News|Articles|May 20, 2026

HFSA Calls for Reclassification of HFmrEF as a Distinct Heart Failure Phenotype

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Key Takeaways

Reclassifying HFmrEF as a stable phenotype aims to reduce therapeutic inertia and GDMT underuse driven by heterogeneous labeling and clinician uncertainty.
Pathobiologic overlap with HFrEF supports applying HFrEF-directed pharmacotherapies more systematically in LVEF 41%–49% populations.
Standardized LVEF imaging/reporting and structured EHR phenotype fields are positioned as prerequisites for consistent diagnosis, trial enrollment, and quality measurement.
Incorporation of HFmrEF into performance benchmarks could improve risk stratification and resource allocation while requiring coordination across coding, formularies, and quality programs.
Dedicated randomized trials in HFmrEF are prioritized to replace reliance on subgroup extrapolations and refine phenotype-specific treatment effects.

New scientific statement argues that heart failure with mildly reduced ejection fraction should no longer be treated as a “gray zone.”

A new scientific statement from the Heart Failure Society of America (HFSA) is challenging long-standing clinical conventions by recommending that heart failure (HF) with mildly reduced ejection fraction (HFmrEF) be recognized as a distinct and actionable phenotype rather than a transitional category between preserved and reduced ejection fraction.¹

“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 co-lead author of the statement, Barry A. Borlaug, MD, Mayo Clinic.

Published in the Journal of Cardiac Failure, the statement synthesizes emerging evidence suggesting that patients with left ventricular ejection fraction (LVEF) between 41% and 49% demonstrate unique clinical characteristics, treatment responses, and outcomes that warrant more precise categorization and management.

Moving Beyond the In-Between Label

Historically, HFmrEF has been treated as a heterogeneous group—often described as a “gray zone” between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). However, HFSA authors argue this framing has contributed to inconsistent treatment patterns, underuse of guideline-directed medical therapy, and uncertainty in clinical decision-making.

Instead, the statement emphasizes that HFmrEF shares overlapping pathophysiologic mechanisms with HFrEF, including neurohormonal activation and myocardial remodeling, suggesting that many patients may benefit from similar therapeutic strategies.

The authors call for HFmrEF to be operationalized as a discrete phenotype with standardized diagnostic criteria, particularly in electronic health records, clinical trials, and quality measurement frameworks.

Treatment Implications

Beyond clinical treatment, the HFSA statement frames the HFmrEF classification as a systems-level issue. Variability in how ejection fraction is measured and reported across institutions leads to disparities in diagnosis and treatment initiation.

The statement recommends:

Standardized imaging and reporting protocols for LVEF
Clear documentation of HF phenotypes in structured EHR fields
Integration of HFmrEF into quality metrics and performance benchmarks

These recommendations are intended to reduce variation in care delivery and improve adherence to evidence-based therapies.

Guideline Convergence

The push to refine HF phenotypes aligns with prior recommendations from the joint 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure, which already acknowledged HFmrEF as a distinct category and suggested potential benefit from HFrEF-directed therapies.²

However, the new HFSA statement goes further, explicitly arguing that HFmrEF should not remain a transitional classification and instead should be treated as a stable diagnostic entity in both clinical practice and research design.¹

Similarly, the European Society of Cardiology heart failure guidelines have increasingly emphasized phenotype-based treatment approaches, reflecting a broader international shift toward more granular HF classification systems.³

Implications for Managed Care and Future Research

For payers and health systems, clearer HFmrEF definitions could improve risk stratification, optimize therapy allocation, and reduce avoidable hospitalizations. However, implementation will require alignment across coding systems, quality measures, and formulary policies.

The statement also identifies persistent evidence gaps, particularly the need for dedicated randomized trials focused exclusively on HFmrEF populations rather than extrapolated subgroup analyses.

As HF classification continues to evolve, HFmrEF may no longer sit between 2 established categories but instead emerge as a central phenotype in its own right, reshaping how clinicians, researchers, and payers approach disease management.

References

1. New HFSA Scientific Statement provides practical guidance for managing heart failure with mildly reduced ejection fraction. HFSA. News release. April 22, 2026. Accessed May 20, 2026. https://hfsa.org/new-hfsa-scientific-statement-provides-practical-guidance-managing-heart-failure-mildly-reduced

2. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Card Fail. 2022 May;28(5):e1-e167. doi:10.1016/j.cardfail.2022.02.010

3. McDonagh TA, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023 Oct 1;44(37):3627-3639. doi:10.1093/eurheartj/ehad195