LCD L34410

Coverage Guidance

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862(a)(1)(D) addresses items related to research and experimentation.

42 CFR §410.32(a) indicates that diagnostic tests may only be ordered by the treating physician (or other treating practitioner acting within the scope of his or her license and Medicare requirements).

CMS Internet-Only Manual, Pub 100-02, Medicare Benefit Policy Manual, Chapter 6, §20.4.1 Diagnostic Services Defined

CMS Manual System, Pub 100-20, One-Time Notification, Transmittal 477, dated April 24, 2009, Change Request 6338

Indications and Limitations of Coverage

B-type natriuretic peptide (BNP) and its precursor amino terminal (NT-proBNP) increase in patients with cardiac disease due to myocardial stress and volume overload as found in heart failure (HF).3

When used in conjunction with other clinical information, the rapid measurement of levels of BNP or NT-proBNP is useful in establishing or excluding the diagnosis of HF as well as assessing the severity of HF in patients with acute dyspnea so that appropriate and timely treatment can be initiated.8

This test may also be used to predict the long-term risk of cardiac events or death across the spectrum of acute coronary syndromes when measured in the first few days after an acute coronary event.9

There is no conclusive evidence currently to warrant the repeated or serial use of BNP or NT-proBNP to alter or monitor treatment of HF especially in hospital inpatients.16 Therefore, repeated or serial use of BNP or NT-proBNP measurements for monitoring and management of CHF are not a covered service.17

The measurement of BNP as part of cardiovascular risk assessment panels, consisting of various combinations of biochemical, immunologic, hematologic, and molecular tests, is considered screening when performed on an asymptomatic patient, and, as such, is not a covered Medicare benefit. Please refer to MolDX: Biomarkers in Cardiovascular Risk Assessment L36129 Local Coverage Determination (LCD).

Summary of Evidence

An estimated 92 million United States (US) adults have at least 1 type of cardiovascular disease (CVD) with estimates that over 40% of the US adult population is projected to have some form of CVD by 2030.5 HF is a multifactorial systemic disease which affects over 26 million people worldwide and is increasing in prevalence.4 Due to its high morbidity and mortality, the correct diagnosis of HF and cardiac dysfunction is paramount to determine appropriate treatment regimens.

Atrial natriuretic peptide (ANP), BNP and C-type natriuretic peptide (CNP) constitute the human natriuretic peptide family. BNP was originally isolated in pig brain tissue but was also found in the cardiac ventricles and to a lesser extent in the atria. Prior to its activation BNP and NT-proBNP are stored as a 108 amino acid polypeptide precursor proBNP in the ventricles. In response to volume expansion/overload and myocyte stretch, proBNP is cleaved to produce the biologically active 32 amino acid BNP and the 76 amino acid peptide NT-proBNP which are released into the vascular system where they can be detected.1,2

The strongest indication for BNP measurement is distinguishing between cardiogenic and non-cardiogenic causes of dyspnea in an emergent setting. An elevated BNP level may indicate the need for further cardiac workup to determine the etiology of the patient’s symptoms.10

A systematic review and meta-analysis of 19 studies involving 22 patient populations with a total of 9093 patients by Battaglia et al. in 200611 concluded that the use of BNP tests to rule out HF in different populations ranging from asymptomatic patients in a community setting to patients presenting with acute dyspnea to the emergency department found that negative results accurately rule out the diagnosis of HF especially if patients are at a relatively low risk of HF. B-type natriuretic peptide tests have the potential to guide clinical decisions, particularly in patients at lower risk in primary care and emergency departments. Applied early in the diagnostic process in patients with suspected cardiac failure, negative BNP test findings can help rule out HF and thus, avoid unnecessary referral to echocardiography. If the test result is positive, confirmation by echocardiography will generally be required. Early diagnosis of left ventricular dysfunction or HF can improve the prognosis of patients with left ventricular dysfunction without overt HF and patients with symptomatic HF.

According to the guidelines of the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) and the European Society of Cardiology, BNP and NT-proBNP are considered the most valuable and reliable biomarkers for diagnosing HF and cardiac dysfunction.6,7

Tsutsui et al.13 in the Japanese Circulation Society/Japanese Heart Failure Society 2021 Guidelines state: ”In the diagnosis of heart failure patients should be examined first for symptoms, medical history, family history, physical findings, electrocardiogram, and chest radiographic findings. Next, the concentration of BNP or NT-BNP in the blood should be determined.”

