John McMurray, MBChB: For heart failure with preserved ejection fraction [HFpEF], it has been a real challenge to find an effective treatment. There are probably many reasons behind that. It may be more than 1 syndrome, or these patients may in fact be several distinct groups of patients, one of which I have already mentioned: people with midrange or mildly reduced ejection fraction. Those patients may be more like patients with heart failure with reduced ejection fraction [HFrEF], but for the remainder of patients with HFpEF, those who have a normal ejection fraction, they may have been using the wrong treatments.

What we’ve generally done is that we’ve tried the treatments that have worked in HFrEF to see if they work in HFpEF, but why should they? We may have been studying the wrong treatments. These are also difficult patients to study in clinical trials because they are elderly. They have many comorbidities. Their hospital admission rates and their mortality are often driven as much by their comorbidity as by heart failure. For example, many of these patients, in fact 30% to 40% of them, don’t die from heart failure; they die from other things such as cancer.

Firstly, it’s quite a challenge to identify treatments that might work because we’re not sure what the pathophysiological drivers of HFpEF are. Secondly, it has been challenging to determine whether these patients are all the same and whether 1 treatment would be appropriate for most of them, or if we need very distinct treatments for distinct subgroups or distinct phenotypes. We’re all struggling to decide at the moment.

Jaime Murillo, MD: What kind of challenges and outcomes have we seen? No. 1, we have certainly made progress in terms of preventing readmission in heart failure. I don’t think it’s there yet. It’s not where we want to see it. Whether we’re going to reach 0% is probably unlikely and unrealistic. Nonetheless, we still have more opportunity to decrease the readmission rate. We have made progress but not to the point where we’d feel like we can call that a success.

For challenges, you name it. We could talk for a long time about challenges, starting with the clinical challenges: the comorbidities. There is also a bigger portion of the challenges that we probably have not thoughtfully and adequately addressed, which is all the social determinants of health associated with heart failure. I know you’ve read about it. Everybody knows about it, but we’re still short of meeting that challenge.

We know that many people lack social support, which is important. We don’t know whether they are taking their medications at home. We don’t know how often they’ve been assessed for progression or exacerbation of heart failure. We don’t know whether they have transportation to their appointments. We don’t know whether they have enough money to pay for the medications. We don’t know whether they’re eating properly, so that they won’t have exacerbation of heart failure.

There are a variety of challenges, and that’s the beauty of it, if you could call it that, when it comes to heart failure. You cannot say that it is a clinical disease; this becomes more of a social, economic, clinical, personal disease. I know I’m throwing out a lot of names there, but that gives you an idea of the massive challenge that we have in front of us.