Heart Failure Classification by Ejection Fraction
The 2022 ACC/AHA/HFSA guidelines classify heart failure into three primary categories based on left ventricular ejection fraction (LVEF): HFrEF (LVEF ≤40%), HFmrEF (LVEF 41-49%), and HFpEF (LVEF ≥50%). 1
The Three Main Categories
Heart Failure with Reduced Ejection Fraction (HFrEF)
- Defined as LVEF ≤40% 1, 2
- This category encompasses patients who have historically shown survival benefit from guideline-directed medical therapy in randomized controlled trials, most of which enrolled patients with LVEF ≤35% or ≤40% 1
Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)
- Defined as LVEF 41-49% 1, 3, 2
- Previously termed "mid-range EF," the nomenclature was changed to "mildly reduced" because these patients have LVEF lower than normal 1
- These patients typically exist on a dynamic trajectory—either improving from HFrEF or deteriorating toward HFrEF 1, 3
- A single EF measurement at one time point is inadequate for this category; serial measurements over time are essential to understand the trajectory 1, 3
Heart Failure with Preserved Ejection Fraction (HFpEF)
- Defined as LVEF ≥50% 1, 4, 2
- Represents at least 50% of the heart failure population, with increasing prevalence 1
- The threshold has been variably classified as >40%, >45%, or ≥50% in different guidelines, but the 2022 ACC/AHA/HFSA guideline uses ≥50% 1
Additional Category: Heart Failure with Improved Ejection Fraction (HFimpEF)
- Defined as baseline LVEF ≤40% with subsequent improvement to >40% 2, 5, 6
- This emerging category recognizes that LVEF can improve with treatment, creating a distinct phenotype that requires continued guideline-directed therapy despite improvement 7, 5
Critical Diagnostic Requirements Beyond LVEF
For HFmrEF and HFpEF, the diagnosis requires more than just the LVEF number—you must document clinical symptoms/signs of heart failure PLUS objective evidence of cardiac dysfunction 1, 4, 2:
- Elevated natriuretic peptides: BNP >35 pg/mL (ambulatory) or >100 pg/mL (hospitalized), or NT-proBNP >125 pg/mL 4, 2
- OR echocardiographic evidence of elevated filling pressures: E/e' ≥15, left atrial enlargement, increased relative wall thickness, or short mitral deceleration time 4, 2
- OR invasive hemodynamic measurements showing elevated filling pressures 1
Important Clinical Caveats
The HFmrEF Category is Highly Unstable
- Patients with HFmrEF have <25% probability of remaining in that category after 1 year 8
- The within-person standard deviation of LVEF over time is 7.4%, meaning substantial measurement variability exists 8
- This instability creates risk for undertreatment—don't assume a patient's current category is stable 8
LVEF Follows a Normal Distribution
- LVEF is a continuous variable that follows a normal distribution in the heart failure population 8
- The artificial cutpoints at 40% and 50% create categories, but patients near these boundaries may frequently cross between categories with repeat measurements 8
Structural Heart Disease Must Be Present
- Valvular heart disease, wall motion abnormalities, left ventricular hypertrophy, or chamber dilation must be documented 1, 4
- Valve disease is explicitly recognized as a structural cardiac abnormality that can cause heart failure regardless of EF 4
Relationship to ACC/AHA Stages of Heart Failure
The LVEF classification is separate from and complementary to the ACC/AHA staging system (A, B, C, D), which describes disease progression 1:
- Stage A: At risk for HF (hypertension, diabetes, coronary disease) but no structural heart disease or symptoms 1
- Stage B: Structural heart disease (LV hypertrophy, reduced LVEF, valvular disease) but no symptoms 1
- Stage C: Structural heart disease with current or previous symptoms of HF 1
- Stage D: Advanced HF with marked symptoms interfering with daily life and recurrent hospitalizations despite optimal therapy 1
A patient can be Stage C HFrEF, Stage C HFmrEF, or Stage C HFpEF—the stage describes progression, while the EF category describes phenotype 1.