Episode 212: Managing HFpEF

Hyo Mun and Jordan Redden (medical students) explain how to manage HFpEF with medications and touch some basics about nonpharmacologic treatments. Dr. Arreaza asks insightful questions to guide the discussion. 

Written by Hyo Mun, MSIV, American University of the Caribbean; and Jordan Redden, MSIV, Ross University School of Medicine. Comments by Hector Arreaza, MD.

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Treatment of HFpEF

Arreaza: Mike, if you had to name the one therapy everyone with HFpEF should be on, what is it?

Mike: That's easy! SGLT-2 inhibitors. This is the one slam-dunk we have in HFpEF. Empagliflozin (Jardiance) or dapagliflozin (Farxiga) should be started in essentially every patient with HFpEF, and it doesn't matter if they have diabetes or not.

Jordan: And that’s worth repeating, because people still think of these as “diabetes drugs.” They’re not anymore. In HFpEF, SGLT-2 inhibitors reduce heart-failure hospitalizations, improve symptoms, improve quality of life, and even reduce cardiovascular death.

Dr. Arreaza: They’re also simple. Empagliflozin 10 mg daily or dapagliflozin 10 mg daily. No titration, no drama. The effectiveness of these meds was established around 2019 with DAPA-HF and later with DELIVER. These were trials thatdemonstrated that dapagliflozin reduces worsening heart failure and cardiovascular events across the full spectrum of heart failure, from reduced to preserved ejection fraction, independent of diabetes status.

Mike: And the number needed to treat is about 28 to prevent one heart-failure hospitalization. That’s excellent for a disease where we historically had almost nothing that worked.

Jordan: They’re also safe in chronic kidney disease down to an eGFR of about 25, which makes them even more useful in this population.

Dr. Arreaza: Alright. We got SGLT-2 inhibitor, what’s next?

Mike: Volume management. Loop diuretics are still the backbone of symptom control in HFpEF. If the patient is volume overloaded, you diurese, and you diurese aggressively.

Jordan: The goal is euvolemia. Dry weight, no edema, no orthopnea, no waking up gasping for air. A lot of these patients end up needing chronic oral loop diuretics to stay there.

Dr. Arreaza: Something to remember: HFpEF patients don’t tolerate congestion well, and being “a little wet” is not benign. Let’s move into RAAS inhibition. Where do ARBs and ACE inhibitors fit in?

Mike: Between ARBs and ACE inhibitors, ARBs are the winners in HFpEF. They actually reduce heart failure hospitalizations—drugs like candesartan, losartan, valsartan. ACE inhibitors? Not so much. They showed minimal benefit in older HFpEF patients, which is why we go with ARBs instead.

Jordan: But a lot of clinicians get nervous about ACE inhibitors and ARBs because of kidney function, so it’s worth talking through how these drugs actually work in the kidney.

Dr. Arreaza: Yes, misunderstanding may lead to unnecessary drug discontinuation.

Jordan: Under normal conditions, the afferent arteriole brings blood into the glomerulus, and the efferent arteriole is constricted by angiotensin II. That constriction keeps pressure high in the glomerulus and maintains filtration.

Mike: Here's what happens with an ACE inhibitor: you block angiotensin II, the efferent arteriole relaxes, glomerular pressure drops, and GFR dips slightly. Creatinine bumps up a little, and that scares people, but that's actually the whole point—that's how you get kidney protection long-term.

Jordan: High intraglomerular pressure causes hyperfiltration injury and scarring over time. Lowering that pressure protects the kidney long-term. The short-term GFR drop is the price you pay for long-term benefits.

Dr. Arreaza: So let’s talk about CKD, because this is where people panic.

Mike: Right. ACE inhibitors and ARBs are not contraindicated in chronic kidney disease. In fact, they’re recommended even in advanced stages. They reduce progression to kidney failure by about a third.

Jordan: The key is how you use them. Start low. Check creatinine and potassium one to two weeks after starting, then periodically. A creatinine rise up to 30% from baseline is acceptable. That’s not kidney injury, that’s physiology.

Dr. Arreaza: And what about potassium creeping up?

Mike: You adjust the dose or add a potassium binder. You don’t just automatically stop the drug.

