Latest Review Date: August 2024

Category: Laboratory

POLICY:

The measurement of plasma brain natriuretic peptide (BNP) or N-terminal proBNP (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 N-terminal proBNP (NT-proBNP) testing is considered investigational for all other indications, including risk assessment.

DESCRIPTION OF PROCEDURE OR SERVICE:

Brain natriuretic peptide (BNP) is a 32-amino acid polypeptide cardiac neurohormone. It 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. BNP is biologically active as a hormone. N-terminal proBNP (NT-proBNP) is cleared passively from the body and is not biologically active. Both will show elevated levels in the presence of heart failure. The half‐life of BNP is much shorter than NT‐proBNP, which explains why NT‐proBNP serum values are higher than BNP values, even though both molecules are released in equimolar proportions.

Although kidney failure, pulmonary embolism, pulmonary hypertension, sepsis, and lung problems can cause high BNP levels, the most widely investigated use for BNP has been in heart failure. BNP release appears to be in direct response to ventricular volume stretch and pressure overload. Measurement of BNP is a highly sensitive and moderately specific method of differentiating heart failure from other non-cardiac causes of dyspnea. BNP testing is often performed in the emergency room when there is suspicion of heart failure so treatment can be started as soon as possible.

KEY POINTS:

This policy has been updated with literature review performed through August 1, 2024.

Summary of Evidence

When combined with other clinical information, BNP and NT-proBNP levels are useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea. Another clinically significant use of BNP and NT-proBNP measurement is when used in the presence of acute coronary syndrome. Patients can be identified as at high and low risk for adverse outcomes so treatment should be adjusted accordingly. The evidence is sufficient to support that the technology, when used for the purposes of diagnosis and evaluation of congestive heart failure as defined in this evidence review, results in an improvement in net health outcomes.

BNP and NT-proBNP concentrations can be skewed in patients who suffer from comorbidities including diabetes, 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. A 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 to support the measurement of plasma brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in risk stratification. The evidence is insufficient to support that the technology results in an improvement in net health outcomes when used for risk stratification.

Practice Guidelines and Position Statements

American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)

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.

KEY WORDS:

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

APPROVED BY GOVERNING BODIES:

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.

BENEFIT APPLICATION:

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

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

CPT codes:

REFERENCES:

