Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)

Background

• Heart failure with mildly reduced ejection fraction (HFmrEF), sometimes described as borderline heart failure with preserved ejection fraction, is clinical heart failure with a left ventricular ejection fraction (LVEF) between 41% and 49% with combined mild systolic and mild diastolic dysfunction and may account for 7%-25% of all heart failure.
• Unclear whether HFmrEF is distinct clinical entity or transition zone between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
• Types of HFmrEF include:
  • HFmrEF improved - LVEF was previously < 40% (HFrEF) and has increased
  • HFmrEF deteriorated - LVEF was previously > 50% (HFpEF) and has decreased
  • HFmrEF unchanged - LVEF remains stable over time in range 40%-50%
• Clinical characteristics generally fall between those of HFrEF and HFpEF (features are generally more consistent with HFrEF).

• HFmrEF is often treated similarly as HFrEF, but patients often included in studies evaluating treatment for HFpEF instead.
• Give diuretics to patients with congestion and HFmrEF for relief of signs and symptoms (ESC Class I, Level C)
• Consider sodium-glucose cotransporter-2 (SGLT2) inhibitors to reduce heart failure hospitalizations and cardiovascular mortality in patients with HFmrEF (AHA/ACC/HFSA Class 2a, Level B-R).
• Consider the following medications to reduce risk of heart failure hospitalization and cardiovascular mortality in patients with current or previous symptomatic heart failure with HFmrEF (particularly those on lower end of left ventricular ejection fraction [LVEF] range of 41%-49%) (AHA/ACC/HFSA Class 2b, Level B-NR)
  • beta blockers
  • 1 of the following
    • mineralocorticoid receptor antagonists (MRAs)
    • angiotensin receptor-neprilysin (ARNI) inhibitors
    • angiotensin-converting enzyme (ACE) inhibitors
    • angiotensin receptor blockers (ARBs)
• In self-identified Black patients with LVEF ≤ 35% or with LVEF < 45% plus a dilated left ventricle in New York Heart Association (NYHA) class III-IV despite treatment with an ACE inhibitor or ARNI, beta-blocker, and MRA, consider hydralazine and isosorbide dinitrate to reduce the risk of heart failure hospitalization and death (ESC Class IIa, Level B)
  • iron supplementation
    • in symptomatic patients with left ventricular ejection fraction (LVEF) < 45% and iron deficiency (defined as serum ferritin < 100 ng/mL or serum ferritin 100-299 ng/mL with transferrin saturation [TSAT] < 20%), consider intravenous iron supplementation with ferric carboxymaltose to relieve heart failure symptoms, increase exercise capacity, and improve quality of life (ESC Class IIa, Level A)
    • in symptomatic patients recently hospitalized for heart failure and with left ventricular ejection fraction (LVEF) < 50% and iron deficiency (defined as serum ferritin < 100 ng/mL or serum ferritin 100-299 ng/mL with transferrin saturation [TSAT] < 20%), consider intravenous iron supplementation with ferric carboxymaltose to decrease risk of heart failure hospitalization (ESC Class IIa, Level B)
  • medications to avoid
    • do not use nondihydropyridine calcium channel blockers with negative inotropic effects in patients with left ventricular ejection fraction (LVEF) < 50% (AHA/ACC/HFSA Class 3: Harm, Level C-LD)
    • do not use thiazolidinediones in patients with left ventricular ejection fraction (LVEF) < 50% as they increase the risk of heart failure, including hospitalizations (AHA/ACC/HFSA Class 3: Harm, Level B-R).