Heart Failure With Preserved Ejection Fraction: Current Status and Future Opportunities - Episode 10

Differences in Standard of Care: HFpEF vs HFrEF

Expert physicians consider how the treatment of patients differ when they have HFpEF versus HFrEF.

Scott D. Solomon, MD: When we think about the standard care in heart failure, we have to make the distinction between HFrEF [heart failure with reduced ejection fraction] and HFpEF [heart failure with preserved ejection fraction] because we have evidence-based therapy for HFrEF, but we simply don’t for heart failure with preserved ejection fraction. There is no standard of care for HFpEF at the moment. What do we do? We treat empirically. We reduce congestion by treating with diuretics. We identify other reasons the patients may have the signs and symptoms that they do. In other words, we would consider alternative diagnoses. We lower blood pressure because it has been shown that lowering blood pressure can reduce the risk of heart failure hospitalizations. We diagnose and treat ischemia. If a patient is having signs and symptoms because of ischemia, we can usually do something about that and treat them. We rate-control patients in atrial fibrillation, and many of us believe that we should even rhythm-control patients in atrial fibrillation, although there are no trial data to demonstrate that yet.

Once we get to that point and have done all of these things, we also want to make sure that our patients don‘t have another disease that can be treated in a different way that is mimicking heart failure with preserved ejection fraction, such as amyloid heart disease or hypertrophic cardiomyopathy. There are emerging therapies for both of these entities now as well. When we then get to the point where we are at the end of our rope, we can consider some of the therapies that have been tested in trials but that are not specifically indicated for heart failure with preserved ejection fraction. Spironolactone has a class 2b indication in the guidelines, and I’ve certainly used spironolactone in some of my patients with heart failure with preserved ejection fraction, particularly in patients who have ejection fractions that are below normal. I’m not sure any of the therapies that we’ve tested so far will be particularly beneficial in patients whose ejection fraction is above what we would consider the normal range around 60%.

John McMurray, MBChB: At this moment at the end of 2020, when we think about HFpEF, we’re probably thinking about individuals with midrange or mildly reduced ejection fraction. We may need to start treating them with the therapies that we use in patients with heart failure with reduced ejection fraction. For the remainder of those HFpEF, or patients with essentially normal ejection fraction who have signs and symptoms of heart failure, the treatment is largely empirical at the moment. We are treating their congestion with diuretics, and we’re treating their comorbidities with drugs. It could be, for example, their diabetes, their chronic kidney disease, or their anemia. We are waiting for the ongoing trials. We haven’t given up on trying to find effective therapies in those patients, so there are 2 large trials underway with sodium-glucose cotransporter-2 [SGLT2] inhibitors. Those will report next year.

There is also a large trial that’s just started with a new mineralocorticoid receptor antagonist called finerenone, so we haven’t given up hope of finding new treatments. But at the moment for many of those patients, it’s completely empirical, largely using treatments to relieve symptoms rather than necessarily improve outcomes.

Jaime Murillo, MD: Everybody used to think of heart failure as a patient who has an enlarged heart that is weak and unable to pump, and that was a traditional thought until the 1990s. Interestingly, the concept of preserved heart failure means that the heart is not necessarily enlarged: it squeezes the blood out of the heart well, but it’s stiff. It doesn’t relax: it has no elasticity and no ability to open up to get more blood. At the end, you end up with a chamber size that is relatively small, so the blood comes in from the lungs with oxygen, it fills in too quickly, and there is not enough space, so the blood is getting pushed backward toward the upper chambers of the heart and the lungs. That’s called heart failure with preserved ejection fraction.

In the 1990s, we started to develop some echocardiographic technologies to be able to assess how stiff the heart was. We started doing the Tissue Doppler imaging. I don’t want to get too technical, but even 20 years ago, I remember many cardiologists felt that heart failure with preserved ejection fraction didn’t exist. Back then, it was called diastolic heart failure, and they were kind of mocking that. Over time, people proved that this was a huge part of the patients with heart failure who we were missing. As of today, 50% of the people with heart failure have a normal pumping heart. It’s called diastolic heart failure with preserved ejection fraction, and 50% are those who have a weakened heart that’s called heart failure with reduced ejection fraction.

The question is about whether these populations are managed differently, meaning those with reduced ejection fraction and those with preserved ejection fraction. The reality is that, when it comes to designing programs, we’re not there yet. Individually, the answer is yes, but if you talk to cardiologists and say, “Mr. Smith has reduced ejection fraction, so I’m going to make sure that they are not having volume overload,” so they put the patient on diuretics, they put them on β-blockers, maybe Coreg [carvedilol], and they put the patient on an ACE [angiotensin-converting enzyme] inhibitor. They work them up on renal function and blood pressure, and that’s the usual. They could use other medications like spironolactone and so on.

An area where I’m not sure patients are well served is in treating the underlying cause. We sometimes miss the fact that they may benefit from revascularization if they have ischemic cardiomyopathy or if they may have valvular disease. It’s sometimes difficult to determine whether the valvular disease was secondary to the dilation of the heart or what’s causing the dilated ventricle. That’s more the traditional focus in heart failure. Then there is the practice of saying, “Call me if you notice that your weight starts going up 2 or 3 pounds every day” and so on. That population is very sick, they have a lot of comorbidities, they tend to decompensate slower, and they tend to stay in the hospital much longer. It is difficult to find that balance between getting rid of fluid and not drying them out too much without affecting their kidney function.

For the preserved ejection fraction, I don’t want to get too clinical, but this is the group for whom there is still some mystery. That may not be the appropriate word, but let’s just say that we don’t have a good handle on how to address preserved ejection fraction. The treatment with diuretics cannot be as aggressive with these patients because their main problem is not necessarily volume overload; it’s the fact that their ventricle is relatively small compared to the amount of volume. They decompensate very quickly, but at the same time, they can compensate fairly quickly as well. If we’re too aggressive with diuretics, for instance, we’re now drying the kidneys, and they end up with acute kidney failure such that we need to rehydrate, and it becomes us chasing this catch-22 cycle.

The other part where we don’t do a good job is trying to figure out what the underlying cause of preserved ejection fraction is, whether there’s hypertensive heart disease, whether there’s amyloid, whether it’s a secondary cause of the condition in patients who have end-stage renal disease, whether it’s arrhythmias, whether they have some hypertrophic cardiomyopathy, or some other causes of some thickness or fibrosis of the muscle of the heart. In reality, it’s more of a 1:1, but as a whole program, that’s my point: we don’t have tailored programs designed to treat them differently even within those 2 large categories. I’m sure there will be institutions making an effort in making that differentiation, but in general, I would argue that we still have an opportunity to get better at it.