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B-Natriuretic Peptide

Policy Number: MP-142

Latest Review Date: August 2019

Category: Laboratory

Policy Grade: Active Policy but no longer scheduled for regular literature reviews and updates.


Brain natriuretic peptide (BNP) is a 32-amino acid polypeptide and is classed a cardiac neurohormone that is secreted by the ventricles of the heart in response to volume expansion and pressure overload. The peptide was first isolated from a porcine brain in 1988 and later from the cardiac ventricles of porcine, rat and humans.

There are three major natriuretic peptides; atrial natriuretic peptide (ANP), Brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Both ANP and BNP are released from the ventricles both before and during the stretch of volume expansion and pressure of overload. BNP shows the most promise for diagnostic and prognostic marker of cardiac dysfunction. BNP release appears to be in direct response to ventricular volume stretch and pressure overload. The most widely investigated use for BNP has been in heart failure (HF). Measurement of BNP is a highly sensitive and moderately specific method of differentiating heart failure from other non-cardiac causes of dyspnea. Blood levels of BNP are elevated in heart failure.


Effective for dates of service on or after August 13, 2019:

The measurement of plasma brain natriuretic peptide (BNP) or NT-proBNP may be considered medically necessary for any of the following indications:

  • Diagnosis of heart failure in a patient with dyspnea; OR
  • Differentiating dyspnea due to heart failure from pulmonary disease, especially when the etiology of dyspnea is unclear; OR
  • Establishing a prognosis or disease severity in patients diagnosed with chronic heart failure; OR
  • Monitoring response to treatment for heart failure to achieve optimal dosing of guideline directed medical therapy

Plasma brain natriuretic peptide (BNP) or NT-proBNP testing is considered not medically necessary and investigational for all other indications, including risk assessment.

Effective for dates of service previous to August 13, 2019:

B-natriuretic peptide is considered not medically necessary and investigational.


Congestive heart failure (CHF) is the fourth leading cause of adult hospitalizations in the United States and affects five million Americans with 500,000 new cases each year (Maisel, 2002). 800,000 are hospitalized each year with 300,000 deaths. For patients over the age of 65, congestive heart failure is the leading cause of hospitalization and accounts for 3% to 5% of the health care budget.

When BNP is cleaved from its precursor (proBNP), N-terminal proBNP (NT-proBNP) is released. Maisel et al published the in the New England Journal of Medicine. In this study, 1586 emergency department patients with a major complaint of acute dyspnea had BNP levels drawn at bedside and received complete evaluation by the emergency department physician. Plasma BNP was higher in patients with clinically diagnosed heart failure compared to those without heart failure. Two independent cardiologists that examined all clinical information except the BNP levels verified the diagnosis of CHF. BNP levels were more accurate for diagnosing HF at 83.4%, negative predictive value was 96%. The conclusion was that when combined with other clinical information, rapid BNP levels are more useful in establishing or excluding the diagnosis of CHF in patients with acute dyspnea.

BNP is a neurohormone synthesized predominantly in ventricular myocardium and is released into circulation in response to ventricular dilatation and pressure overload. Plasma levels of BNP elevates in patients with congestive heart failure and increases in proportion to the degree of left ventricular dysfunction and the severity of symptoms of heart failure. DeLemos et al measured plasma BNP levels in over 2500 patients from 40 ± 20 hours after the onset of ischemic symptoms. The plasma levels correlated with the risk of death, heart failure, and myocardial infarction at 30 days and ten months. The base line outcomes were higher among patients who died than among those who were alive at 30 days. They concluded that a single measurement of BNP obtained in the first few days after the onset of ischemic symptoms, provides predictive information for use in risk stratification across the spectrum of acute coronary syndromes. This suggests that BNP should be measured after an acute coronary syndrome in order to identify patients at high and low risk for adverse outcomes and that treatment should be adjusted accordingly.

Measurement of natriuretic peptides (i.e., BNP and NT-proBNP) can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of heart failure is uncertain. Measurement of natriuretic peptides can be useful in risk stratification. But it should be cautioned that, although elevated natriuretic peptide levels may help confirm a suspected diagnosis of heart failure, the results of this testing alone should not be used to confirm or exclude a heart failure diagnosis.

Available commercial assays for plasma BNP or NT-proBNP actually measure mixtures of peptides. Plasma BNP assays appear to detect various degradation products of BNP as well as proBNP. Assays for NT-proBNP likely also detect proBNP. The relative contribution of individual natriuretic peptides has not yet been made clear. Plasma BNP and NT-proBNP concentrations can be skewed in patients who suffer from comorbidities including renal failure, obesity, coronary artery disease, valvular heart disease, pulmonary hypertension, and sepsis. The value of measuring natriuretic peptides in this population cannot be proven beneficial and medically necessary.

Summary of Evidence

Clerico et al cites that biological variation of BNP should not be interpreted strictly as there is random fluctuation noted and the results should not be directly transferred into clinical practice. More accurate studies are needed to prove the utility of this technology at this time. The evidence is insufficient to support the measurement of BNP in risk stratification.

