Brain Natriuretic Peptide

Aka: Brain Natriuretic Peptide, B-Type Natriuretic Peptide, BNP, NT-proBNP, N-Terminal BNP, ntBNP

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II. Mechanism

  1. Heart secretes natriuretic peptides
    1. Maintains Blood Pressure and Blood Volume
    2. Prevents excessive salt and water retention
  2. Specific activity of natriuretic peptides
    1. Suppresses Sympathetic Nervous System
    2. Suppresses renin-Angiotensin-Aldosterone system
    3. Stimulates diuresis
    4. Decreases Peripheral Vascular Resistance
    5. Increases Smooth Muscle relaxation
  3. Pathway for heart BNP release
    1. Left ventricular wall stretched by volume overload (increased end-diastolic pressure)
    2. Cardiac Muscle Cells secrete BNP precursor (pre-proBNP)
    3. Pre-proBNP converted to proBNP
    4. ProBNP cleaved into 2 parts
      1. C-terminal BNP (biologically active)
      2. N-Terminal BNP or NT-proBNP (biologically inactive)

III. Indication

  1. Congestive Heart Failure Marker
    1. Distinguish acute CHF exacerbation from other acute Dyspnea Causes
      1. Examples: COPD, Pneumonia, Pulmonary Embolism, Acute Coronary Syndrome
    2. Risk stratify CHF exacerbation, identifying low risk patients (with established dry BNP baseline)
      1. Identify who may be appropriate for Emergency Department discharge
    3. Acute CHF prognosis indicator
      1. Decreased rate of readmission or death at 1 year if BNP decreased >50% during hospitalization
      2. Michtalik (2011) Am J Cardiol 107(8): 1191-5 [PubMed]
  2. Dyspnea Evaluation
    1. Most useful for Negative Predictive Value (when evaluating the Dyspnea differential diagnosis)
    2. BNP<50-100 pg/ml (or NT-BNP <300 pg/ml) suggests other Dyspnea cause
    3. BNP >400-500 pg/ml suggests Acute Decompensated Congestive Heart Failure
      1. See below for age-based NT-BNP cutoffs

IV. Precautions

  1. BNP rise may be delayed hours following episode of flash Pulmonary Edema

V. Intrepetation: BNP Levels

  1. No Congestive Heart Failure
    1. BNP <50-100 pg/ml (Median BNP: 9 pg/ml)
    2. NT-BNP <300 pg/ml
  2. Cut-offs suggestive of Acute Dyspnea due to CHF
    1. BNP >400 pg/ml (Test Sensitivity: 82%, Test Specificity: 83%)
    2. NT-proBNP cut-offs based on age
      1. Age <50 years old: NT-BNP >450 pg/ml
      2. Age 50-75 years old: NT-BNP >900 pg/ml
      3. Age >75 years old: NT-BNP >1800 pg/ml
  3. Cut-offs in Obesity
    1. BNP levels are lower in obese patients (even with Heart Failure)
    2. BMI >35.0 kg/m2
      1. BNP >50 pg/ml is consistent with Heart Failure
    3. BMI >35.0 kg/m2
      1. Double the lab resulted BNP and use standardized cutoff for interpretation (i.e. >100 pg/ml)
    4. References
      1. Maisel (2008) Eur J Heart Fail 10(9):824-39 [PubMed]
  4. Median BNPs for each Congestive Heart Failure class
    1. NYHA Class I CHF: Median BNP 83 pg/ml (49-137)
    2. NYHA Class II CHF: Median BNP 235 pg/ml (137-391)
    3. NYHA Class III CHF: Median BNP 459 pg/ml (200-871)
    4. NYHA Class IV CHF: Median BNP 1119 pg/ml (>728)
  5. Marker of mortality and cardiovascular events in the next 2-3 months
    1. BNP >200 pg/ml (goal <100 pg/ml)
    2. nt-BNP > 5180 pg/ml (goal <1700 pg/ml)
  6. Outpatient goals associated with lower exacerbation and hospitalization rates as well as mortality
    1. BNP <100 pg/ml
    2. nt-BNP <1700 pg/ml
  7. References
    1. Chen (2010) Heart 96(4): 314-20 [PubMed]

VI. Causes: Increased BNP level

  1. Congestive Heart Failure
    1. BNP released from left ventricle
    2. Response to volume overload, pressure overload (increased end diastolic pressure)
    3. Chronic Heart Failure (establish a "dry" BNP baseline)
  2. Left Ventricular Hypertrophy
  3. Cardiac inflammation
    1. Myocarditis
    2. Cardiac Allograft rejection
  4. Kawasaki Disease
  5. Primary Pulmonary Hypertension
  6. Renal Failure
    1. Avoid in Dialysis dependent patients unless there is a well-established BNP baseline
  7. Ascitic Cirrhosis
  8. Endocrine disease
    1. Primary Hyperaldosteronism
    2. Cushing Syndrome
  9. Age over 60 years old
  10. Women
  11. Medications that raise BNP
    1. Digoxin
    2. Beta Blockers (some)

VII. Causes: Artificially lowered BNP levels

  1. Diuretics (e.g. Spironolactone)
  2. ACE Inhibitors
  3. Angiotensin Receptor Blockers (ARBs)
  4. Obesity
    1. Consider doubling BNP level when Body Mass Index is >35
  5. Diastolic Dysfunction (Heart Failure with Preserved Ejection Fraction)
  6. Flash Pulmonary Edema with BNP obtained <1 hour (prior to BNP rise)

VIII. Efficacy

  1. Most effective for Negative Predictive Value
    1. See above under indications
    2. CHF very unlikely if BNP<50 pg/ml
  2. Primarily used in adults, but may be used in children with established cardiac disease
    1. Consider in children with known cardiac disease with acute illness resulting in Dyspnea
    2. BNP normal ranges are similar to adults
    3. Mayer (2008) Pediatrics 121(6):e1484-8 +PMID: 18519452 [PubMed]
  3. Trending does not offer benefit over usual care for inpatient CHF management
    1. Felker (2017) JAMA 318(8): 713-20 +PMID:28829876 [PubMed]

IX. References

  1. Pang (2014) Crit Dec Emerg Med 28(9): 9-17
  2. Cheng (2001) J Am Coll Cardiol 37:386-91 [PubMed]
  3. Collins (2003) Ann Emerg Med 41:532-45 [PubMed]
  4. Dao (2001) J Am Coll Cardiol 37:379-85 [PubMed]
  5. Doust (2004) Arch Intern Med 164:1978-84 [PubMed]
  6. Mueller (2004) N Engl J Med 350:647-54 [PubMed]
  7. Wieczorek (2002) Am Heart J 144:834-9 [PubMed]

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