When should N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) or B‑type natriuretic peptide (BNP) be measured, and how should a patient with an elevated result be managed?

Management of Elevated NT-proBNP and BNP Levels

When to Measure Natriuretic Peptides

Measure BNP or NT-proBNP in ambulatory patients with dyspnea when the diagnosis of heart failure is uncertain, as this testing supports clinical decision-making and has high negative predictive value for ruling out heart failure. 1

• In acute care settings, measure BNP or NT-proBNP to support clinical judgment for diagnosing acutely decompensated heart failure 1
• For risk stratification in suspected acute coronary syndrome, BNP or NT-proBNP may be considered as an adjunct (Class IIb recommendation) 1
• Do not routinely measure natriuretic peptides in patients with prior myocardial infarction who should proceed directly to echocardiography 2

Diagnostic Thresholds and Interpretation

Use age-specific NT-proBNP thresholds: >450 pg/mL for patients <50 years, >900 pg/mL for patients 50-75 years, and >1800 pg/mL for patients >75 years to diagnose heart failure. 3, 4

• For BNP, levels >100 pg/mL have 90% sensitivity for differentiating cardiac from non-cardiac causes of dyspnea, while levels >400 pg/mL more definitively indicate heart failure 2
• BNP levels of 100-500 pg/mL fall in a "grey zone" requiring clinical correlation and further evaluation 2
• NT-proBNP >2000 pg/mL is associated with significantly worse outcomes including increased mortality and heart failure readmissions 3, 4

Initial Management Algorithm for Elevated Levels

Step 1: Urgent Cardiac Evaluation

• Arrange echocardiography within 2 weeks to assess left ventricular ejection fraction and cardiac structure 3, 4
• Refer concurrently for specialist cardiology evaluation 3

Step 2: Comprehensive Laboratory Assessment

• Obtain complete blood count, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, and thyroid-stimulating hormone 1
• Measure troponin if acute coronary syndrome is suspected, particularly when NT-proBNP >1170 ng/L in men or >2150 ng/L in women 4

Step 3: Treatment Based on Ejection Fraction

For Heart Failure with Reduced Ejection Fraction (HFrEF, LVEF ≤40%):

• Initiate quadruple guideline-directed medical therapy: 3, 4
  • ACE inhibitor/ARB or preferably ARNI (sacubitril/valsartan)
  • Beta-blocker
  • Mineralocorticoid receptor antagonist (for NYHA class II-IV)
  • Loop diuretics for congestion/fluid overload
• Administer loop diuretics promptly if fluid overload is present, with initial parenteral dose equal to or exceeding chronic oral daily dose 2
• Titrate all medications to target doses as tolerated 4

For Heart Failure with Preserved Ejection Fraction (HFpEF):

• Focus on treating comorbid conditions: hypertension, ischemic heart disease, and diabetes mellitus 3, 4
• Use diuretics for symptom relief only if fluid overload is present 3, 4

Monitoring Strategy

Serial monitoring of natriuretic peptides is useful for assessing treatment response, with a >30% reduction from baseline indicating good prognosis and adequate therapy. 4

• Monitor serum electrolytes and renal function regularly, especially after initiating or adjusting renin-angiotensin system blockers 3, 4
• Predischarge NT-proBNP is more strongly associated with outcomes than admission levels 4
• BNP-guided therapy can be useful to achieve optimal dosing of guideline-directed medical therapy in select clinically euvolemic patients followed in structured heart failure disease management programs 1
• Daily weights and signs of congestion should be monitored, with diuretic doses titrated based on fluid status and urine output 3

Prognostic Implications

• NT-proBNP levels establish prognosis and disease severity in chronic heart failure 1
• Upper tertile NT-proBNP (>1958 pg/mL) identifies patients at high risk for mortality requiring high-priority management 5
• NT-proBNP >986 pg/mL is associated with higher 1-year mortality risk 4
• In diabetic patients, intensified risk factor treatment when NT-proBNP is elevated reduces hospitalization or death from cardiac disease (HR 0.35,95% CI 0.13-0.98) 4

Critical Confounders and Pitfalls

Natriuretic peptide levels can be elevated in multiple non-heart failure conditions, requiring careful clinical correlation:

• Advanced age: Older patients (>75 years) have higher baseline levels; use age-adjusted thresholds 3, 2, 4
• Atrial fibrillation: May increase BNP/NT-proBNP by 20-30% and changes the NT-proBNP:BNP ratio from 5.75:1 to 8.03:1 2, 6
• Renal dysfunction: Severe renal failure elevates NT-proBNP independent of cardiac function; extremely high levels (4000-20,000 pg/mL) may be driven more by renal dysfunction than heart failure severity 3, 4
• Obesity: BMI >30-35 kg/m² is associated with relatively lower natriuretic peptide levels despite cardiac dysfunction 3, 2, 4
• Other cardiac conditions: Pulmonary embolism (NT-proBNP >500-1000 ng/L identifies higher-risk patients), acute coronary syndrome, right ventricular dysfunction, and cyanotic heart disease 3, 4
• Non-cardiac conditions: Severe COPD, sepsis/septic shock 3, 4
• Medications: ACE inhibitors, ARBs, beta-blockers, and spironolactone reduce natriuretic peptide levels, potentially masking elevation in treated patients 2, 4, 7

Treatment Escalation for Inadequate Response

• If initial diuresis is inadequate, consider higher doses of intravenous loop diuretics, adding a second diuretic (thiazide), or low-dose dopamine infusion 2
• Ultrafiltration may be considered for refractory congestion with obvious volume overload 2
• Intravenous vasodilators (nitroglycerin, nitroprusside, or nesiritide) may be used as adjuncts to diuretic therapy 2
• For persistent symptoms despite optimal medical therapy, consider advanced therapies: cardiac resynchronization therapy, implantable cardioverter-defibrillator, mechanical circulatory support, or heart transplant evaluation 2