What is ejection fraction (EF), what are its normal values, and how should reduced EF be managed in heart failure?

Ejection Fraction: Definition, Normal Values, and Management of Reduced EF

What is Ejection Fraction?

Ejection fraction (EF) is the stroke volume divided by the end-diastolic volume of the left ventricle, representing the percentage of blood ejected from the ventricle with each contraction 1.

• EF is primarily determined by the end-diastolic volume of the ventricular chamber—a dilated heart typically has a reduced EF 1.
• EF is crucial for classifying heart failure patients because it determines prognosis, response to therapies, and guides clinical trial enrollment 1.
• Most patients with heart failure have evidence of both systolic and diastolic dysfunction regardless of EF 1.

Normal Values and Classification

The 2022 AHA/ACC/HFSA guidelines define three EF categories: HFrEF (≤40%), HFmrEF (41-49%), and HFpEF (≥50%) 1, 2.

Specific Thresholds:

• HFrEF (Heart Failure with Reduced EF): LVEF ≤40% 1, 3
• HFmrEF (Heart Failure with Mildly Reduced EF): LVEF 41-49% 1, 2, 3
• HFpEF (Heart Failure with Preserved EF): LVEF ≥50% 1, 3

Important clarification: An EF between 45-50% falls within the HFmrEF range (41-49%), NOT HFpEF—only values ≥50% meet criteria for preserved EF 2.

Diagnostic Requirements Beyond EF:

For HFmrEF and HFpEF, the diagnosis requires more than just symptoms and EF measurement 1, 2:

• Elevated natriuretic peptides: BNP >35 pg/mL or NT-proBNP >125 pg/mL 2
• Echocardiographic evidence: Elevated filling pressures (E/e′ ≥15) or diastolic dysfunction 2
• Structural heart disease: Increased left atrial volume index or left ventricular mass index 2

Management of Reduced Ejection Fraction (HFrEF)

Guideline-Directed Medical Therapy (GDMT)

All patients with HFrEF (LVEF ≤40%) should receive comprehensive neurohormonal blockade with ACE inhibitors (or ARBs), beta-blockers, and mineralocorticoid receptor antagonists, as these therapies have proven mortality benefit 1.

The evidence base for HFrEF treatment is robust 1:

• ACE inhibitors reduce mortality by approximately 20-30% 1
• Beta-blockers reduce mortality and hospitalization 1
• Mineralocorticoid receptor antagonists provide additional mortality benefit 1
• These therapies work by reversing left ventricular dilation 4

Device-Based Therapies

For patients with LVEF ≤35% despite ≥3 months of optimal medical therapy, implantable cardioverter-defibrillators (ICDs) are recommended for primary prevention 3.

Specific ICD thresholds 3:

• LVEF ≤35%: ICD recommended for NYHA class II-III patients
• LVEF ≤30%: ICD recommended even for NYHA class I patients
• Avoid ICD within 40 days post-MI due to lack of early benefit 3
• Wearable cardioverter-defibrillator may bridge the 40-day post-MI waiting period for patients with LVEF ≤35% 3

Cardiac resynchronization therapy (CRT) should be considered for appropriate candidates with HFrEF, as it reverses LV dilation and improves outcomes 4.

Management of Improved EF (HFimpEF)

When a patient's EF improves from <40% to 41-50%, continue all HFrEF-directed therapy to prevent relapse—this is classified as heart failure with improved EF (HFimpEF), not HFmrEF 2.

• Patients with improved EF remain at risk for re-deterioration of systolic function 5
• Discontinuation of GDMT frequently leads to recurrence of HFrEF 5
• Serial EF measurements are essential because HFmrEF represents a dynamic trajectory—patients may be improving from HFrEF or deteriorating toward it 1, 2

Management of HFmrEF

Patients with HFmrEF (LVEF 41-49%) should be treated similarly to HFrEF patients, as post-hoc analyses suggest neurohormonal blockade may provide benefit in this population 6.

• HFmrEF shares more clinical features with HFrEF than HFpEF, particularly the high prevalence of ischemic heart disease 6
• Evidence from subgroup analyses and SGLT inhibitor trials suggests drugs effective in HFrEF may also benefit HFmrEF patients 6
• Cardiovascular event risk is lower in HFmrEF than HFrEF but higher than general population 6

Management of HFpEF

No therapies have consistently demonstrated mortality benefit in HFpEF (LVEF ≥50%), so management focuses on aggressive control of comorbidities, particularly systolic hypertension, and avoidance of fluid overload 1, 7.

• Control of systolic hypertension is critical, as hypertension is present in 75% of HFpEF cases 1, 7
• Diuretics prevent fluid overload and flash pulmonary edema, which is characteristic of HFpEF 7
• HFpEF patients are typically elderly women with systolic hypertension 7

Common Pitfalls

• Do not use a single EF measurement to classify HFmrEF patients—serial assessments are required to determine trajectory and underlying cause 1, 2
• Do not discontinue GDMT when EF improves—patients with HFimpEF need continued therapy 2, 5
• Do not assume normal natriuretic peptides exclude HFmrEF or HFpEF—they are supportive but not required for diagnosis 1
• Do not implant ICD within 40 days of MI—use wearable cardioverter-defibrillator as bridge therapy if needed 3