There is evidence based on the Breathing Not Properly study (Maisel et al) that the accuracy of plasma BNP for heart failure has clinical utility in the diagnosis and assessment of severity of congestive heart failure. The predictive accuracy of plasma BNP for heart failure was equivalent to or better than other parameters (i.e. chest xray, rales of physical examination, NHANES and Framingham criteria) for the diagnosis of heart failure. The evidence is sufficient to support the measurement of BNP in certain situations for the purposes of diagnosis and evaluation of congestive heart failure.

Practice Guidelines and Position Statements

Guidelines from the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) list as a class I recommendation the use of BNP or NT-proBNP values in the diagnosis of heart failure in ambulatory patients with dyspnea, especially when the diagnosis is uncertain, as well as their use in establishing the prognosis or disease severity in ambulatory patients with chronic heart failure. The guidelines assign a class IIa recommendation to the use of BNP or NT-proBNP in determining optimal dosing for select ambulatory patients who are clinically euvolemic and are undergoing medical therapy in a well-structured heart-failure management program.

For hospitalized/acute patients, the ACCF/AHA guidelines list as a class I recommendation the use of BNP or NT-proBNP in the diagnosis of acutely decompensated heart failure, especially when the diagnosis is uncertain, as well as the use of BNP or NT-proBNP and/or cardiac troponin in establishing the prognosis or disease severity of acutely decompensated heart failure in such patients. However, the guidelines state that the usefulness of BNP or NT-proBNP in guiding therapy in hospitalized/acute patients with acutely decompensated heart failure has not been well established.

U.S. Preventative Services Task Force

Not applicable.


Brain natriuretic peptide, B-natriuretic peptide, BNP, heart failure, HF, congestive heart failure, CHF, dyspnea, ANP, atrial natriuretic peptide, NT-proBNP, N-terminal pro-BNP, C-type natriuretic peptide, CNP


A number of devices have received FDA 510(k) approval for evaluating circulating BNP and NT-proBNP levels. These devices can be found on the FDA Center for Devices and Radiological Health 510(k) database. An example of an FDA-approved BNP device is the Triage® B-Type Natriuretic Peptide (BNP) Test (Biosite, Inc., San Diego, CA). The test is intended to be used as an aid in the following (FDA, 2005):

  • diagnosis of heart failure
  • assessment of heart failure severity
  • risk stratification of patients with acute coronary syndromes (ACS)
  • risk stratification of patients with heart failure

The clinical supportive data in the 510(k) substantial equivalence determination decision summary device only template states the sponsor provided five peer-reviewed articles assessing the clinical utility of BNP measurements as an aid in the risk stratification of patients with heart failure. The references are not listed for the five articles but can be found in the sponsor labeling. The decision summary states that a systematic review by Doust et al (2005) included the five articles previously mentioned which concluded that BNP was a strong prognostic indicator for patients with heart failure (FDA, 2005).

An example of a NT-proBNP test system is the Elecsys® proBNP Immunoassay (Roche Diagnostics Corporation, Indianapolis, IN). The intended use is as an aid in the diagnosis of individuals suspected of having CHF. The test is further indicated for the risk stratification of patients with ACS and CHF. Three peer-reviewed studies are listed as clinical supportive data in the 510(k) substantial equivalence determination decision summary device only template including James et al (2003), Jernberg et al (2002), and Fisher et al (2003) (FDA, 2003).


Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. Special benefit consideration may apply. Refer to member’s benefit plan.


CPT codes:


