Response to Comments: B-type Natriuretic Peptide (BNP) Testing

Palmetto GBA (Palmetto) has solicited comments from interested parties to the proposed changes to B-type Natriuretic Peptide (BNP) Testing DL34410. We, as a manufacturer of a BNP test, have prepared a response to the proposed LCD. We recognize that comments are being accepted regarding the consolidation of Part A and Part B services. It is our position that the following comments are regarding the consolidation of Part A and Part B as the 2 LCDs differ in the coverage of BNP testing.

We are opposed to the proposed following language, “There is no conclusive evidence currently to warrant the use of BNP or NT-proBNP to alter or monitor treatment of HF. Therefore, BNP measurements for monitoring and management of CHF are not a covered service.” We respectfully request a review and consideration of the following and suggest that the following language be used in the proposed LCD:

“Palmetto considers measurement of plasma brain natriuretic peptide (BNP) medically necessary for the following indications:

1. To differentiate dyspnea due to heart failure from pulmonary disease; or
2. To determine prognosis or disease severity in chronic heart failure; or
3. To screen for heart failure in adults with diabetes mellitus; or
4. Measurement upon hospital admission to determine prognosis in persons with acutely decompensated heart failure.”

1. Universal Definition and Classification of Heart Failure:

In recognition of the importance of biomarkers to support the detection of cardiac dysfunction at an early stage, the definition of stage B in the recent Universal Definition and Classification of Heart Failure was revised to include asymptomatic individuals with at least one of the following: 1) evidence of structural heart disease, 2) abnormal cardiac function, or 3) elevated natriuretic peptide levels or elevated cardiac troponin levels.

2. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure:

In patients at risk of developing HF, BNP or NT–proBNP–based evaluations followed by team-based care, including a cardiovascular specialist, can be useful to prevent the development of LV dysfunction or new-onset HF.

Patients in which guideline-directed medical therapy (GDMT) leads to a reduction in BNP and NT-proBNP levels represent a population with improved long-term outcomes compared with those with persistently elevated levels despite appropriate treatment. BNP and NT-proBNP levels and their change could help guide discussions on prognosis as well as adherence to, and optimization of, GDMT.

3. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Based upon the results of STRONG-HF, high-intensity care for initiation and rapid up-titration of oral HF therapies and close follow-up in the first 6 weeks after discharge for an acute HF hospitalization is recommended to reduce HF readmission or all-cause death. During the follow-up visits, particular attention should be paid to symptoms and signs of congestion, blood pressure, heart rate, NT-proBNP values, potassium concentrations, and eGFR.

4. Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction

“Despite clinical policy documents recommending serial measurement of NT-proBNP at approximately 3- to 6-month intervals in stable chronic HFrEF, there exists a relative paucity of data supporting such a recommendation. The results from this study affirm this recommendation, suggesting that NT-proBNP measurements every 3 months during HF therapy increases discrimination for events compared to less frequent measurement. More recent measurements add significantly to prior values, even if the prior concentrations were either low or elevated. Another important finding of this analysis is that the onset of NT-proBNP rise may occur well ahead of clinical events, providing a window of opportunity to intervene.”

5. Serial NT-proBNP Measurements and Implementation of Guideline-Directed Medical Therapy

In this letter to the editor, the authors expand upon the publication from Fuery et al on the Prognostic Impact of Repeated NT-proBNP Measurements in Patients with Heart Failure with Reduced Ejection Fraction. NTproBNP may potentially serve as our “virtual physical examination” and, in conjunction with assessment of symptoms and other laboratory results, give clinicians more confidence to initiate and titrate medications virtually and improve health system bandwidth to rapidly optimize outpatient GDMT. A stable high/rising NT-proBNP in response to maximally tolerated quadruple therapy may signal the need for clinician action that may not have otherwise occurred with clinical assessment alone. Potential actions that could be considered as indicated in such a scenario include prioritizing an in-person clinical assessment, moving up the next clinic appointment, escalating diuretics, repeating cardiac imaging, considering adjunctive drugs or devices, and referral for advanced HF therapies. In contrast, a flat/declining NT-proBNP in response to therapy should give clinicians confidence that these additional steps are likely not needed or are of lower value.

6. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial

The 2022 STRONG-HF multinational, multicenter trial showed using NT-proBNP as a part of an up-titration protocol resulted in measurably improved outcomes across several domains over usual care: overall outcome (vital signs, clinical evaluations), quality of life, hospital readmission rates, and death rates. The high-intensity care arm involved four scheduled outpatient visits over the 2 months after discharge that closely monitored clinical status, laboratory values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. The study showcased a reduction in the relative risk of HF readmission and mortality by 34% as compared with usual care within 6 months.

7. Heart Failure, Saxagliptin and DM - observation from SAVOR-TIMI 53

Subjects at greatest risk of hospitalization for heart failure had previous heart failure, an estimated glomerular filtration rate ≤60 mL/min, or elevated baseline levels of N-terminal pro B-type natriuretic peptide.

8. Natriuretic Peptide-based screening and collaborative care for Heart Failure: The STOP-HF Randomized Trial

Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure.

9. Effects of Canagliflozin on Amino-Terminal Pro-B-type Natriuretic Peptide: Implications for Cardiovascular Risk Reduction

Elevated amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with HF diagnosis and predict cardiovascular risk. In adjusted models, baseline NT-proBNP ≥125 pg/ml was prognostic for incident HHF (hazard ratio [HR]: 5.40; 95% CI: 2.67 to 10.9), HHF/cardiovascular death (HR: 3.52; 95% CI:

2.38 to 5.20), and all-cause death (HR: 2.53; 95% CI: 1.78 to 3.61). Mediation analyses suggested that 10.4% of the effects of canagliflozin on HHF were reflected in NT-proBNP lowering.

10. Association Between Angiotensin Receptor–Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction

Reduction in NT-proBNP and hs-cTnT following initiation of sacubitril/valsartan may be a helpful indicator of reverse cardiac remodeling in the absence of repeat imaging shortly after initiating treatment with sacubitril/valsartan, which may be a reassurance regarding lack of need for more intensive imaging. Similarly, lack of reductions in these biomarkers may help identify patients in whom intensification of guideline-directed therapies or closer follow-up are warranted.

Additionally, the proposed policy does not take into consideration the use of NT-proBNP testing in the Diabetic population. We request that consideration is given to include the diabetic use case as warranted by the following evidence:

11. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025:

Adults with diabetes are at increased risk for the development of asymptomatic cardiac structural or functional abnormalities (stage B heart failure) or symptomatic (stage C) heart failure. Consider evaluating adults with diabetes by measuring a natriuretic peptide (B-type natriuretic peptide [BNP] or N-terminal pro-BNP [NTproBNP]) to facilitate prevention of stage C heart failure.

Additionally, in asymptomatic individuals with diabetes and abnormal natriuretic peptide levels, echocardiography is recommended to identify stage B heart failure.

12. American Diabetes Association 2022 Consensus Statement:

Detection of people at high risk for HF (stage A) or those with stage B HF (without symptoms but with either structural/functional cardiac abnormalities or elevated biomarkers natriuretic peptides or troponin) would permit earlier implementation of effective strategies to prevent or delay the progression to advanced HF in individuals with diabetes, such as optimizing use of RAAS inhibitors and β-blockers or earlier initiation of other therapies with more recently proven ability to prevent progression of HF such as sodium glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i).

The addition of relatively inexpensive biomarker testing as part of the standard of care may help to refine HF risk prediction in individuals with diabetes.

13. 2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure with Reduced Ejection Fraction:

Current clinical practice guidelines give a Class I recommendation to measure BNP or NT-proBNP to support a clinical diagnosis of HF, assess disease severity, or establish prognosis.

Trends in natriuretic peptide concentrations inform prognosis as well as the potential presence and severity of congestion and trajectory of left ventricular remodeling, and they also closely track with health status. Thus, a measurement of BNP or NT-proBNP at each clinical evaluation may inform clinical decisions (e.g., diuretic agent dosing and other GDMT adjustments); more frequent measurement might be appropriate in certain circumstances, such as during rapid medication titration or in the setting of symptom instability.

In the setting of worsening symptoms, reassessment of BNP or NT-proBNP may be informative. Therefore, measurement of BNP or NT-proBNP is useful to monitor risk, assist in decision making regarding the ordering of imaging studies to evaluate LV remodeling, and to provide helpful objective data regarding decision-making for referral to an advanced HF specialist.

