Focus on HFpEF: The Challenging “Other” Form of Heart Failure

If you or a loved one has heart failure, you might know that not all cases are the same. For nearly half of patients, the heart’s pumping strength (ejection fraction) stays normal—but the heart still struggles to relax and fill with blood. This condition, called heart failure with preserved ejection fraction (HFpEF), is one of the most complex areas in cardiology today. Even though it affects millions worldwide, managing HFpEF has long been a puzzle for doctors—and new research is finally unlocking answers.

Chunhui He, MD, from Fuwai Hospital (Chinese Academy of Medical Sciences) and Rongchong Huang, MD, from Beijing Friendship Hospital (Capital Medical University), recently reviewed the latest HFpEF evidence in a commentary for the Chinese Medical Journal. Their work highlights why HFpEF is so tricky—and how new guidelines and trials are changing care.

What Is HFpEF, and Why Is It Hard to Treat?

HFpEF occurs when the left ventricle (the heart’s main pumping chamber) can’t relax properly. This stiffness means the heart can’t fill with enough blood, leading to fluid buildup and symptoms like shortness of breath, fatigue, or swelling in the legs. The key difference from heart failure with reduced ejection fraction (HFrEF) is that HFpEF patients have an ejection fraction (EF)—a measure of the heart’s pumping efficiency—of 50% or higher.

The challenge? Symptoms like fatigue or trouble breathing are nearly identical to HFrEF. Doctors can’t tell them apart with a physical exam alone—they need tests like a BNP (brain natriuretic peptide) blood test or an echocardiogram (heart ultrasound) to confirm HFpEF.

Common causes of HFpEF include:

Hypertension: High blood pressure thickens the heart muscle (left ventricular hypertrophy, or LVH), making it stiffer.
Aging: The heart naturally becomes less flexible as we get older.
Comorbidities: Diabetes, atrial fibrillation (an irregular heart rhythm), or valvular heart disease (like aortic stenosis) can worsen HFpEF.
Coronary artery disease (CAD): Even in HFpEF, reduced blood flow to the heart can make relaxation harder.

The Frustration of HFpEF Management—Until Now

For years, only HFrEF patients had proven treatments from large randomized controlled trials (RCTs). As Kai Hu et al. noted in a 2021 review, “Randomized controlled clinical trials did not reveal significant results for HFpEF patients.” But that’s changing.

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines now offer clear steps for HFpEF care:

Class I (Proven to Help): Control blood pressure below 130/80 mmHg; manage fast heart rates in atrial fibrillation with beta-blockers or calcium channel blockers; reduce fluid buildup with a low-salt diet, diuretics (water pills), or nitrates.
Class IIa (Likely Beneficial): If CAD is causing HFpEF, use revascularization (stents or bypass surgery) to restore blood flow. A 10-year follow-up study confirms this improves survival.
Class IIb (May Help): Try angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs, like spironolactone) for symptom relief; consider restoring normal heart rhythm (sinus rhythm) in atrial fibrillation.

New Research Offers Hope for HFpEF Patients

Recent trials are finally giving doctors tools to target HFpEF:

EMPA-REG OUTCOME: This study found that empagliflozin—a drug for type 2 diabetes—cuts HF hospitalizations or cardiovascular death in diabetes patients with heart disease.
TOPCAT: MRAs work better in HFpEF patients with slightly lower EF (around 45–50%), possibly by reducing inflammation and fluid buildup.
PARAGONHF: Sacubatril/valsartan (a combination drug for HFrEF) didn’t help all HFpEF patients—but it did benefit women and those with EF around 57%.

Today, sodium-glucose cotransporter 2 (SGLT2) inhibitors (like empagliflozin) are being tested in HFpEF patients—with or without diabetes. Early results suggest these drugs could become a game-changer.

Living with HFpEF: Improving Quality of Life

HFpEF doesn’t just affect the heart—it disrupts daily life. Many patients struggle with simple tasks like climbing stairs or carrying groceries. But there’s good news:

Exercise Training: Even gentle exercise (like walking or cycling) improves endurance and reduces fatigue.
Caloric Restriction: Losing even a small amount of weight can ease fluid buildup and shortness of breath.

The Future of HFpEF: No Longer “Forgotten”

HFpEF is still complex—but it’s no longer ignored. From better guidelines to cutting-edge trials, doctors are gaining the tools to help patients live better. As more research rolls out, the hope is that HFpEF will move from a “problematic” condition to one with clear, effective treatments.

For anyone living with HFpEF, the message is clear: You’re not alone—and help is on the way.

doi:10.1097/CM9.0000000000001841

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