What are the B-type natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) thresholds indicative of heart failure?

BNP and NT-proBNP Thresholds for Heart Failure Diagnosis

For heart failure diagnosis, BNP levels >100 pg/mL and NT-proBNP levels >300 pg/mL are the established thresholds for ruling out heart failure, with higher thresholds providing greater specificity for confirming the diagnosis. 1, 2

Diagnostic Thresholds

BNP Thresholds

• Rule-out threshold: ≤100 pg/mL (high sensitivity 95%, NPV 94%) 1
• Intermediate range: 100-400 pg/mL (increased specificity 86%) 1, 2
• Rule-in threshold: >400 pg/mL (high specificity) 2

NT-proBNP Thresholds

• Rule-out threshold: ≤300 pg/mL (excellent sensitivity 99%, NPV 98%) 1
• Intermediate range: 300-1800 pg/mL (improved specificity 76%) 1
• Rule-in threshold: >2000 pg/mL (high specificity) 2

Diagnostic Performance

• BNP at ≤100 pg/mL has sensitivity of 95% and specificity of 63%, making it excellent for ruling out heart failure 1
• NT-proBNP at ≤300 pg/mL has sensitivity of 99% and specificity of 43%, making it slightly superior for ruling out heart failure 1
• As thresholds increase, sensitivity decreases but specificity improves for both markers 1
• There is no statistically significant difference between BNP and NT-proBNP at their respective rule-out thresholds (p>0.05) 1

Age-Adjusted NT-proBNP Thresholds

Some evidence supports age-adjusted NT-proBNP cutpoints 3:

• <50 years: 450 pg/mL
• 50-75 years: 900 pg/mL

• 75 years: 1800 pg/mL

Factors Affecting Interpretation

• Atrial fibrillation: NT-proBNP to BNP ratio is higher (8.03:1) compared to patients without AF (5.75:1) 4
• Age: Both peptides increase with age, with NT-proBNP showing greater increases 4
• Renal function: Levels increase with declining renal function 4
• Body mass index: Affects the NT-proBNP to BNP ratio 4
• Clinical stability: Patients with treated chronic stable heart failure may have levels in the normal range despite having heart failure 5

Clinical Application Algorithm

1. Initial assessment:

   • Use BNP ≤100 pg/mL or NT-proBNP ≤300 pg/mL to rule out heart failure (high negative predictive value)
   • If levels are above these thresholds, proceed to further cardiac evaluation

2. Diagnostic classification:

   • BNP:
     • Normal: <100 pg/mL
     • Raised: 100-400 pg/mL
     • High: >400 pg/mL
   • NT-proBNP:
     • Normal: <400 pg/mL
     • Raised: 400-2000 pg/mL
     • High: >2000 pg/mL 2

3. Monitoring response to therapy:

   • Significant changes in BNP levels are only clinically relevant if they exceed 30-50% from baseline
   • BNP requires a >60% change to be considered clinically significant 2
   • A reduction >30% in follow-up BNP measurement (1-2 months after treatment initiation) indicates good response 2

Pitfalls and Caveats

• False elevations can occur with pulmonary or renal diseases (e.g., chronic hypoxia) 5
• NT-proBNP has better stability in circulating blood and may be more discerning for detecting and evaluating heart failure 6
• The NT-proBNP to BNP ratio is approximately 6.25:1 but varies considerably with clinical factors 4
• Both peptides have similar relationships with age, left ventricular ejection fraction, ventricular diameter, and creatinine clearance 7