Biomarkers in Heart Failure
Measure BNP or NT-proBNP in all patients with suspected heart failure presenting with dyspnea—these biomarkers are essential for both ruling out the diagnosis and establishing prognosis. 1
Diagnostic Recommendations
Primary Biomarkers for Diagnosis
Natriuretic peptides (BNP and NT-proBNP) are the gold standard biomarkers for diagnosing heart failure, with Class I, Level A recommendation from ACC/AHA. 1 Both markers provide comparable diagnostic accuracy, so choose based on local laboratory availability rather than clinical superiority. 2, 3
Diagnostic Thresholds for Ruling Out Heart Failure
Use these cut-offs to exclude acute heart failure:
- BNP <100 pg/mL: Effectively rules out heart failure with 95% sensitivity and 94% negative predictive value 1
- NT-proBNP <300 pg/mL: Excludes acute heart failure with 99% sensitivity and 98% negative predictive value 1, 4
- MR-proANP <120 pmol/L: Rules out heart failure with 95-97% sensitivity 1
At these lower thresholds, natriuretic peptides have excellent ability to exclude acute heart failure, making further cardiac workup unnecessary. 1, 3
Diagnostic Thresholds for Confirming Heart Failure
For ruling in heart failure, use higher thresholds:
- BNP ≥100 pg/mL: Supports heart failure diagnosis with 81% diagnostic accuracy in acute dyspnea 2
- NT-proBNP age-adjusted thresholds 4, 3:
- <50 years: ≥450 pg/mL
- 50-75 years: ≥900 pg/mL
75 years: ≥1,800 pg/mL
- NT-proBNP >2,000 pg/mL: Strongly suggestive of heart failure—expedite echocardiography and specialist evaluation within 2 weeks 4, 3
Gray Zone Interpretation
BNP 100-400 pg/mL or NT-proBNP 300-2,000 pg/mL represents a gray zone requiring clinical correlation and confirmatory echocardiography. 3 Specificity is variable at these intermediate levels, so imaging confirmation is mandatory before establishing the diagnosis. 1
Critical Confounding Factors
Obesity
Obesity causes falsely low natriuretic peptide levels, reducing diagnostic sensitivity. 4, 3 Each unit increase in BMI correlates with lower levels, and severe obesity (BMI >35 kg/m²) significantly impairs the ability to detect heart failure. 4, 2 In obese patients with heart failure, BNP may be only 60-100 pg/mL despite symptomatic disease. 3
Renal Dysfunction
Reduced renal clearance elevates both BNP and NT-proBNP levels. 4, 2 Use adjusted thresholds: NT-proBNP 1,200 pg/mL when GFR <60 mL/min/1.73 m². 4 Severe renal failure (GFR <30 mL/min/1.73 m²) makes both detection and exclusion of heart failure less accurate despite adjusted cut-offs. 4
Other Confounders
Additional factors that elevate natriuretic peptides include 4, 2:
- Atrial fibrillation (significantly higher median levels)
- Pulmonary embolism
- Pulmonary hypertension
- Advanced age (always use age-adjusted interpretation)
Prognostic Biomarkers
Natriuretic Peptides for Risk Stratification
Measurement of baseline BNP or NT-proBNP on hospital admission is useful to establish prognosis in acutely decompensated heart failure (Class I, Level A). 1 Higher admission levels are associated with greater risk for all-cause mortality, cardiovascular mortality, and morbidity. 1
In chronic heart failure, BNP or NT-proBNP measurement establishes prognosis and disease severity (Class I, Level A). 1
Specific prognostic thresholds:
- Each 100 pg/mL increase in BNP: ~35% higher relative risk of death 4, 3
- Each 500 pg/mL increase in NT-proBNP: 3.8% increased mortality risk 4, 3
- NT-proBNP >5,000 pg/mL: Indicates very high risk in acute settings 4
Cardiac Troponin
Measurement of cardiac troponin on admission provides independent prognostic value in acute decompensated heart failure (Class I, Level A). 1 Elevated troponin levels are commonly found even without obvious myocardial ischemia or coronary artery disease, and are associated with worse clinical outcomes and higher risk of death. 1
Emerging Biomarkers for Additional Risk Stratification
Consider measuring these biomarkers for additional risk stratification beyond natriuretic peptides 1, 5:
- Soluble suppression of tumorigenicity-2 (sST2)
- Galectin-3
- High-sensitivity troponin
- Mid-regional pro-adrenomedullin (MR-proADM)
- Growth differentiation factor-15 (GDF-15)
However, the clinical role of these emerging biomarkers remains partially defined, and they should not replace natriuretic peptides as first-line diagnostic and prognostic tools. 5, 6
Treatment Monitoring
Serial Natriuretic Peptide Measurements
BNP/NT-proBNP-guided therapy can be useful to achieve optimal dosing of medical therapy in select clinically euvolemic outpatients in structured management programs. 1 Serial measurements track treatment response and disease progression. 4
Only consider changes >50% in natriuretic peptide levels as clinically significant due to high biological variability (30-50%). 4 Measurements should be obtained after adequate diuresis for more accurate prognostic assessment. 4
Rising levels indicate treatment failure or disease progression, while falling levels suggest decreased risk. 4 However, the usefulness of serial BNP/NT-proBNP measurement to reduce hospitalizations or mortality has not been definitively established. 1
Clinical Implementation Algorithm
Step 1: Measure BNP or NT-proBNP in all patients presenting with dyspnea of uncertain etiology or suspected heart failure 1, 4
Step 2: Apply age-adjusted interpretation for NT-proBNP 4, 3
Step 3: Adjust for confounders (obesity, renal function, atrial fibrillation) 4, 3
Step 4: Interpret results:
- Low levels (<100 pg/mL BNP or <300 pg/mL NT-proBNP): Heart failure excluded—no further cardiac workup needed 3
- Intermediate levels (BNP 100-400 or NT-proBNP 300-2,000): Obtain echocardiography for confirmation 3
- High levels (BNP >400 or NT-proBNP >2,000): Heart failure highly likely—expedite echocardiography and specialist evaluation within 2 weeks 4, 3
Step 5: For confirmed heart failure, use admission levels for prognostic stratification 1
Step 6: Consider serial monitoring with changes >50% as clinically significant 4
Common Pitfalls to Avoid
Do not rely solely on natriuretic peptides without clinical context or confirmatory imaging for positive results. 1, 4 Specificity is only moderate (60-76%), requiring echocardiography to confirm the diagnosis and define the specific cardiac abnormality. 4, 2
Do not fail to account for obesity, renal function, and age when interpreting results. 4, 2, 3 These factors significantly affect levels and can lead to false negatives (obesity) or false positives (renal dysfunction, advanced age).
Do not use natriuretic peptides for routine screening in asymptomatic populations without risk factors. 4 Testing is indicated when clinical diagnosis is uncertain, not when heart failure is clinically obvious. 4
Do not expect tight correlations between natriuretic peptide levels and hemodynamic parameters or ejection fraction. 4 These biomarkers cannot distinguish between systolic and diastolic heart failure, though values tend to be lower in diastolic dysfunction. 3