14. Biomarkers for the Diagnosis of Heart Failure in People with Diabetes: A Consensus Report from Diabetes Technology Society (2023)

Biomarker screening for HF in PWD is a sensible public health practice because both the disease and the available screening tests meet the criteria of a sound screening program for identifying asymptomatic HF.

DTS consensus recommendations for routine biomarker screening for HF in PWD with Stage A HF:

*Table was provided for reference.

15. Serial Measurement of Natriuretic Peptides and Cardiovascular Outcomes in Patients With Type 2 Diabetes in the EXAMINE Trial

After adjusting for potential confounders, NT-proBNP at baseline was independently associated with the development of major CV events, in particular hospitalization for HF. Patients who had persistently high

NT-proBNP (P < 0.001) or developed high NT-proBNP at 6 months (P < 0.001) were at a significantly higher risk for CV death/HF than those in whom NT-proBNP remained low at both time points or who had a high NT-proBNP value at baseline that subsequently declined to the low category. Absolute changes in NT-proBNP by 6 months were also strongly associated with subsequent outcomes.

16. Optimal Screening for Predicting and Preventing the Risk of Heart Failure Among Adults with Diabetes without Atherosclerotic Cardiovascular Disease: A Pooled Cohort Analysis

Among adults with diabetes and no prevalent atherosclerotic cardiovascular disease, the 5-year number needed to treat to prevent 1 heart failure (HF) event using an SGLT2i (sodium-glucose cotransporter 2 inhibitor) in those identified as high risk with a risk score, cardiac biomarkers, or echocardiography was comparable with those with diabetes and prevalent atherosclerotic cardiovascular disease.

Sequential use of a risk score followed by natriuretic peptide testing among those deemed low risk by the risk score identified 84% of incident HF events and had a low 5-year number needed to screen, the fewest tests, and the lowest screening cost to prevent 1 HF event among 2-step screening strategies.

17. Increases in NP precede Heart Failure Hospitalization in Patients with a recent Coronary Event and Type 2 Diabetes Mellitus

“The estimated rates of monthly increase in NP levels were 1% to 2% from 12 to 6 months before HFH, increasing to ≈8% and 11% per month over the final 6 months for BNP and NT-proBNP, respectively. Increases in NP were also evident preceding other outcomes examined (death, cardiovascular death, myocardial infarction, stroke), but the magnitude of increase was notably less than for HFH. The overall increase in NP among patients experiencing HFH during follow-up was most prominent among patients without a history of HF. Patients without a history of HF had an increase (≈3- to 4-fold) in NP preceding HFH that was greater than that in patients with a history of HF at randomization (≈50% increase; P for interaction=0.029 for BNP and 0.067 for NT-proBNP).”

Based upon the evidence above, many Payers have deemed NT-proBNP testing as Medically Necessary, including Cigna, effective May 2024. The Cigna Policy supporting the use of NT-proBNP is attached to this letter as well as PDFs of each publication referenced, organized by bullet number.

We appreciate your consideration of this request and are optimistic that Palmetto will adopt the language we proposed for the revised LCD. Thank you for your consideration.

*References were provided for review.

Thank you for your comment. We have clarified our indication based on review of the evidence provided and review of additional sources. We have modified the criteria to reflect the use of frequent or serial levels due to their lack of conclusive evidence. Guidelines from the American College of Cardiology and American Heart Association recommend the measurement of BNP and NT-proBNP to assess risk and prognosis in patients with known heart failure. The frequent and repeated use of BNP and NT-proBNP is not indicated as plasma levels can vary with the assay used and there is no simple conversion factor to compare BNP and NT-proBNP levels which should not be ordered together.

We are pleased to provide comments on Proposed LCD - B-type Natriuretic Peptide (BNP) Testing (DL34410). We appreciate the opportunity to contribute to the review process and commend CMS for its efforts to ensure appropriate and effective use of BNP testing.

