Ileana L. Piña, MD, MPH


May 18, 2023

This transcript has been edited for clarity.

Hello. I'm Ileana Piña. I'm the quality officer for cardiovascular line at Thomas Jefferson University in Philadelphia, and this is my blog.

I really wanted to do this blog because there are two papers that I want to talk to you about. I am really impressed at how well written they are and how well structured they are. They both have to do with heart failure with preserved ejection fraction (HFpEF).

You have heard me talk about the growing number of patients with HFpEF. Yet, it is a difficult diagnosis. It's much easier to diagnose HF with reduced EF (HFrEF) because the EF is abnormal and the patient usually has a history, whether it's hypertension or myocardial infarction. This is different, and I think most of these patients are probably sitting in the primary care office.

In the primary care office, they may look like patients with diabetes. They may look like patients with obesity, thinking that they're short of breath because of their obesity. They may be looked at as the hypertensive variety. Yet, it's never brought out that this is really HFpEF.

American College of Cardiology (ACC) Expert Consensus Decision Pathway

This paper is actually a consensus document by experts explaining why we are seeing more of this, how to diagnose it, and what things mimic HFpEF but are not, in fact, HFpEF and may have other causation.

I think it's a beautiful roadmap for any clinician to look at carefully, and please look at each and every item. The figures are excellent. There were figures with these Venn-like diagrams that show how the primary care specialist really will be key here in realizing that the symptoms of shortness of breath with exertion could, in fact, be HFpEF, and that you should go ahead and get that N-terminal pro B-type natriuretic peptide (NT-proBNP) because it's going to help you with the diagnosis.

Of course, even more importantly, once you make that diagnosis, once you bring it all together, what drugs are you going to use? There's another table that mimics the 2022 guidelines but tells you to always think of the sodium-glucose cotransporter 2 (SGLT2) inhibitors first. These drugs really have revolutionized the care of HFpEF. Then, you can add other things like the mineralocorticoid receptor antagonist; 25 mg a day is what's recommended.

Then you may want to add either sacubitril valsartan, where I don't think the data are as strong because patients with a mean EF > 57 do not respond as well, or maybe an angiotensin receptor blocker like candesartan, which was actually studied in the HFpEF population.

I also want you to remember that the definition for EF has changed, and many of these earlier trials looked at over 40% or over 45%. In our new definition of HF, true HFpEF begins at 50% or higher. The first important distinction to be made is what EF are you looking at in this particular patient, and how are you going to fit that in with the data that we have from the studies?

Certainly, we have the SGLT2 inhibitors. Right now, we have empagliflozin and dapagliflozin, and the guidelines really use it as a generic format. It's an SGLT2. They don't specify whether you want to use canagliflozin or sotagliflozin. There are many others coming out other than empagliflozin or dapagliflozin, which is what we have now in most of the formularies. They are approved for this, and the data are really solid and have been incredibly consistent.

Inflammation and Obesity

Let me backtrack a little bit about the diagnosis. There's a heavy emphasis right now on obesity, and obesity linking to inflammation, and inflammation being very much at the core of the development of the HFpEF syndrome. Inflammation, which includes markers like interleukin (IL)–6, IL-1, and C-reactive protein, which we've heard so much about in the coronary world where we use statins. Statins have anti-inflammatory properties in the patients with coronary disease.

It's a little bit different here. We haven't really tagged inflammation as a target, but I think we're starting to realize that maybe that's where the SGLT2 inhibitors are working. Take a look at obesity because it's a very important comorbidity in these patients. Try to rule out whether they have coronary disease. Are their symptoms related to coronary disease? Is there sleep apnea? Do these patients have diabetes?

The paper really highlights the importance of comorbidities. You may have a patient that has all the above. They may be a diabetic who already is obese or overweight, at least, who has had hypertension for a while. Now you've got this confluence of these three comorbidities surrounding this diagnosis.

Finally, how are you going to detect what happens when the patient exercises? HFpEF symptoms classically include shortness of breath, fatigue, or both with activity. As long as a patient is sitting, maybe their left atrial pressures look normal or nearly normal. But, as soon as they start doing an activity, those pressures go up very high. What about an exercise echocardiogram that can detect measures of pressure in the left atrium while the patient is exercising?

Again, don't forget to use NT-proBNP because that is part of the definition. Other than the symptoms of shortness of breath with activity, you have to have at least one sign. It may be an elevated NT-proBNP or congestion. Can you detect congestion: high left atrial pressures, high pulmonary pressures, or the need for a diuretic? These are all congestion signs that need to go along with it.

Let me remind you that the NT-proBNP levels in HFpEF are usually lower than in HFrEF. You can use the patient as their own baseline; if this is a new patient that you're seeing in the office, get that NT-proBNP early while you're seeing them with those symptoms and then track them.

If you're doing a therapy that's going to be beneficial, I bet that NT-proBNP will go down, and it should give you the signal that you're going in the right direction. See how the patient feels as the NT-proBNP goes down.

This is really a clinical challenge. We're going to be seeing more of these patients. The population does have a large amount of obesity out there. There are many diabetics. It's becoming highly prevalent. I think, no matter what specialty you're in, you're going to be seeing more of these patients.

This was published in the Journal of the American College of Cardiology with a companion paper, written by Dr Barry Borlaug from the Mayo Clinic, also beautifully defining the physiology and talking about exercise testing in this population.

There are also some thoughts about a grading system. The symptoms might have a grade and then next to that could be the body mass index and the NT-proBNP. He talks about two different grading systems or a formula to give you a number that detects or doesn't detect HFpEF.

Thank you for listening today. I hope you read both papers. I really like them. I'm very enthusiastic about both.

This is Ileana Piña signing off. Thank you for joining me today.

Ileana L. Piña, MD, MPH, is a heart failure and cardiac transplantation expert. She serves as an advisor/consultant to the FDA's Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982. Originally from Havana, Cuba, she is passionate about enrolling more women and minorities in clinical trials. She also enjoys cooking and taking spin classes.

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