What is ejection fraction, what values are considered normal or abnormal, and how should reduced ejection fraction be managed?

Ejection Fraction: Definition, Normal Values, and Management

Ejection fraction (EF) is the percentage of blood pumped out of the left ventricle with each contraction, and according to the 2022 AHA/ACC/HFSA guidelines, normal LVEF is ≥50%, with reduced EF defined as ≤40% requiring immediate initiation of quadruple guideline-directed medical therapy. 1, 2

What is Ejection Fraction?

Ejection fraction measures the heart's pumping efficiency—specifically, the proportion of blood volume ejected from the left ventricle during systolic contraction. This metric is fundamental for heart failure classification, prognosis determination, and treatment selection.

Normal and Abnormal Values

Guideline-Based Classification

The 2022 AHA/ACC/HFSA guidelines establish three distinct categories 1, 2:

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

Population-Based Normal Values

Recent meta-analysis data from healthy populations provides more granular normal ranges 3:

• Overall pooled mean LVEF: 62.8% (95% CI: 61.0%-64.7%)
• Lower limit of normal: ~52% for men, ~53% for women
• Upper limit of normal: 73.2%
• Sex differences: Women have slightly higher mean LVEF (63.7%) versus men (61.9%)
• Ethnic variations: Asian individuals show 2-3 percentage points higher LVEF than Black or White individuals

Critical clinical point: An LVEF <50% has less than 5% probability of being normal across all demographic groups, making it highly unlikely to represent normal cardiac function 3.

Management of Reduced Ejection Fraction (HFrEF)

Immediate Quadruple Therapy Initiation

For any patient with LVEF ≤40%, immediately initiate all four foundational therapies simultaneously and titrate to target doses within 6-12 weeks 1, 2, 4, 5:

1. SGLT2 Inhibitors (dapagliflozin or empagliflozin)

   • Start immediately regardless of diabetes status
   • Reduces mortality and hospitalizations

2. ACE Inhibitor/ARB or ARNI (sacubitril-valsartan preferred)

   • ARNI superior to ACE inhibitors when tolerated
   • Reduces mortality and hospitalizations

3. Evidence-Based Beta Blockers (carvedilol, metoprolol succinate, or bisoprolol)

   • Reduces mortality and sudden cardiac death

4. Mineralocorticoid Receptor Antagonists (spironolactone or eplerenone)

   • Reduces mortality and hospitalizations

Management of HFmrEF (LVEF 41-49%)

Patients with mildly reduced EF should receive the same quadruple therapy as HFrEF 6. This category represents a dynamic state—patients often transition to either HFrEF or HFpEF over time, making serial EF measurements essential. The pathophysiology and treatment response closely mirror HFrEF, with recent evidence (including FINEARTS-HF trial) confirming benefit from neurohormonal blockade 6.

Secondary Therapies for Persistent Symptoms

Add these agents when symptoms persist despite optimal quadruple therapy 4, 5:

• Ivabradine: If heart rate >70 bpm on maximum beta blocker
• Hydralazine/Isosorbide Dinitrate: Particularly for Black patients or those intolerant to ACE/ARB/ARNI
• Vericiguat: For recent decompensation despite GDMT
• Digoxin: For symptom control in atrial fibrillation or persistent symptoms

Managing Common Adverse Effects

Hypotension: Reduce or eliminate non-essential vasodilators before reducing GDMT; consider timing of medication administration

Hyperkalemia: Optimize diuretics, consider potassium binders (patiromer, sodium zirconium cyclosilicate) before stopping MRA

Worsening kidney function: Accept creatinine increases up to 30% if stable; adjust doses rather than discontinue

Additional Interventions

Iron replacement: Administer IV iron (not oral) in patients with iron deficiency (ferritin <100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation <20%) to improve functional status and quality of life 4

Device therapy:

• ICD for primary prevention if LVEF ≤35% after 3+ months of optimal medical therapy
• CRT-D if LVEF ≤35% with QRS ≥150 ms and LBBB pattern

Critical Pitfall to Avoid

The most common error is sequential rather than simultaneous initiation of quadruple therapy. Start all four medication classes together at low doses and uptitrate rapidly, rather than waiting months between adding each agent. This approach dramatically improves outcomes and reduces the "clinical inertia" that leaves patients undertreated 5.