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]

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Ontology: Nesiritide (C0054015)

Definition (NCI) Brain natriuretic peptide 32 (32 aa, ~3 kDa) is encoded by the human NPPB gene. This protein plays a role in the modulation of diuresis, vasorelaxation and secretion of renin and aldosterone.
Definition (NCI) A recombinant version of the cardiac neurohormone, human B-type natriuretic peptide (hBNP) produced by the ventricular myocardium. Nesiritide binds to natriuretic peptide receptors on vascular smooth muscle and endothelial cells, through which it triggers guanylate cyclase dependent signal transduction resulting in increase of intracellular concentrations of cGMP. This leads to smooth muscle cell relaxation causing arterial and venous dilatation.
Definition (MSH) A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.
Definition (PDQ) A recombinant version of the cardiac neurohormone, human B-type natriuretic peptide (hBNP) produced by the ventricular myocardium. Nesiritide binds to natriuretic peptide receptors on vascular smooth muscle and endothelial cells, through which it triggers guanylate cyclase dependent signal transduction resulting in increase of intracellular concentrations of cGMP. This leads to smooth muscle cell relaxation causing arterial and venous dilatation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=434520&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=434520&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C47636" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Hormone (T125)
MSH D020097
SnomedCT 385678006, 385677001, 385680000, 385679003, 407059007
English Nesiritide (HBNP), 1,2-Dithia-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50-hexadecaazacyclotripentacontane, Cyclic Peptide Derivative, L-Histidine, L-seryl-L-prolyl-L-lysyl-L-methionyl-L-valyl-L-glutaminylglycyl-L-serylglycyl-L-cysteinyl-L-phenylalanylglycyl-L-arginyl-L-lysyl-L-methionyl-L-alpha-aspartyl-L-arginyl-L-isoleucyl-L-seryl-L-seryl-L-seryl-L-serylglycyl-L-leucylglycyl-L-cysteinyl-L-lysyl-L-valyl-L-leucyl-L-arginyl-L-arginyl-, Cyclic (10-26)-disulfide, Human Brain Natriuretic Factor-32, Natriuretic factor-32, Natriuretic factor, brain, Brain Natriuretic Peptide, Natriuretic Peptide, Brain, Peptide, Brain Natriuretic, nesiritide (medication), nesiritide, Nesiritide, NESIRITIDE, Natriuretic Peptide, Brain [Chemical/Ingredient], b-type natriuretic peptide, brain natriuretic peptides, brain natriuretic peptide, b type natriuretic peptide, b type natriuretic peptides, brain natriuretic factor, type b natriuretic peptide, Brain Natriuretic Peptide 32, BNP(1-32), Human B-type natriuretic peptide (substance), BNP-32, B-Type Natriuretic Peptide, BNP 32, BNP Gene Product, Brain Natriuretic Peptide-32, Natriuretic Factor 32, Natriuretic Factor-32, Natriuretic Peptide Type B, Natriuretic Peptide Type-B, Natriuretic Peptide, B-Type, Natriuretic Peptide, Type-B, Natriuretic Peptide-32, Brain, Peptide-32, Brain Natriuretic, Type-B Natriuretic Peptide, Type B Natriuretic Peptide, Human B-type natriuretic peptide (product), Human B-type natriuretic peptide, Nesiritide (product), Nesiritide (substance), Brain natriuretic peptide (substance), Natriuretic Peptide B Type, B-type natriuretic peptide, Brain natriuretic peptide
Portuguese Peptídeo Encefálico Natriurético, Peptídeo Natriurético Encefálico, Peptídeo Natriurético Cerebral, Peptídeo Cerebral Natriurético, Nesiritida
Spanish Péptido Natriurético Encefálico, Péptido Encefálico Natriurético, péptido natriurético cerebral humano de tipo B, nesiritide (sustancia), nesiritide, nesiritida (sustancia), péptido natriurético humano tipo B (sustancia), Péptido Cerebral Natriurético, Péptido Natriurético Cerebral, nesiritida (producto), nesiritida, péptido natriurético humano tipo B (producto), péptido natriurético humano tipo B, péptido natriurético cerebral (sustancia), péptido natriurético cerebral, péptido natriurético tipo B, Nesiritida
Swedish Natriuretisk peptid, hjärna
Czech natriuretický peptid typu B, B-natriuretický peptid, natriuretický peptid B, BNP, mozkový natriuretický peptid, nesiritid
Finnish B-tyypin natriureettinen peptidi
French Facteur natriurétique de type B, BNP-32, Peptide cérébral natriurétique, Peptide natriurétique de type B, Nésiritide, BNP32, BNP (Brain Natriuretic Peptide), Peptide natriurétique cérébral, Produit du gène BNP
Russian NATRIIURETICHESKII PEPTID MOZGA, MOZGA GOLOVNOGO NATRIIURETICHESKII PEPTID, NATRIIURETICHESKII PEPTID MOZGOVOI, НАТРИЙУРЕТИЧЕСКИЙ ПЕПТИД МОЗГОВОЙ, НАТРИЙУРЕТИЧЕСКИЙ ПЕПТИД МОЗГА, МОЗГА ГОЛОВНОГО НАТРИЙУРЕТИЧЕСКИЙ ПЕПТИД
Japanese 脳性ナトリウム利尿ペプタイド, 脳性利尿ペプチド, ナトリウム利尿ペプチド-脳性, 脳ナトリウム利尿ペプチド, 脳内ナトリウム利尿ペプチド, ナトリウム利尿ペプチド-B型, クエン酸ネシリチド, 脳性ナトリウム利尿ペプチド, ネシリチド, ネシリチドクエン酸塩, B型ナトリウム利尿ペプチド
Polish Peptyd natriuretyczny mózgowy
Croatian MOŽDANI NATRIJURETSKI PEPTID, NATRIURETSKI PEPTID, MOŽDANI, NATRIJURETSKI PEPTID, MOŽDANI
Norwegian Natriuretisk faktor-32, Type-B-natriuretisk peptid, Natriuretisk peptid type-B, Nesiritid, Natriuretisk peptid, hjerne, Hjernenatriuretisk peptid, B-type natriuretisk peptid, BNP-32
German Gehirn, natriuretisches Peptid, Natriuretisches Peptid, Gehirn
Italian Peptide natriuretico del cervello

Ontology: NPPB gene (C1417808)

Definition (NCI) This gene is involved in cardiac homeostasis.
Concepts Gene or Genome (T028)
English BNP, NPPB, NATRIURETIC PEPTIDE, BRAIN TYPE, NATRIURETIC PEPTIDE PRECURSOR B, NPPB Gene, Natriuretic Peptide Precursor B Gene, natriuretic peptide B, NPPB gene

Ontology: N-terminal prohormone brain natriuretic peptide (C2242501)

Concepts Laboratory Procedure (T059)
English N-terminal prohormone brain natriuretic peptide
Spanish Prohormona N-terminal del péptido natriurético cerebral
German N-terminales Prohormon von BNP
Japanese ノウセイナトリウムリニョウペプチドゼンクタイNタンフラグメント, 脳性ナトリウム利尿ペプチド前駆体N端フラグメント
Czech N-terminální natriuretický peptid mozkového prohormonu
Portuguese Peptídeo natriurético cerebral prohormona N-terminal
Dutch N-terminal prohormoon hersenen natriuretische peptide
Italian Frammento N-terminale del proormone del peptide natriuretico cerebrale
French Propeptide cérébral natriurétique N-terminal
Hungarian N-terminalis prohormon agyi natriuretikus peptidje