What is the clinical significance of an elevated NT-proBNP (N-terminal pro b-type natriuretic peptide) level in heart failure diagnosis?

From the Guidelines

The NT-proBNP level of 400 pg/mL suggests possible heart failure that requires further evaluation, as it exceeds the age-independent exclusion threshold of 300 pg/mL, and thus, heart failure cannot be ruled out 1. This value falls below the diagnostic cut-points for confirming heart failure across all age groups (450 pg/mL for patients under 50,900 pg/mL for those 50-75, and 1800 pg/mL for those over 75), placing the result in a diagnostic "gray zone" where clinical correlation is essential. Some key points to consider in the interpretation of NT-proBNP levels include:

• The patient's age, as NT-proBNP levels increase with age
• Renal function, as impaired renal function can elevate NT-proBNP levels
• Clinical presentation, as symptoms such as dyspnea, edema, and fatigue can influence the interpretation of NT-proBNP levels Additional cardiac evaluation, including:
• Echocardiography to assess cardiac structure and function
• Clinical assessment of symptoms, such as dyspnea, edema, and fatigue
• Consideration of other cardiac biomarkers, such as B-type natriuretic peptide (BNP) or cardiac troponin would be appropriate to further evaluate the patient's condition, as suggested by the guidelines 1. It is also important to note that NT-proBNP levels reflect cardiac wall stress and ventricular stretch, rising when the heart is under strain, and that the interpretation of this value should consider the patient's overall clinical context, as highlighted in the study by 1.

From the Research

NT-proBNP Cut-Points for Heart Failure Diagnosis

• The suggested cut-points for the use of proBNP for the diagnostic evaluation of heart failure (HF) in patients with acute dyspnea are:
  • Diagnosis (rule in HF):
    • <50 years: 450 pg/mL 2, 3
    • 50-75 years: 900 pg/mL 2, 3

    • 75 years: 1800 pg/mL 2, 3

  • Exclusion (rule out HF): age independent, 300 pg/mL 2, 3

Studies on NT-proBNP Cut-Points

• A study published in 2019 found that event rates in HF with preserved ejection fraction patients without AF and with NT-proBNP <400 pg/mL are low 2
• A study published in 2012 found that the best cut-off point for NT-proBNP to rule out heart failure was 280 pg/mL in a community population attended in primary care 3
• A study published in 2025 found that current recommended rule-out NT-proBNP threshold <125 pg/mL had 82% sensitivity, and a lower rule-out NT-proBNP threshold <50 pg/mL displayed good sensitivity 4
• A study published in 2018 found that low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction 5
• A systematic review published in 2014 found that BNP and NT-proBNP levels are increased in persons with heart failure, and low levels of these peptides rule out HF 6

NT-proBNP Levels and Heart Failure

• NT-proBNP levels can be used to diagnose and exclude heart failure, but the cut-points may vary depending on age, BMI, and other factors 2, 3, 4, 5, 6
• The relationship between NT-proBNP levels and outcomes differs in patients with and without atrial fibrillation 2
• NT-proBNP measurement can improve work-out diagnoses and could be cost-effective in primary care 3