Fluid Restriction in HF: Let’s Not Torture Patients

This transcript has been edited for clarity. 

Ileana L. Piña, MD, MPH: Hello and welcome. I'm Ileana Piña. I'm professor of medicine at Thomas Jefferson University Hospital and the quality chief for the cardiovascular line, and we are here in Chicago at the American College of Cardiology meeting, which is celebrating its 75th anniversary of exciting work.

I am absolutely thrilled to have as my guest Dr Eileen Hsich. She is director of heart transplant at the Cleveland Clinic, and today we're going to talk about the FRESH-UP trial. 

We don't do studies like this often, where we are determining fluid balance, nutritional balance, electrolytes, sodium, and yet they become very important in a patient's life, because after they leave us, they still have to live in that real world. Eileen, tell us about FRESH-UP.

The FRESH-UP Trial

Eileen M. Hsich, MD: It's a relatively small trial.

Piña: About 200 in each patient group?

Hsich: Yes,comparing fluid restriction — 1500 milliliters a day — to a liberal strategy of drinking what you want, and doing so in a cohort that doesn't have much heart failure symptoms, mostly New York Heart Association Class II, although they did include some Class III. 

Piña: Was this HFrEF (heart failure with reduced ejection fraction)?

Hsich: It was all ejection fractions. The mean was 40%; half of them were HFrEF, but it included mid-range and HFpEF (heart failure with preserved ejection fraction). 

It was a multicenter study that, although small, did try to replicate real-life experiences. 

Piña: How many women were there? 

Hsich: About a third of the patients were female.

Piña: That's not too bad.

Hsich: They really wanted to know about quality of life. That was really the primary endpoint, using the Kansas City questionnaire 

Piña: Did they have anything else to look at thirst, specifically how the patients felt about being thirsty?

Hsich: Not as their primary endpoint. [Editor’s note: The Thirst Distress Scale for Patients With Heart Failure (TDS-HF) at 3 months was a secondary endpoint.]

Piña: So the primary endpoint was purely the KCCQ (Kansas City Cardiomyopathy Questionnaire).

Hsich: And they followed them for 30 days for the primary endpoint — relatively short.

Piña: That should be enough to see differences or something like fluid.

Hsich: They didn't really find many differences. It seemed to be similar, except that there was a slight preference for the liberal strategy. 

Piña: Was it safe? 

Hsich: And it was safe.

Piña: That's a very important point. Because our nursing pool on the floor think that if the patient has too many fluids, then they're going to require more diuretic, and they're going to get puffy and they're going to get swollen.

Hsich: They didn't include hospitalized patients. 

Piña: So these are all outpatients. 

Hsich: Yes, these were outpatients. They were stable. They had been diagnosed at least 6 months ago and they had relatively low NT-proBNP levels.

Piña: What level?

Hsich: The mean was about 400-500 ng/L per arm. They were on really wonderful medical therapy.

Piña: Good background?

Hsich: Almost 80% were on the four pillars (angiotensin receptor-neprilysin inhibitors [ARNI], ,beta-blockers, mineralocorticoid receptor antagonists [MRA], sodium-glucose cotransporter-2 [SGLT2] inhibitor), if not more. We didn't have the doses. 

I liked the fact that they were questioning what we tell our patients, and we tell our patients this routinely, with really little data. What we've learned is that it’s that outpatient who is stable and comes in for a well visit who could tolerate liberalizing their fluids.

Do Patients Need Daily Diuretic?

Piña: I'm trying to take patients off their diuretics because of the jackknife renin angiotensin increase that is not always recognized and certainly not always acted upon. The guidelines do tell us that some patients may not need that daily diuretic if you can get them to weigh themselves. It doesn’t need to be anything fancy, just a scale at home. 

I do the flexible diuretic regimen: If you gain 3 pounds in 3 days (I remind them about baseball — three strikes), you take the diuretic. I think that by avoiding the daily diuretic, patients actually do better, as long as the physical exam remains stable. 

When you're giving the patients instructions, the new patients know nothing, and we spend at least an hour with a new patient: "You need to couple the diuretic regimen with the fluid intake." They ask our pharmacists all the time, "Well, do I drink water with the medicines? Can I take them on an empty stomach?" 

The other thing that we forget is that when patients are really sick with heart failure, especially early on, when they're not on a RAS inhibitor, angiotensin II is a powerful driver of thirst. These patients are so thirsty, and if you're trying to restrict the fluids, I think it's like torturing them. I reach for the RAS inhibition first because I know that will improve their symptoms. Your thoughts?

Hsich: Does everyone need a diuretic? That's an incredibly important question, given the fact that we do it for symptoms, and it actually does trigger the entire RAS, as well as sympathetic, and so it does create its own cycle. And what you're doing is breaking that.

