Practical Guidance for Managing HF with Mildly Reduced Ejection Fraction: New HFSA Scientific Statement

HFmrEF accounts for a substantial proportion of heart failure cases across community cohorts and international registries. However, inconsistent definitions and variable treatment approaches have historically limited clarity in care.

“HFmrEF has often been treated as a gray zone, but patients in this group face real risks, including hospitalization and disease progression,” said Jane E. Wilcox MD, MSc, co-lead author of the statement, Bluhm Cardiovascular Institute of Northwestern University, Northwestern Feinberg School of Medicine. “This statement reinforces that HFmrEF warrants the same level of clinical attention and longitudinal management as other heart failure phenotypes.”

The statement highlights that patients with HFmrEF share important characteristics with both heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), including a high burden of comorbidities. Compared with HFpEF, HFmrEF is associated with a higher prevalence of ischemic heart disease and a greater likelihood of progression to lower ejection fraction over time.

Key Clinical Considerations

The statement outlines practical considerations for clinicians based on available observational data, registry analyses, and clinical trial subgroups:

• Recognition: Patients with symptoms of heart failure and EF 41–49% should be actively identified and followed over time
• Classification: Consistent EF definitions and careful interpretation of imaging are essential
• Assessment: Evaluation should extend beyond EF to include ischemic burden, structural abnormalities, and comorbidities
• Management: Clinicians may consider guideline-directed therapies established in HFrEF, while recognizing current evidence limitations
• Follow-up: Periodic reassessment is critical, as EF can change over time

While the statement does not introduce new treatment recommendations, it provides a practical framework to help clinicians apply existing evidence more consistently in a population that has often fallen between traditional heart failure categories.

“By clarifying how to approach HFmrEF, this statement helps close a longstanding gap in heart failure care and highlights important areas for future research,” said Barry A. Borlaug, MD, co-lead author of the statement, Mayo Clinic.

By consolidating current evidence and identifying key knowledge gaps, the HFSA Scientific Statement aims to improve clinical decision-making and advance research for this increasingly recognized patient population.

Reference:

WILCOX J, LUND L, COX Z, Heart Failure With Mildly Reduced Ejection Fraction: A Heart Failure Society of America Scientific Statement, Journal of Cardiac Failure, 2026;DOI: 10.1016/j.cardfail.2026.01.024