And don't miss the next three episodes of this four-part series. Be sure to follow Iridium on X, facebook, and LinkedIn to see the corresponding MedEd threads. Thanks so much for being with us.