Dr Clyde Yancy: Heart Failure With Preserved Ejection Fraction Is Not One Disease

Heart failure is clearly syndromic, with several phenotypes—cardiopulmonary, cardiorenal, cardiometabolic—so it will remain challenging to reconcile patient to therapy until we can begin to study these unique phenotypes and a priori identify them, stated Clyde W. Yancy, MD, MSc, professor of medicine, chief of cardiology, and vice dean for diversity and inclusion at Northwestern University’s Feinberg School of Medicine.

Yancy presented “Evolving Understanding & Therapeutic Role of SGLT2i and ARNI in 3 Heart Failure Phenotypes: HFrEF, HFiEF & HFpEF” on day 1 of ACC.21.

Transcript

Why have treatments for heart failure with preserved ejection fraction been so elusive?

Because as you begin to think about the most important new therapies for heart failure—the ARNI [angiotensin receptor neprilysin inhibitor] compound and the SGLT2 [sodium-glucose cotransporter-2] inhibitor—we can exercise the opportunity to position these new drugs in which of those 3 phenotypes where there might be evidence of benefit.

Let's start with the ARNI compound. We know for certain, let me emphasize for certain, the ARNI compound is appropriate for reduced ejection fraction heart failure. Well, we also have a very intriguing piece of data and a very important prespecified secondary analysis from PARAGON-HF. The investigators brought forth very important information.

For those patients with symptomatic heart failure with an ejection fraction less than 57%, there was clear evidence of the benefit from the ARNI compound. Now, this was not a prospectively powered subgroup. It was a prespecified analysis, so it is at least suggestive of benefit and gives us kind of a fill-in-the-blank for that intermediate-range ejection fraction.

Now to extend the response as to why we’ve had difficulty finding agents for heart failure with preserved ejection fraction—understanding that we cannot yet place the ARNI compound in that space because the clinical trial was neutral—the reason we've had difficulties is that we know that heart failure with preserved ejection fraction is not one disease, it’s not one syndrome, because heart failure clearly is syndromic. It’s probably several different phenotypes. One is cardiopulmonary, one is cardiorenal, one that we typically see often in the office is cardiometabolic. And so until we can begin to study the unique phenotypes and have a way of a priori identifying the phenotypes, it will continue to be a challenge to reconcile how best patients will respond to individual therapies.

So we're still on the elusive search for that agent that is, without question, effective in all-comers with heart failure with preserved ejection fraction. Previously, I would have said I didn't think was possible. But given the traction we've seen what the sodium-glucose cotransporter-2 inhibitors and knowing that a trial is ongoing, looking at the use of the SGLT2 inhibitor in heart failure with preserved ejection fraction, it might happen. And importantly, the answer to that question using empagliflozin will be available later in calendar year 2021. That could be a breakthrough if that’s positive.