Our purpose is to enable healthcare providers to increase value by empowering them on their journey towards expanding precision medicine, transforming care delivery, and improving patient experience, all enabled by digitalizing healthcare. An estimated five million patients globally everyday benefit from our innovative technologies and services in the areas of diagnostic and therapeutic imaging, radiation oncology, laboratory diagnostics and molecular medicine, as well as digital health and enterprise services. We are a leading medical technology company with over 120 years of experience and 18,500 patents globally. With over 66,000 dedicated colleagues in over 70 countries, we will continue to innovate and shape the future of healthcare.

We thank Palmetto in advance for reviewing our recommendations to this LCD. LCDs provide beneficiary access to lifesaving and medically necessary products and procedures. When followed, the local coverage process results in coverage decisions on items and services that benefit Medicare beneficiaries through an open and participative decision-making process.

We are concerned that the proposed Local Coverage Determination (LCD) DL34410 restricts Medicare coverage for B-type Natriuretic Peptide (BNP) and NT-proBNP testing when used to monitor or alter heart failure (HF) treatment, citing insufficient conclusive evidence. While evidence for routine therapy titration remains limited, emerging research highlights a critical role for these biomarkers in identifying high-risk patients, guiding clinical decisions, and supporting cost-effective care. Restricting coverage risks exacerbating hospital readmissions and increasing Medicare expenditures.

BNP and NT-proBNP as Essential Monitoring Tools

BNP and NT-proBNP reflect myocardial stress and treatment response in HF. The PIONEER-HF trial demonstrated that sacubitril/valsartan—an angiotensin receptor-neprilysin inhibitor (ARNI) that enhances natriuretic peptide effects—significantly reduced NT-proBNP levels within weeks in acute HF patients. This reduction correlated with fewer rehospitalizations, highlighting the biomarkers’ role in post-discharge monitoring. Tsutsui et al. (2021) in the JCS/JHFS Guidelines also recommend BNP/NT-proBNP to assess ongoing HF management beyond initial diagnosis, reinforcing their clinical value.

Identifying High-Risk Patients to Improve Outcomes

Serial BNP/NT-proBNP measurements help identify high-risk patients requiring intensified care, even if broad therapy adjustments based solely on BNP levels have not yet been universally validated. A 2023 joint scientific statement from the Heart Failure Association and others noted that while PRIMA II did not show improved outcomes with strict NT-proBNP-guided therapy, failure to achieve a >30% reduction in BNP was linked to significantly increased mortality risk. Identifying these nonresponders allows for targeted interventions, potentially reducing avoidable hospital admissions and healthcare costs.

Economic and Healthcare Implications

Denying coverage for BNP and NT-proBNP testing may increase Medicare expenditures by limiting access to a cost-effective tool for HF management. Studies indicate that elevated BNP/NT-proBNP levels correlate with increased hospitalization risk, and their use in monitoring enables early identification of patients at risk of decompensation. The Cao et al. (2019) study emphasized BNP/NT-proBNP as essential monitoring biomarkers, while PIONEER-HF findings further support their role in tracking treatment efficacy.

By maintaining reimbursement, Medicare can support real-world data collection, refine the role of BNP/NT- proBNP testing in HF management, and promote proactive risk stratification strategies that improve patient outcomes and reduce unnecessary healthcare costs.

We appreciate this opportunity to share our recommendations for your consideration. Incorporating the recommendations in this letter is in the best interest of patients and will ensure continued and appropriate access to diagnostic services for Medicare beneficiaries.

Thank you for your comment. We are not denying the use of BNP or for that matter NT-proBNP as its use is well documented in the heart failure population. We are simply providing a guideline for its proper utilization in the Medicare Beneficiary population based on current evidence and standards of practice from national and international societies. Your comments and literature document that the use of BNP and NT-proBNP for routine therapy titration is limited and not universally supported. However, should the literature conclusively change the standards of care a reconsideration will be warranted.

We are pleased to submit the following comments to Palmetto in response to the proposed Local Coverage Determination (LCD): B-type Natriuretic Peptide (BNP) Testing and accompanying billing and coding article (DL34410 and DA56605).

Functioning as an association within another company, we are the only multi-faceted, policy organization that deals exclusively with issues facing in vitro diagnostic companies in the United States and abroad. Our member companies produce advanced, in vitro diagnostic tests that facilitate evidence-based medicine, improve quality of patient care, enable early detection of disease and reduce overall health care costs. Our membership includes manufacturers engaged in the development of innovative diagnostic technologies supporting the advancement of public health, helping to deliver cutting-edge care to patients worldwide.

