Heart Failure With Preserved Ejection Fraction: Current Status and Future Opportunities - Episode 3

Link Between LVEF, NT-ProBNP and Cardiac Remodeling

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A discussion on the link between LVEF, nT-proBNP, and cardiac remodeling in predicting disease progression.


Scott D. Solomon, MD: It’s important to remember that ejection fraction and natriuretic peptides are different metrics: They measure different things. Ejection fraction is a measure of cardiac function, and natriuretic peptides are essentially a hormone that is released in the setting of increased wall stress. You can have elevated natriuretic peptides in patients with a normal ejection fraction. You can have elevated natriuretic peptides in patients with reduced ejection fraction. You can have relatively low natriuretic peptides in patients with reduced ejection fraction and, of course, in those who are normal as well.

They’re complementary measures in patients with heart failure. It’s particularly important, though, in patients with relatively preserved ejection fraction to assure ourselves that that patient truly has the entity that we call heart failure. It is not the case that they’re breathless for another reason or that their symptoms are not for something else. There are other things that cause people to have symptoms of heart failure. Anemia, for example, makes people tired and can make people short of breath. The therapies that we use to treat heart failure aren’t necessarily going to help patients with anemia. When we have elevated injection fraction and suspect heart failure, we need some additional assurance that the patient has heart failure. The natriuretic peptides can be useful in those patients to ensure that the signs and symptoms are due to heart failure because that tells us that there is increased wall stress in the heart likely caused by increased filling pressures in the heart.

How do we modify the course of the disease in patients with heart failure? If we’re dealing with heart failure with reduced ejection fraction, we have disease-modifying therapies that have been proven in clinical trials over the last 20 years. These include the renin-angiotensin system inhibitors, ACE inhibitors, and ARBs, although those have been largely replaced, or they should be replaced, with the angiotensin receptor neprilysin inhibitor, sacubitril-valsartan. That would be in addition to beta-blockers, which have been shown to reduce morbidity and mortality in and heart failure. There are also mineralocorticoid receptor antagonists, which have been shown to reduce morbidity and mortality in heart failure. Most recently, SGLT2 inhibitors have been shown to reduce morbidity and mortality in heart failure. We have several classes of drugs that have been proven to be disease modifying.

And when I say disease modifying, it’s not just that they improve morbidity and mortality: They cause structural changes in the heart. As a community, we’ve been able to show that many of these therapies cause reverse left ventricular remodeling; that is, a reduction in the size of the heart and even an improvement in left ventricular function. That’s true of beta-blockers, that’s true of ACE inhibitors, that’s true of sacubitril-valsartan, and that’s true of mineralocorticoid receptor antagonists. The data are coming from SGLT2 inhibitors as well, I suspect.

Jaime Murillo, MD: A great question is this: How do we monitor for patients with heart failure in the health plan? I can tell you that this has been 1 of the biggest challenges that health care in general, not just on the health plan side, has faced over the past 10 to 15 years, and we continue to evolve. I will candidly say that we still have a lot of opportunities.

Some of the current approaches include management programs for chronic conditions directed specifically to heart failure. It is such an important area that we have a program specifically designed for that. We heavily use RPM, which is remote patient monitoring. There are also nurses who have panels of members of the health plan assigned to them to monitor patients on a regular basis. We are experimenting with artificial intelligence–based approaches to create a more dynamic environment. We’re designing a hub that will be able to provide digital access for those patients. We also work with ACOs [accountable care organizations] and other groups that are interested in lowering the total cost of care, so we can design programs where they can have either digital access or brick-and-mortar access. We are also piloting programs where we use voice recognition, utilizing speakers at home where the patient can communicate with a health care provider just utilizing voice. These are just some of the approaches. The fact that I mentioned so many programs shows that we still don’t have a solid, comprehensive A-to-Z approach to the management of heart failure, and I don’t think anybody has this.

What quality metrics do we follow for patients with heart failure? I’ll tell you what exists today and what we should have tomorrow. We’ve had these conversations in the Heart Failure Collaboratory, which is a group of doctors who have a ton of research experience and clinical experience in heart failure. As of today, if you look at it from the health plan standpoint, we still have a fairly narrow approach, which is traditional. As you recall, the FDA requires hard outcomes to assess the value of approaches to heart failure, mainly hospitalization, either cardiovascular hospitalization or all hospitalization. They also track mortality from cardiovascular causes or all causes, and they track readmission to the hospital for cardiovascular or all causes. These are the main metrics that we monitor.

Of course, we also look into what the total cost of care is for someone across a 12-month calendar year. However, we need to incorporate some newer elements. The first is the patient’s quality of life. Second, we should monitor patient-reported outcomes. How do they feel? Do they feel any better? Even though we’re not necessarily prolonging their lives, they have a better quality of life. A majority of patients will accept that. They said, “I don’t care if I don’t live any longer. If I have a better quality of life every day of my life, I’ll take it.” We still don’t provide enough value to that. There is an opportunity for us to value that better. As you can see, many of the trials lately are focusing on quality-of-life questionnaires and so on. That’s an area where we still have an opportunity equally for the patient-reported outcomes.