The Heart Failure Society of America (HFSA) has released a new scientific statement encouraging the acceptance of heart failure with mildly reduced ejection fraction (HFmrEF) as its own distinct condition.1
Prior to the statement’s release, HFmrEF has largely been considered a gray zone in between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), and as a result has been understudied. Initially identified by the European Society of Cardiology (ESC) in 2016 and termed heart failure with mid-range ejection fraction, clinical trials have historically overlooked this patient population, leading to limited available evidence.1,2
“There’s been a little confusion out there, especially in people who are outside of heart failure circles, as to who these patients are, whether they justify their own distinction, what we look for, how we treat them, et cetera,” Barry Borlaug, MD, associate professor of medicine at Mayo Clinic and co-author of the statement, told HCPLive in an exclusive interview. “That was really the basis for putting together this expert scientific statement.”
Borlaug and colleagues highlight shortcomings with current HF management and diagnosis, noting that although EF is typically used as a benchmark to differentiate between the major categories, it is an intrinsically imperfect measurement. EF is dependent on a variety of factors, including chamber size, which naturally decreases as chamber volume increases, as well as hemodynamic loading conditions.1
Given these limitations in standard disease identification, Borlaug and colleagues created a series of practical considerations for other clinicians, highlighting 5 major points in HFmrEF diagnosis, treatment, and management. These points include the following:
- Recognition: Patients with symptoms of HF and EF 41-49% should be identified and followed
- Classification: Careful imaging interpretation and consistent EF definitions are needed
- Assessment: Evaluation should include structural abnormalities, ischemic burden, and comorbidities
- Management: Utilize HFrEF guideline-directed therapies while acknowledging current evidence limitations
- Follow-up: Periodic reassessment to account for gradual EF change2
Borlaug and colleagues also created a slide deck containing the top 10 take-home messages from the document, which were drafted as a quick reference guide.
Current evidence, according to the team, indicates that HFmrEF is a heterogeneous group, including patients with clinical features indicating HFrEF and others more closely aligned with HFpEF. The most effective treatment options based on existing data are SGLT2 inhibitors, with MRAs, ARBs, beta-blockers, and combined ARB/neprilysin inhibitors showing evidence from subgroup analyses. Borlaug and colleagues determined that treatment with guideline-directed medical therapy for HFrEF is the most reasonable course of action.1
“The guidelines haven’t given class 1 indications because there haven’t been specific trials, but I think all of us really feel like these people should be treated just like HFrEF,” Borlaug said. “I think that would be the main takeaway – recognize that it is true, legitimate heart failure, and for the most part, treat these patients as though they have HFrEF, with the pillars that we use in that form of heart failure.”
Editors’ Note: Borlaug reports disclosures with AstraZeneca, Cytokinetics, Merck, Novo Nordisk, Tectronic Therapeutics, BridgeBio Pharmacy, and others.
References
WILCOX JE, LUND LH, COX ZL, et al. Heart failure with mildly reduced ejection fraction: A Heart Failure Society of America scientific statement. Journal of Cardiac Failure. Published online April 22, 2026. doi:10.1016/j.cardfail.2026.01.024