Do you still use the SGLT2 inhibitor if you're telling them that they don't need to use a diuretic? 

Piña: I love my SGLT2 inhibitors. 

Hsich: Because it makes you pee, also.

Piña: It makes you pee. And I tell the patients, "This is trying to protect your kidney." We’ve never really had a drug that we could clearly say that about. It protects the kidney, and it's easy to take once a day — one dose.

Hsich: And it doesn't make you have that urgency. It makes people feel more normal and they don't have to rush to the bathroom. 

Piña: I don’tt ake the SGLT2 inhibitor away at all, but I do try to get them into the habit of weighing themselves daily.

Hsich: I use a totally different strategy. 

Piña: Good — I want to hear it. 

Hsich: It's based on the fact that the first few patients I ever met in real-life clinic were 100 pounds up from fluid.

So, not like the patients from FRESH-UP. I was shocked at the amount of fluid that somebody could have. And, of course, I admitted them.

Piña: It’s surprising how much can get held in the third space and the belly.

Hsich: I asked the patients, "How did you not notice that you were gaining weight?" And they said, "But I didn't change on the scale." When the first person said this, I thought they were lying. I was thinking, How could you not know? After a second patient said the same thing, I started to think about that as a concept and realized that it is very plausible.

When you develop shortness of breath and then proceed to have congestion in your liver, you lose your appetite, so you're not taking in calories.

Piña: That's true.

Hsich: You're gaining water and it's balancing out. And as you continue, you can fit a lot of fluid in that third space, as you said, and your appetite goes down even further if you are developing liver congestion. And with that, your mobility diminishes because you get short of breath.

Piña: They don't move much and they get deconditioned.

Hsich: They're losing muscle mass and they continue to gain water. So is it possible? It actually is. 

When I asked those patients who claimed that they gained 100 pounds but their weight didn't change, "Did you notice that your legs were swelling? Did you notice that you couldn't get your pants on?" They said, "Yeah." 

Piña: For the women, it's the bra. 

Hsich: They all said that they had signs and symptoms, but the weight on the scale didn’t change. Now, I ask them to start doing what you're doing, make an adjustment only if you have these symptoms. I think that provides some control and hopefully reduces hospitalizations.

Piña: My "3 pounds in 3 days" is very short term. What you were talking about is more long term — those people who have gained 100 pounds, are not walking, and are not doing much. And the eating is very important. We have a lot of diabetics and they get that early-satiety syndrome, so they're not eating. And probably when they are eating, it’s not very healthy. 

We need trials that mimic life without having to make it so difficult for the patients. We're talking about food, sodium. I still believe in sodium restriction, 2 grams, but again, making it simple for them: No lunch meats, no salt shaker at the table, and you can cook with a little bit of salt. In essence, a 2-grams-of-sodium diet. Because if you have to choose — you have the fluid, the meds, and the activity — which would you rather have them concentrate on? I want them to take their meds. 

Hsich: Because we know the natural history without medication. It’s still all over the internet, saying that you're going to die within 5 years, which is not based on our current regimen.

Piña: No, not at all.

Hsich: I too feel strongly about medication. I actually favor beta-blockers. I think they really changed our entire approach. 

Piña: Totally. I didn't see reverse remodeling until we started using beta-blockers.

Hsich: Thank you for saying that. It is so important. The RAS inhibition starts to improve the dimension of the heart, the strength of the heart.

Piña: And how our patients feel. 

Hsich: And how the patients feel. It makes a big difference. We even use them with more advanced heart failure. They're the one drug that can help with the reverse remodeling. 

Piña: Some of my colleagues are so focused on getting the SGLT2 inhibitor on board that the MRAs often fall off, and we are not doing the uptitration of beta-blockers that we used to do. I see a lot of people on 50 mg of metoprolol or 3.125 mg of carvedilol — a placebo dose

Hsich: It is on us to specify what is the most important thing to do first. What is going to give us the biggest bang? When you have low blood pressure, what do you need to titrate first, and to also reinforce that if you really have no heart failure symptoms, we don't need to restrict your fluids? We can balance the taking of medications with some quality of life.

Piña: Use some common sense. Eileen, thank you for coming today. I hope the audience has enjoyed this free-flow conversation. We have these great drugs that we did not have before. So do the right thing and use precision medicine — every patient is a little bit different. This isn’t a cookbook.

Hsich: And challenge dogma. You always taught me to question and never to assume that just because we do something, that it's the right thing to do.

Piña: Thank you for joining me today. This is Ileana Piña, signing off. 

Ileana L. Piña, MD, MPH, is a heart failure and cardiac transplantation expert. She serves as an advisor/consultant to the FDA's Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982. Originally from Havana, Cuba, she is passionate about enrolling more women and minorities in clinical trials. She also enjoys cooking and taking spin classes.