Cardiology AdvisorHFSA Releases Scientific Statement on Heart Failure With Mildly Reduced EF

✅ Guideline Update

The HFSA scientific statement, published in the Journal of Cardiac Failure, defines HFmrEF as EF 41%–49% with HF symptoms and objective evidence of congestion, characterizes the population as phenotypically intermediate between HFrEF and HFpEF, and recommends quadruple therapy consistent with HFrEF management on the basis of current evidence.

Clinical Considerations

• HFmrEF patients are typically aged 65–80, with higher prevalence of ischemic heart disease, atrial fibrillation, and diabetes; male sex independently predicts a 63% increased risk
• No dedicated interventional trials exist; evidence is derived from post-hoc analyses of HFpEF and broad-spectrum HF trials
• SGLT2 inhibitors (empagliflozin, dapagliflozin) demonstrate consistent benefit across the full EF spectrum, including HFmrEF, with or without type 2 diabetes
• Neurohormonal antagonists (ARNis, beta-blockers, ACEi/ARBs, MRAs) appear effective in HFmrEF but not HFpEF in early trials; semaglutide showed symptom and functional benefit in patients with obesity and EF ≥45%

Practice Applications

• Consider quadruple therapy for HFmrEF patients consistent with HFrEF protocols, per HFSA guidance
• Recognize HFmrEF as a heterogeneous phenotype; some patients may trend toward HFrEF, others toward HFpEF
• Monitor for congestion using echo Doppler, natriuretic peptides, or invasive hemodynamics when noninvasive findings are inconclusive
• Integrate ischemia evaluation into HFmrEF workup, given the significant causal role of coronary disease