Dr. Arreaza: Now there is one absolute contraindication everyone needs to know about! (board exam test)

Jordan: Bilateral renal artery stenosis. This is the big one. In these patients, the kidneys are completely dependent on angiotensin II–mediated efferent constriction to maintain GFR. Take that away, and GFR collapses.

Mike: Creatinine can jump dramatically within days. If you see a creatinine rise of 20% or more shortly after starting an ACE inhibitor, you should be thinking about bilateral renal artery stenosis and stopping the drug immediately.

Dr. Arreaza: After revascularization, though, many patients can tolerate ACE inhibitors again, so this isn’t always permanent. What about cardiorenal syndrome? That’s where things get uncomfortable.

Mike: It is uncomfortable, but cardiorenal syndrome isn't a contraindication. These patients have severe heart failure and kidney disease, and their mortality is actually higher than patients with heart failure alone.

Jordan: ACE inhibitors still reduce mortality and slow kidney disease progression in this group. Studies show that stopping ACE inhibitors during acute heart-failure admissions increases in-hospital mortality three- to four-fold.

Dr. Arreaza: So we are cautious, but we don’t avoid it.

Mike: Exactly. Start low, titrate slowly, monitor labs closely, accept up to a 30% creatinine rise. You only stop if kidney function keeps worsening, or potassium gets dangerously high.

Dr. Arreaza: Alright. Let’s move on. What about mineralocorticoid receptor antagonists… MRA?

Jordan: Spironolactone or eplerenone might reduce hospitalizations in HFpEF, but the data is mixed. This is more of a “select patients” situation.

Mike: And you have to watch potassium and kidney function carefully, especially if they’re already on an ACE inhibitor or ARB.

Dr. Arreaza: What about sacubitril-valsartan, also known as Entresto®?

Mike: Entresto may help patients with mildly reduced EF roughly in the 45 to 57% range. It’s not first-line for HFpEF, but in select patients, it's reasonable.

Dr. Arreaza: Now let’s clarify one of the biggest sources of confusion: beta blockers.

Jordan: Beta blockers are not a treatment for HFpEF itself. They’re only indicated if the patient has another reason to be on them, like coronary disease or atrial fibrillation.

Mike: And timing really matters here. You absolutely do not start beta blockers during acute decompensated heart failure. Their negative inotropic effects can make things worse when patients are volume overloaded.

Jordan: But, and this is critical, you also don’t stop them if the patient is already taking one. Abrupt withdrawal causes a sympathetic surge and dramatically increases mortality.

Dr. Arreaza: If a patient is admitted on a beta blocker, what do we do?

Mike: Continue it at the same dose or reduce it slightly if they’re really unstable. Once they’re euvolemic and stable, you can carefully titrate up.

Jordan: And watch for chronotropic incompetence. HFpEF patients often rely on heart-rate response to exercise, and beta blockers can worsen exercise intolerance.

Dr. Arreaza: Beyond medications, HFpEF is really about treating comorbidities. Aerobic activity can be an initial strategy to improve exercise intolerance and has evidence of improving aerobic function and quality of life. Sodium restriction: improves symptoms, does not decrease risk of death or hospitalizations.

Mike: Hypertension control is huge. For diabetes, the SGLT-2 inhibitors will perform double duty. For obesity, weight loss improves symptoms, and GLP-1 agonists like semaglutide are absolute gamechangers.

Jordan: Don’t forget sleep apnea, atrial fibrillation, and lifestyle. Exercise improves the quality of life, even if it doesn’t change hard outcomes. Lifestyle is the main treatment. 

Dr. Arreaza: And when should you refer to cardiology?

Mike: You should refer when the diagnosis isn't clear; symptoms are not responding to treatment, difficult volume management, end-organ dysfunction, or if you are concerned about advanced heart failure.

Dr. Arreaza: So, it has been a great discussion. What is the takeaway?

Mike: HFpEF treatment isn't about one magic drug -- it's about volume control, SGLT2 inhibitors, smart use of RAAS blockade, and aggressive management of comorbidities.

Jordan: And it's understanding the physiology, so you don’t withhold life-saving therapies out of fear.

Dr. Arreaza: Well said. If you found this helpful, share it with a friend or colleague and rate us wherever you listen. This is Dr. Arreaza, signing off.

Jordan/Mike: Thanks! 

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