What type of heart failure (HF) is characterized by an ejection fraction (EF) of 49%?

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)

An ejection fraction of 49% classifies as heart failure with mildly reduced ejection fraction (HFmrEF). 1

Classification by Ejection Fraction

According to the most recent 2022 AHA/ACC/HFSA guidelines, heart failure is categorized into three distinct groups based on left ventricular ejection fraction (LVEF): 1

• HFrEF (Heart Failure with Reduced EF): LVEF ≤40% 1
• HFmrEF (Heart Failure with Mildly Reduced EF): LVEF 41-49% 1
• HFpEF (Heart Failure with Preserved EF): LVEF ≥50% 1

Your patient with an EF of 49% falls precisely at the upper boundary of HFmrEF. 1

Key Diagnostic Considerations

The diagnosis of HFmrEF requires more than just the ejection fraction measurement: 1

• Clinical symptoms and signs of HF must be present (breathlessness, fatigue, ankle swelling, elevated jugular venous pressure, pulmonary crackles, peripheral edema) 1
• Additional objective evidence is recommended to improve diagnostic specificity, including: 1
  • Elevated natriuretic peptides (BNP or NT-proBNP) 1
  • Evidence of increased LV filling pressures at rest or with provocation (exercise, fluid challenge) 1
  • Structural cardiac abnormalities on echocardiography 1

A single EF measurement may not be adequate because HFmrEF patients typically exist on a dynamic trajectory—either improving from HFrEF or deteriorating toward HFrEF. 1 The trajectory of LVEF over time and the underlying cause should be evaluated. 1

Clinical Characteristics

The 2016 ESC guidelines note that patients with HFmrEF most probably have primarily mild systolic dysfunction with features of diastolic dysfunction. 1 This represents a "grey area" between HFrEF and HFpEF that was specifically defined to stimulate research into treatment approaches. 1

Important Clinical Pitfalls

Do not assume this is simply "borderline normal"—HFmrEF carries significant morbidity and mortality similar to other HF phenotypes. 2, 3, 4 These patients require:

• Serial EF measurements to track trajectory 1
• Aggressive evaluation for underlying etiology (ischemic vs non-ischemic, valvular disease, hypertension) 1
• Assessment of comorbidities that differ from HFrEF (more atrial fibrillation, hypertension; less ischemic etiology and COPD) 4

Treatment considerations: While no specific randomized controlled trials exist exclusively for HFmrEF, emerging evidence suggests these patients may benefit from therapies proven effective in HFrEF, including beta-blockers, ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, and SGLT2 inhibitors. 5, 2, 3, 6