Unmet Needs in Heart Failure

James Januzzi, MD: We've talked all about heart failure with reduced ejection fraction [HFrEF], but as we have spoken about, there are different classifications for heart failure, including mildly reduced [HFmrEF] and preserved EF [HFpEF] that we've essentially ignored. We did talk a bit about how mildly reduced behaves like reduced, and we treat it like reduced. Let's talk about preserved EF heart failure. And Rob, you've been working in this space actually along with Muthiah, so I'm going to go back and forth with you all and get some input on HFpEF as well as mildly reduced ejection fraction. What are the current unmet needs right now, Rob, and in particular, are there new therapeutic developments?

Robert J. Mentz, MD: This is a really important piece to underscore as we see this increasing prevalence of heart failure with preserved ejection fraction, where historically we didn't have key data around evidence-based therapies. The focus historically had been on comorbidity management. But now I would argue we're moving more toward triple therapy considerations, realizing we don't have the same class recommendations. As we look through now with SGLT2 inhibitors, the most recent guidelines prior to the DELIVER program coming out, giving a class 2 recommendation for SGLT2 inhibitors.

James Januzzi, MD: Probably should have been a 1BR, quite frankly. It was a positive single trial.

Robert J. Mentz, MD: I would agree. The top of that list would definitely be SGLT2 inhibitors in HFpEF.

James Januzzi, MD: OK. What about MRIs [magnetic resonance imaging]?

Robert J. Mentz, MD: That's next up. This is also a class 2 recommendation, and the guidelines nicely give a perspective around this, that it seems the benefit may be greater in those with EF on the lower end of this preserved spectrum. Similarly, with ARNI therapy [angiotensin receptor neprilysin inhibitor], as we'll get into it in further detail, following the PARADIGM-HF program in patients with chronic heart failure with EF 45% or greater, we saw narrowly missing the nominal statistical significance, but reducing heart failure hospitalizations in terms of number, which has then led to this class 2 recommendations, but noting as in line with the label now that the benefit may be greater than those with EF below normal.

Transcript edited for clarity