1. Chavey WE 2nd, Blaum CS, Bleske BE, Harrison RV, Kesterson S, Nicklas JM. Guideline for the management of heart failure caused by systolic dysfunction: Part I. Guideline development, etiology and diagnosis. Am Fam Physician. 2001 Sep 1; 64(5):769-74.
2. 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. Clin Chem Lab Med. 2006; 44(4):366-78.
3. 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 Oct; 46(10):1529-34. 
4. Collins SP, Ronan-Bentle S, Storrow AB. Diagnostic and prognostic usefulness of natriuretic peptides in emergency department patients with dyspnea. Ann Emerg Med. 2003 Apr; 41(4):532-45. 
5. de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, Hall C, Cannon CP, Braunwald E. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med. 2001 Oct 4; 345(14):1014-21.
6. Doust J, Lehman R, Glasziou P. The role of BNP testing in heart failure. Am Fam Physician. 2006 Dec 1; 74(11):1893-8.
7. Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol. 2006 Jan 3; 47(1):85-90.
8. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: 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 Sep 20; 112(12):e154-235.
9. Hunt, S. A., Baker, D. W., Chin, M. H., Cinquegrani, M. P., Feldman, A. M., Francis, G. S., Ganiats, T. G., Goldstein, S., Gregoratos, G., Jessup, M. L., Noble, R. J., Packer, M., Silver, M. A., Stevenson, L. W., Gibbons, R. J., Antman, E. M., Alpert, J. S., Faxon, D. P., Fuster, V., Jacobs, A. K., … American College of Cardiology/American Heart Association (2001). ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Journal of the American College of Cardiology, 38(7), 2101–2113.
10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
11. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, Konstam MA, Mancini DM, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 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 Apr 14; 119(14):1977-2016.
12. Kinnunen P, Vuolteenaho O, Ruskoaho H. Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching. Endocrinology. 1993 May; 132(5):1961-70.
13. Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA. 2005 Apr 6; 293(13):1609-16.
14. Lee JE, Choi SY, Huh W, Park SW, Kim DJ, Oh HY, Kim YG. N-terminal pro-brain natriuretic peptide levels predict left ventricular systolic function in patients with chronic kidney disease. J Korean Med Sci. 2009 Jan; 24 Suppl (Suppl 1):S63-8.
15. Maisel A. B-type natriuretic peptide levels: diagnostic and prognostic in congestive heart failure: what's next? Circulation. 2002 May 21; 105(20):2328-31. 
16. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA; Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002 Jul 18; 347(3):161-7.
17. Maisel AS. B-type natriuretic peptide (BNP) levels: diagnostic and therapeutic potential. Rev Cardiovasc Med. 2001; 2 Suppl 2:S13-8.
18. McCord J, Mundy BJ, Hudson MP, Maisel AS, Hollander JE, Abraham WT, Steg PG, Omland T, Knudsen CW, Sandberg KR, McCullough PA; Breathing Not Properly Multinational Study Investigators. Relationship between obesity and B-type natriuretic peptide levels. Arch Intern Med. 2004 Nov 8; 164(20):2247-52. 
19. 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 May 5; 43(9):1590-5.
20. Mohideen, M.R. Brain natriuretic peptide is more than a marker. Ceylon Medical Journal, 2002 Sept; 47(3).
21. 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 Jan; 67(1):278-84.
22. Nielsen OW, McDonagh TA, Robb SD, Dargie HJ. Retrospective analysis of the cost-effectiveness of using plasma brain natriuretic peptide in screening for left ventricular systolic dysfunction in the general population. J Am Coll Cardiol. 2003 Jan 1; 41(1):113-20.
23. Node K, Inoue T, Boyko V, Goldberg I, Fisman EZ, Adler Y, Schwammenthal E, Matas Z, Behar S, Tenenbaum A. Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment. Cardiovasc Diabetol. 2009 Jan 28; 8:5.
24. Paniagua R, Amato D, Mujais S, Vonesh E, Ramos A, Correa-Rotter R, Horl WH. Predictive value of brain natriuretic peptides in patients on peritoneal dialysis: results from the ADEMEX trial. Clin J Am Soc Nephrol. 2008 Mar; 3(2):407-15.
25. Schillinger M. Cardiovascular risk stratification in older patients: role of brain natriuretic peptide, C-reactive protein, and urinary albumin levels. JAMA. 2005; 293: 1667-1669.
26. Taki M, Hoshide S, Kono K, Kario K. Correlation between B-Type Natriuretic Peptide and N-Terminal pro-B-Type Natriuretic Peptide in a Large Japanese Population at Risk of Stage A Heart Failure. Pulse (Basel). 2018 Jul; 6(1-2):1-8.
27. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004 Feb 10; 109(5):594-600.
28. Weber M, Hamm C. Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart. 2006 Jun; 92(6):843-9.
29. Wong M, Staszewsky L, Latini R, Barlera S, Glazer R, Aknay N, Hester A, Anand I, Cohn JN. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J Am Coll Cardiol. 2004 Jun 2; 43(11):2022-7. 
30. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15; 128(16):1810-52.

POLICY HISTORY:

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.

Medical Policy Group, August 2021 (9): Policy statement updated to remove “not medically necessary,” added N-terminal proBNP description to abbreviation “NT-proBNP” no change to policy intent. Updates to Key Points, Description, References.

Medical Policy Group, October 2021 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, July 2022 (9): Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Updates to Description and Key Points.

Medical Policy Group, August 2023 (5): Updates to Key Points and Benefit Application. No change to Policy Statement. Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, March 2024 (5): Minor update to Key Points. No change to Policy Statement.

Medical Policy Group, August 2024 (5): Minor update to Key Points. No change to Policy Statement. Reviewed by consensus. No new published peer-reviewed literature is available that would alter the coverage statement in this policy.

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.