HFmrEF: The Most Common Form of Heart Failure You've Never Heard Of

 Prevalence of HFmrEF

~25%of HF patients have mildly reduced EF

41–49%ejection fraction range defining HFmrEF

±7%error range of standard EF measurement

For too long, heart failure with mildly reduced ejection fraction has occupied an uncertain middle ground — neither squarely HFrEF nor HFpEF, and too often left undertreated as a result. A new scientific statement from the Heart Failure Society of America (HFSA), published in the Journal of Cardiac Failure in April 2026, sets out to change that.

"This is the most common form of heart failure that people have never heard of."

— Jane E. Wilcox, MD, Northwestern University

HFmrEF — defined by an ejection fraction between 41% and 49% — accounts for as many as one in four heart failure cases, depending on measurement thresholds. Despite its prevalence, dedicated clinical trials are conspicuously absent, a gap the statement's authors argue may have been inadvertently discouraging treatment.

Closer to HFrEF than HFpEF

Phenotypically, HFmrEF tends to resemble HFrEF more than its preserved-EF counterpart. Patients commonly present with ischemic heart disease, atrial fibrillation, and diabetes — a profile cardiologists recognize from the HFrEF population. The emerging consensus is that therapies proven in HFrEF likely extend benefit across the mildly reduced spectrum as well.

SGLT2 inhibitors are highlighted as appropriate across the entire ejection fraction spectrum. Beta-blockers, by contrast, carry robust evidence in HFrEF, supportive evidence in HFmrEF, and no meaningful evidence in HFpEF — making this the clearest pharmacologic distinction between groups. Mineralocorticoid receptor antagonists (MRAs) appear applicable broadly.

A phenotype-specific approach

Because ejection fraction is a dynamic and imperfect measure — with a recognized error range of approximately 7% — the HFSA statement encourages clinicians to look beyond the number itself. Comorbidity burden, chamber geometry, and clinical history can help stratify whether a patient with an EF of, say, 46% is better served by an HFrEF or HFpEF management strategy.

More HFrEF-like

Male, coronary disease, dilated chamber, family history of cardiomyopathy — consider ARNI, ACE inhibitor, ARB, beta-blocker

More HFpEF-like

Older female, obesity, atrial fibrillation, non-dilated ventricle — consider GLP-1 based strategy, treat underlying drivers

Looking ahead, as gene therapies and precision medicine reshape cardiology, ejection fraction alone may yield to more granular cardiomyopathy classification as the basis for trial enrollment and treatment decisions. In the meantime, the simplest clinical message may also be the most powerful: HFmrEF is real, it is common, and it deserves treatment.

References

1. Wilcox JE, Lund LH, Cox ZL, et al. Heart failure with mildly reduced ejection fraction: an HFSA scientific statement. J Card Fail. 2026; Epub ahead of print.
2. Maxwell YL. HFmrEF patients take spotlight in new HFSA statement. TCTMD. April 22, 2026.
3. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726.
4. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413–1424.