A review article and joint scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society in 2023 the following strong evidence consensus statements are noted: 1) In patients presenting with dyspnea, measurement of BNP or NT-proBNP is useful to support a diagnosis or exclusion of HF; 2) In patients with chronic HF, measurements of BNP or NT-proBNP levels are recommended for risk stratification; 3) In patients hospitalized for HF, measurement of BNP or NT-proBNP levels at admission is recommended to establish prognosis.14

Krauser D. et al. 2006 conducted a study on 599 dyspneic patients in the Emergency Department setting to determine if race or gender could influence the usefulness of NT-ProBNP levels. “In subjects with HF, there was no difference in median NT-proBNP concentrations between African American and non–African American (6196 versus 3597 pg/mL, P = 0.37). In subjects without HF, unadjusted NT-proBNP levels were lower in African American subjects than in non–African American subjects (68 versus 148 pg/mL, P < 0.03); however, when adjusted for factors known to influence NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial fibrillation, and body mass index), race no longer significantly affected NT-proBNP concentrations. There was no statistical difference in median NT-proBNP concentrations between male and female subjects with (4686 versus 3622 pg/mL, P = 0.53) or without HF (116 pg/mL versus 150 pg/mL, P = 0.62). Thus, NT-proBNP is useful for the diagnosis of exclusion of acute HF in dyspneic subjects, irrespective of race or gender”.15

BNP measurements must be analyzed in conjunction with standard diagnostic tests, medical history, and clinical findings. Clinicians should be aware that certain conditions, such as ischemia, infarction, renal dysfunction, age, atrial fibrillation, inflammation, myocarditis, hyperthyroidism, use of sacubitril/valsartan, and macro-proBNPemia overestimate BNP value, whereas the presence of obesity in the setting immediately after acute coronary syndrome onset, and pericardial effusions underestimate BNP value.12

Analysis of Evidence

The literature identifies that the natriuretic peptides B-type NP and NT-proBNP are most often used for the diagnosis of HF. In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor neprilysin inhibitors (ARNIs) (sacubitril/valsartan), the use of natriuretic peptides has grown in importance.

The literature and society guidelines do not give conclusive evidence as to the clinical use of BNP or NT-proBNP to alter treatments for patients with HF based on monitoring of blood levels. The use of other biomarkers such as ANP, high sensitivity Troponin, or soluble suppressor of tumorigenicity 2 (ST2) may when combined with BNP and NT-proBNP help assess Chronic HF.16 Therefore, the utility of BNP and NT-proBNP to monitor cardiac reverse remodeling is still ongoing and is not a covered service.

Bibliography

• Koratala A, Kazory A. Natriuretic peptides as biomarkers for congestive states: The cardiorenal divergence. Dis Markers. 2017:1454986.

• Hall C. Essential biochemistry and physiology of (NT-pro) BNP. Eur J Heart Fail. 2004;6(3):257-260.

• Cao Z, Jia Y, Zhu B. BNP and NT-proBNP as diagnostic biomarkers for cardiac dysfunction in both clinical and forensic medicine. Int J Mol Sci. 2019;20(8):1820.

• Savarese G., Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017;3(1):7–11.

• Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics-2017 update: A report from the American heart association. 2017;135(10):e146–e603.

• Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. 2022;145(18):e895-e1032.

• McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.

• Christ M, Mueller C. Use of natriuretic peptide assay in dyspnea. Dtsch Arztebl Int. 2008;105(6):95-100.

• Kelly R, Struthers AD. Are natriuretic peptides clinically useful as markers of heart failure? Ann Clin Biochem.2001;38(Pt 5):575-83.

• Mayo DD, Colletti JE, Kuo DC. Brain natriuretic peptide (BNP) testing in the emergency department. J Emerg Med.2006;31(2):201-10.

• Battaglia M, Pewsner D, Jüni P, Egger M, Bucher HC, Bachmann LM. Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: Systematic review of test accuracy studies. Arch Intern Med. 2006;166(10):1073-1080.

• Nishikimi T, Nakagawa Y. Potential pitfalls when interpreting plasma BNP levels in heart failure practice. J Cardiol. 202178(4):269-274.

• Tsutsui H, Ide T, Ito H, et al. JCS/JHFS 2021 guideline focused update on diagnosis and treatment of acute and chronic heart failure. J Card Fail. 2021;27(12):1404-1444.

• Tsutsui H, Albert N, et al. Natriuretic peptides: Role in the diagnosis and management of heart failure: A scientific statement from the heart failure association of the European society of cardiology, heart failure society of America and Japanese heart failure society. J Card Fail. 2023;29(5):787-804.

• Krauser D, Chen A, et al. Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: A ProBNP investigation of dyspnea in the emergency department (PRIDE) substudy. J Card Fail. 2006;12(6):452-457.

• Murphy SP, Prescott MF, Maisel AS, et al. Association between angiotensin receptor-neprilysin inhibition, cardiovascular biomarkers and cardiac remodeling in heart failure with reduced ejection fraction. Circ Heart Fail. 2021;14(6):653-662.

• Redfield MM, Rodeheffer RJ, Jacobsen SJ, et al. Plasma brain natriuretic peptide concentration: Impact of age and gender. J Am Coll Cardiol. 2002;40(5):976-82.