What is the preferred biomarker, B-type natriuretic peptide (BNP) or N-terminal pro-b-type natriuretic peptide (NT-proBNP), for evaluating heart failure in patients?

BNP vs NT-proBNP for Heart Failure Evaluation

Both BNP and NT-proBNP are clinically equivalent biomarkers with comparable diagnostic and prognostic accuracy—choose whichever assay your local laboratory offers, as the decision should be based on availability rather than clinical superiority. 1, 2

Clinical Equivalence and Selection Criteria

• BNP and NT-proBNP provide similar diagnostic and prognostic information in heart failure patients, with no clinically meaningful superiority of one over the other. 2, 3
• The American Heart Association and American College of Cardiology recommend using either biomarker based on local laboratory availability rather than perceived clinical advantages. 2
• Both markers rank as the most powerful independent predictors of mortality and morbidity in heart failure after adjusting for clinical characteristics. 3

Key Practical Differences

While clinically equivalent, there are technical distinctions worth noting:

• NT-proBNP has a longer half-life and better stability in circulating blood, making it less susceptible to pre-analytical handling errors. 4
• NT-proBNP may be slightly more discerning for detecting milder left ventricular dysfunction (LVEF <50%) compared to BNP. 4
• BNP has a shorter half-life, which theoretically allows for more rapid assessment of acute changes, though this rarely matters clinically. 2
• The absolute values and cutoff thresholds are NOT interchangeable between assays—you must use assay-specific reference ranges. 2

Diagnostic Thresholds

For BNP:

• <100 pg/mL effectively excludes acute heart failure with 90% sensitivity and 94% negative predictive value. 5
• ≥100 pg/mL supports heart failure diagnosis and warrants further evaluation. 2

For NT-proBNP:

• <300-400 pg/mL effectively rules out heart failure with 99% sensitivity and 98% negative predictive value. 2
• Age-adjusted cutoffs improve accuracy: <50 years use 450 pg/mL; 50-75 years use 900 pg/mL; >75 years use 1800 pg/mL. 2
• 400-2000 pg/mL represents a gray zone requiring clinical correlation and echocardiography. 2
• >2000 pg/mL strongly suggests heart failure and mandates expedited echocardiography and specialist evaluation within 2 weeks. 2

Prognostic Value

• Both biomarkers provide powerful prognostic information independent of their diagnostic utility, with higher values predicting worse mortality and morbidity. 2
• NT-proBNP showed subtle superiority over BNP for predicting combined mortality/morbidity endpoints and heart failure hospitalization in the Val-HeFT trial. 3
• Each 100 pg/mL increase in BNP associates with approximately 35% higher relative risk of death. 2
• Predischarge levels of either marker strongly predict risk of death or hospital readmission. 2

Critical Confounding Factors (Apply to Both Markers)

Obesity:

• Each unit increase in BMI correlates with lower natriuretic peptide levels, reducing diagnostic sensitivity. 2
• Severe obesity (BMI >35 kg/m²) can result in falsely reassuring levels despite symptomatic heart failure—obese HFpEF patients may have BNP of only 60-100 pg/mL. 2
• Consider using 50% lower cutoff values in obese patients, though this lacks validation. 2

Renal Dysfunction:

• Reduced renal clearance elevates both BNP and NT-proBNP levels, particularly NT-proBNP. 2
• For CKD stages 3-4, use adjusted thresholds: BNP >200-225 pg/mL or NT-proBNP 1200 pg/mL when GFR <60 mL/min/1.73 m². 2

Atrial Fibrillation:

• Median NT-proBNP levels are significantly higher in patients with atrial fibrillation, complicating interpretation. 2, 6
• In HFpEF patients with AF and NT-proBNP <400 pg/mL, event rates remain low (8.0 per 100 patient-years), but the relationship between NT-proBNP and outcomes differs compared to those without AF. 6

Age:

• NT-proBNP levels increase with age, requiring age-adjusted interpretation for optimal accuracy. 2

Treatment Monitoring

• Both BNP and NT-proBNP decrease with effective heart failure therapy (ACE inhibitors, ARBs, spironolactone). 2
• Only changes >50% should be considered clinically significant due to high biological variability (30-50%). 2
• Measurements should be obtained after adequate diuresis for more accurate prognostic assessment. 2
• BNP/NT-proBNP-guided therapy can optimize medical dosing in select euvolemic outpatients within structured management programs, though targeting specific thresholds has not consistently improved outcomes in clinical trials. 1, 2

Common Pitfalls to Avoid

• Never rely solely on BNP or NT-proBNP without clinical context or confirmatory echocardiography—specificity is only moderate (60-76%). 2
• Do not use these biomarkers when the clinical diagnosis of heart failure is obvious. 2
• Avoid testing during active neprilysin inhibitor therapy (sacubitril/valsartan) due to variable assay responses. 2
• Do not expect tight correlations between natriuretic peptide levels and hemodynamic parameters or ejection fraction. 2
• Remember that normal levels do not completely exclude HFpEF, where values tend to be substantially lower than in HFrEF. 2

Bottom Line Algorithm

1. Order whichever assay (BNP or NT-proBNP) your laboratory offers—they are clinically interchangeable. 2
2. Apply assay-specific thresholds (not interchangeable between tests). 2
3. Adjust interpretation for obesity (lower values), renal dysfunction (higher values), age (higher values), and atrial fibrillation (higher values). 2
4. Use primarily to exclude heart failure when clinical uncertainty exists—negative predictive value is excellent. 2, 5
5. Confirm all positive results with echocardiography. 2
6. For serial monitoring, only consider changes >50% as clinically significant. 2