Natriuretic peptide


  1. Biosite, Inc. Triage BNP Test,
  2. Cataliotti A, Malatino LS, Jougasaki M, Zoccali C, Castellino P, Giacone G, Bellanuova I, Tripepi R, Seminara G, Parlongo S, Stancanelli B, Bonanno G, Fatuzzo P, Rapisarda F, Belluardo P, Signorelli SS, Heublein DM, Lainchbury JG, Leskinen HK, Bailey KR, Redfield MM, Burnett JC Jr. Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling. Mayo Clin Proc. 2001;76(11):1111.
  3. Chavey II, William E., et al. Cover article: Cardiovascular medicine update, American Family Physician, September 2001, Vol. 64, No. 5.
  4. Clerico A, Carlo Zucchelli G, Pilo A, Passino C, Emdin M. Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay. Laboratory of Cardiovascular Endocrinology and Cell Biology, CNR Institute of Clinical Physiology, Pisa, Italy.
  5. Clerico A, Del Ry S, Giannessi D. Measurement of cardiac natriuretic hormones (atrial natriuretic peptide, brain natriuretic peptide, and related peptides) in clinical practice: the need for a new generation of immunoassay methods. Clin Chem. 2000;46(10):1529.
  6. Cohn, Jay. Valsartan heart failure trial (Val-HeFT), American College of Cardiology,
  7. Collins, Sean P., Ronan-Bentle, Sarah and Storrow, Alan B. Diagnostic and prognostic usefulness of natriuretic peptides in emergency department patients with dyspnea, Annals of Emergency Medicine, April 2003, Vol. 41, No.
  8. Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH Jr, de Lemos JA. Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation. 2005;112(14):2163.
  9. DeLemos James A, Morrow David A, et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes, The New England Journal of Medicine, October 2001, Vol. 345, No. 14.
  10. Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol. 2006;47(1):85. Epub 2005 Dec 15.
  11. Hunt, Sharon A, et al. ACC/AHA Guidelines for the evaluation and management of chronic heart failure in the adult, Journal of the American College of Cardiology, December 2001.
  12. Hunt SA, Abraham WT, Chin MH, Feldman AM, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult—summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration with the American College of Chest physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society. Circulation 2005; 112: 1825-1852.
  13. Jessup M, Abraham WT, et al. 2009 Focused Update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation, 2009; 119:1977-2016.
  14. Kinnunen P, Vuolteenaho O, Ruskoaho H. Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching. Endocrinology. 1993;132(5):1961.
  15. Kistorp Caroline, Raymond Ilan, et al. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults, JAMA, April 2005, Vol. 293, No. 13.
  16. Maisel, Alan S. B-Type natriuretic peptide (BNP) levels: Diagnostic and therapeutic potential, Reviews in Cardiovascular Medicine, 2001, Vol. 2, Suppl. 2
  17. Maisel, Alan S., et al. Rapid measurement of B-Type natriuretic peptide in the emergency diagnosis of heart failure, The New England Journal of Medicine, July 2002, Vol. 347, No. 3, pp. 161-167.
  18. Maisel, Alan. B-Type natriuretic peptide in the diagnosis and management of congestive heart failure, Cardiology Clinics, November 2001, Vol. 19, No. 4.
  19. McCord J, Mundy BJ, Hudson MP, Maisel AS, Hollander JE, Abraham WT, Steg PG, Omland T, Knudsen CW, Sandberg KR, McCullough PA. Relationship between obesity and B-type natriuretic peptide levels. Arch Intern Med. 2004;164(20):2247.
  20. McCullough PA, Duc P, Omland T, McCord J, Nowak RM, Hollander JE, Herrmann HC, Steg PG, Westheim A, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS. B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study. Am J Kidney Dis. 2003;41(3):571.
  21. Mehra MR, Uber PA, Park MH, Scott RL, Ventura HO, Harris BC, Frohlich ED. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol. 2004;43(9):1590.
  22. Miller, Karl E. BNP as a screen for heart failure in the general public?, American Family Physician, June 2003.
  23. Mohideen, M.R. Brain natriuretic peptide is more than a marker, Ceylon Medical Journal, September 2002, Vol. 47, No. 3.
  24. Mueller C, Laule-Kilian K, Scholer A, Nusbaumer C, Zeller T, Staub D, Perruchoud AP. B-type natriuretic peptide for acute dyspnea in patients with kidney disease: insights from a randomized comparison. Kidney Int. 2005;67(1):278.
  25. Nielsen, Olav W., McDonagh, Theresa A., et al. Retrospective analysis of the cost-effectiveness of using plasma brain natriuretic peptide in screening for left ventricular systolic dysfunction in the general population, Journal of the American College of Cardiology, 2003, Vol. 41, No. 1.
  26. Schillinger Martin. Cardiovascular risk stratification in older patients: role of brain natriuretic peptide, C-reactive protein, and urinary albumin levels, JAMA 2005; 293: 1667-1669.
  27. Takami Y, Horio T, Iwashima Y, Takiuchi S, Kamide K, Yoshihara F, Nakamura S, Nakahama H, Inenaga T, Kangawa K, Kawano Y. Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF. Am J Kidney Dis. 2004;44(3):420.
  28. U.S. Food and Drug Administration. New device clearance: Elecsys® proBNP immunoassay – K022516,
  29. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004;109(5):594.
  30. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J AM Coll Cardiol 2013 Oct 12. 62 (16):e147-239.


Medical Policy Group, February 2004

Medical Policy Administration Committee, March 2004

Available for comment February 27-April 12, 2004

Medical Policy Group, December 2005 (2)

Medical Policy Administration Committee, December 2005

Available for comment December 27, 2005-February 9, 2006

Medical Policy Group, January 2007 (1)

Medical Policy Group, January 2009 (1)

Medical Policy Group, September 2011 (3): Updated Key Points & References

Medical Policy Group, September 2012 (3): Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, October 2013 (3): Removed ICD-9 Diagnosis codes; no change to policy statement.

Medical Policy Group, June 2019 (9): Updates to Description, Key Points, Approved by Governing Bodies, References. Added key words: ANP, atrial natriuretic peptide, NT-proBNP, N-terminal pro-BNP, C-type natriuretic peptide, CNP. No change to policy statement.

Medical Policy Group, August 2019 (9): Updates to Key Points. Policy statement modified to open coverage for certain situations, denoted in policy section, effective 8/13/2019.

Available for comment August 13, 2019 through September 27, 2019.

Medical Policy Administration Committee, August 2019.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.