We thank Palmetto GBA in advance for reviewing our recommendations to this LCD. LCDs provide beneficiary access to lifesaving and medically necessary products and procedures. When followed, the local coverage process results in coverage decisions on items and services that benefit Medicare beneficiaries through an open and participative decision-making process.

The proposed LCD states that the existing Part A BNP Testing L34410 LCD is being taken out for comment to incorporate Part B services that were previously included in the BNP Level L33422 LCD. The existing Part B LCD, L33422 will be retired once the consolidated Part A and Part B LCD (DL34410) becomes effective. Palmetto GBA is accepting comments specific to the consolidation of Part A and Part B services.

We are concerned that as drafted the proposed policy will restrict access to BNP testing for patients and limit the availability of a valuable tool used by providers for lowering rates of adverse cardiovascular events and improving patient quality of life. The proposed LCD reads "There is no conclusive evidence currently to warrant the use of BNP or NT-proBNP to alter or monitor treatment of heart failure (HF). Therefore, BNP measurements for monitoring and management of congestive heart failure (CHF) are not a covered service." Historically the Part A policy, including the text above, has resulted in blocking access to NT-proBNP testing in the inpatient setting. The Part B policy has allowed for testing in the outpatient setting. The proposed policy states within its rationale for determination that there is not conclusive evidence as to the clinical use of BNP or NT-proBNP to alter treatments for patients with HF based monitoring of blood levels and that research into this clinical utility is still ongoing and therefore not a covered service.

Using BNP to guide care requires clinicians to interpret the test in accordance with the patient’s unique clinical situation and therapies. BNP and NT-proBNP (commonly referred to as natriuretic peptides (NPs)) are the gold standard in prognostic diagnosis and stratification of HF and their use is recommended by both ESC and ACC/AHA guidelines. Additionally, BNP- or NT-proBNP–guided HF management has been generally shown to result in superior medical management compared with standard care when correctly applied.

A summary of evidence for BNP-guided HF management is included in a 2013 review article which notes that in nearly every randomized control trial (RCT) examining the approach, whether positive for their primary end point or not, patients treated in the biomarker-guided arm tended to have more up titrations of therapies and more often finished the trial on higher doses of guideline-directed medical therapies compared with patients managed with standard clinical acumen alone. After reviewing several RCTs and other research, the article also concludes that “when correctly applied, biomarker-guided care results in lower rates of adverse cardiovascular events, better quality of life, and reverse ventricular remodeling and may be associated with reduced rates of death.” A more recent RCT GUIDE-IT, failed to show differences in BNP vs non-BNP guided treatment, however, this study has been criticized for having a fundamental flaws in its design, specifically, that the patients enrolled in GUIDE-IT were seen by doctors with deep knowledge of guideline directed medical therapy, meaning that the “usual care” arm may not be representative of the typical patient care access and frequency. Moreover, meta- analyses for several other trials, including many small RCTs, showed that a NP-guided treatment is associated with lower rates of all-cause mortality and HF hospitalization. Therefore, we believe current evidence is sufficient to continue existing coverage, and that finalizing this policy as written would have severe unintended consequences for patient with CHF. To ensure appropriate coverage is maintained, we recommend Palmetto GBA include BNP or NT-BNP to alter or monitor treatment of HF be maintained in the final policy.

We appreciate this opportunity to share our recommendations for your consideration. Incorporating the recommendations in this letter is in the best interest of patients and will ensure continued and appropriate access to diagnostic services for Medicare beneficiaries. Our members are committed to working with you.

*References were provided for review.

Thank you for your comment. Please see response # 2 and #3 above.

My physicians took issue with the proposal to not cover BNP or NTproBNP in asymptomatic HF patients.

Thank you for your comment. The use of BNP or NT-proBNP as a risk assessment in non-symptomatic patients is considered screening and is not a covered Medicare benefit. The use must be reasonable and necessary as cited in Title XVIII of the Social Security Act, 1862(A)(1)(a) and its rationale documented in the beneficiaries’ medical record. There are no guidelines or recommendations for routinely using BNP or NT-proBNP as there is limited predictive value for the prognosis or monitoring of the clinical status of critically ill patients.