Can Pro-BNP Differentiate Between HFpEF and HFrEF?
No, pro-BNP levels cannot reliably differentiate between heart failure with preserved versus reduced ejection fraction—while HFpEF patients typically have lower absolute BNP values than HFrEF patients, there is substantial overlap in ranges, and for any given BNP level, the prognosis is equally poor in both types of heart failure. 1, 2
Why BNP Levels Differ Between HFpEF and HFrEF
Pathophysiologic Basis for Lower BNP in HFpEF
Patients with HFpEF have fundamentally lower myocardial wall stress despite elevated filling pressures because they have small LV cavities and thick LV walls, which produces less stimulus for BNP production compared to the dilated ventricles seen in HFrEF 1
Circulating natriuretic peptide levels are elevated in HFpEF compared to patients without heart failure, but are consistently lower than concentrations seen in HFrEF 1
In HFpEF, BNP levels are directly related to increased LV end-diastolic wall stress, but this stress remains much lower than in HFrEF even when diastolic pressures are similarly elevated 1
Typical BNP Ranges (But With Significant Overlap)
Suggested diagnostic partition values for HFpEF are BNP ≥100 pg/mL and NT-proBNP ≥800 pg/mL, but these thresholds do not distinguish HFpEF from HFrEF 1
Research demonstrates that while median BNP levels differ between groups (HFrEF patients had higher levels at rest: 984 vs 780 pg/mL), the ranges overlap substantially 3
Up to one-third of patients with HFpEF may have normal BNP levels despite significantly elevated filling pressures on invasive assessment 1, 4
Critical Clinical Caveat: Equal Prognostic Value Despite Different Absolute Levels
The Most Important Finding
For any given BNP level across the entire spectrum of ejection fraction, the associated risk of adverse outcomes (mortality and HF hospitalization) is similar in HFpEF patients as in those with reduced ejection fraction 2
A large study of 615 heart failure patients found that while BNP levels were significantly higher in reduced EF patients (p < 0.001), BNP was a strong predictor of outcome but LVEF was not 2
When similar BNP levels are compared across different cutoff levels of LVEF, the prognosis in HFpEF is as poor as in HFrEF 2
Prognostic Application
In the I-Preserve study of 3,480 HFpEF patients, NT-proBNP above the median of 339 pg/mL was independently associated with nearly 80% increase in risk of mortality and cardiovascular hospitalizations 1
The prognostic information provided by NT-proBNP appears similar in both HFpEF and HFrEF, with changes in NT-proBNP over time associated with outcomes in both conditions 1
Confounding Factors That Affect BNP Interpretation
Factors That Lower BNP in HFpEF (Beyond the Pathophysiology)
Obesity significantly reduces BNP levels in HFpEF patients—some obese patients with symptomatic HFpEF have BNP of only 60-100 pg/mL, which rises to >100 pg/mL after weight loss from bariatric surgery 1, 4
Chronically treated heart failure patients, especially those younger than 75 years, may have normal-range BNP levels despite active disease 4
Enhanced clearance and degradation of natriuretic peptides in HFpEF contributes to lower measured levels 4
Factors That Raise BNP Independent of Heart Failure Type
Atrial fibrillation, renal dysfunction, older age, female sex, pulmonary disease (COPD, pulmonary hypertension, pulmonary embolism), and sepsis all elevate BNP levels independent of LV dysfunction 1
These comorbidities may require adjustment of partition values, but no validated algorithms exist for distinguishing HFpEF from HFrEF in their presence 1
African American patients exhibit lower NT-proBNP levels, potentially linked to salt-sensitive hypertension and left ventricular hypertrophy 4
The Correct Clinical Approach
What You Actually Need to Differentiate HFpEF from HFrEF
Echocardiography with ejection fraction measurement is the definitive method to distinguish preserved from reduced ejection fraction heart failure—BNP helps confirm the diagnosis of heart failure itself but cannot replace imaging for EF determination 5, 6
Diagnostic Algorithm
Use BNP/NT-proBNP to support the diagnosis of heart failure when clinical uncertainty exists (Class I recommendation) 1
Obtain echocardiography to measure ejection fraction: HFrEF is defined as EF ≤40%, HFpEF as EF ≥50% 1, 6
Before confirming HFpEF, systematically exclude other causes of elevated natriuretic peptides with normal EF: atrial fibrillation, acute coronary syndrome, valvular disease, pulmonary embolism, COPD with cor pulmonale, pulmonary hypertension, and renal failure 5
For HFpEF diagnosis, require all of the following: HF symptoms/signs, preserved EF, elevated natriuretic peptides, and objective evidence of cardiac structural/functional abnormalities 5
Common Pitfall to Avoid
Do not assume that a lower BNP level means HFpEF rather than HFrEF—the only way to know is direct measurement of ejection fraction 1, 2
Do not over-rely on BNP in patients with HFpEF, as levels may be misleadingly low due to obesity, chronic treatment, or reduced wall stress 4
In patients with unexplained dyspnea and borderline BNP, consider exercise testing or stress echocardiography to reveal elevated filling pressures not apparent at rest 6