ModifiedPremera BluecrossPolicy N/A

Cardiac biomarkers (troponin, CK‑MB, BNP/NT‑proBNP, ST2, and others)

Defines Premera's coverage and reimbursement stance for laboratory measurement of cardiac biomarkers for diagnosis and prognosis of myocardial infarction and heart failure in acute and outpatient settings; applies to clinicians and labs submitting claims to Premera.

Policy Summary

PayerPremera Bluecross

PolicyCardiac biomarkers (troponin, CK‑MB, BNP/NT‑proBNP, ST2, and others)

Policy CodePolicy N/A

Change TypeMaterial changes to coverage (added BNP/NT‑proBNP reimbursable indicationsrestricted other biomarkers)

Effective DateFeb 6, 2026

Next Review DateN/A

Key ActionDocument BNP/NT‑proBNP indication (dyspnea or chronic HF severity) in clinical records to support reimbursement and limit outpatient BNP testing to four times per year.

SourceLink

POLICY UPDATE CHANGES

Measurement of B-type natriuretic peptide (BNP) or N-terminal pro BNP is considered reimbursable for diagnosing heart failure in individuals with dyspnea or for assessing severity in chronic heart failure (up to four times per year in the outpatient setting).

All other listed cardiac biomarkers, qualitative troponin testing, ST2 analysis, and any unlisted cardiac biomarkers for myocardial infarction diagnosis or prognosis are not reimbursable due to insufficient evidence of clinical benefit.

Policy added to Routine Test Management Policy section as a guide for clinical appropriateness and reimbursement methodology for lab tests.

up to 4/yrBNP outpatient frequency

Not reimbursableQualitative troponin

Not reimbursable

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Non‑BNP MI markers

82550–84588, 83006CPT codes listed

99th percentileTroponin threshold

2026-02-06Policy effective

Coverage Criteria for Cardiac Biomarkers

Biomarkers not reimbursable for ACS

ALL of the following

For individuals presenting with signs and symptoms of acute coronary syndrome, the following cardiac biomarkers for diagnosis and/or prognosis of myocardial infarction are not reimbursable:
List
- Aspartate aminotransferase (AST/SGOT)
- Cardiac creatine kinase isoenzyme MB (CK‑MB)
- Creatine kinase (CK)
- Creatine kinase isoenzymes
- Lactate dehydrogenase (LD, LDH)
- Myoglobin
- Copeptin
- Troponin C
- Heart‑type fatty acid binding protein (H‑FABP)
- Any other cardiac biomarkers not listed above

Outpatient testing — restricted / not reimbursable

ALL of the following

Cardiac biomarker testing performed in outpatient settings that are not capable of performing an adequate clinical MI evaluation (for example, independent laboratories or physician offices without appropriate clinical evaluation and observation capabilities) is not reimbursable for individuals presenting with signs and symptoms of acute coronary syndrome.
Qualitative measurement of cardiac troponin (troponin T or I) in the outpatient setting is not reimbursable.
Analysis of ST2 and/or its isoforms (e.g., Presage ST2) in the outpatient setting is not reimbursable.
Other novel biomarkers (e.g., copeptin, H‑FABP) used alone in the outpatient evaluation of suspected MI are not supported for reimbursement due to insufficient evidence of clinical benefit; these tests may be considered investigational or adjunctive and are not a substitute for high‑sensitivity troponin assays in appropriate clinical settings.

Coding and Diagnostic Thresholds

Referenced CPT codesCPT

82550	Creatine kinase (CK), (CPK); total
82552	Creatine kinase (CK), (CPK); isoenzymes
82553	Creatine kinase (CK), (CPK); MB fraction only
82554	Creatine kinase (CK), (CPK); isoforms
82725	Fatty acids, nonesterified
83006	Growth stimulation expressed gene 2 (ST2, Interleukin 1 receptor like-1)
83625	Lactate dehydrogenase (LD), (LDH); isoenzymes, separation and quantitation
83874	Myoglobin
83880	Natriuretic peptide
84450	Transferase; aspartate amino (AST) (SGOT)

1–10 of 12

1/2

Assays referenced (no procedure codes provided)mixed

not specified

Document lists named high-sensitivity troponin assays (e.g., Access HS-cTnI; ADVIA Centaur HS-cTnI; Alinity HS-cTnI; ARCHITECT STAT HS-cTnI; Atellica IM HS-cTnI; Dimension Vista HS-cTnI; Dimension EXL HS-cTnI; Elecsys HS-cTnT; VIDAS HS-cTnI; VITROS HS-cTnI) rather than billing codes; laboratories may also use validated laboratory-developed tests (LDTs) per CLIA

inv-26: TriageTrue troponin I rule-out/rule-in thresholds

TriageTrue rule-out thresholdTroponin I < 3 ng/L classified as rule-out (low risk of MI)

TriageTrue rule-in thresholdTroponin I > 60 ng/L classified as rule-in (diagnostic for MI in study cohort)

Clinical performancePOC hs-cTnI TriageTrue assay demonstrated high diagnostic accuracy comparable to central lab hs assays in Boeddinghaus et al.

inv-27: Troponin diagnostic threshold — 99th percentile of URL

Diagnostic criterionMyocardial infarction designated when a rising/falling pattern of cardiac troponin is present with at least one measurement > 99th percentile of the upper reference limit (URL)

Assay specificity

Provider Actions, Documentation, and Denial Risks

Prior Authorization

Prior Authorization — Not Specified

Prior authorization: No prior authorization requirement is specified for proprietary assays (e.g., Presage ST2) or for other cardiac biomarker tests in this policy.

Prior authorization not specified for proprietary assays (Presage ST2 and other vendor/platform tests).
Policy text and references do not state any prior authorization requirement.

Documentation Required

Documentation Requirements

Documentation: For BNP/NT-proBNP testing, document indication such as signs/symptoms of heart failure (e.g., dyspnea) or intent to establish disease severity in chronic HF. For MI evaluation, document symptom timing, serial troponin sampling, assay used, and values relative to the assay-specific 99th percentile URL.

Document clinical indication for BNP/NT-proBNP (e.g., dyspnea to diagnose/exclude HF; intent to assess chronic HF severity).

Background and Evidence Summary

BACKGROUND: Cardiac biomarkers are molecules released into blood after myocardial injury. Historically, enzymes such as AST, CK, CK‑MB, LDH and proteins like myoglobin were used for MI diagnosis, but many of these lack the cardiac specificity of troponins. Cardiac‑specific troponins (cTnI and cTnT), particularly when measured with high‑sensitivity assays, are now the recommended primary biomarkers for diagnosing myocardial infarction. BNP and NT‑proBNP are established biomarkers for diagnosing heart failure and assessing severity in patients presenting with dyspnea.

The policy cites guideline and primary literature references that informed the background and coverage statements; the list of references is provided for readers seeking source material and further detail.

Definitions and Key Terms

inv-57: BNP / NT-proBNP definitions

BNP definitionB-type (brain) natriuretic peptide released mainly from left ventricle; marker of volume/pressure overload used to diagnose heart failure

NT-proBNP definitionN-terminal pro-BNP is the amino-terminal fragment from proBNP cleavage; measured as a natriuretic peptide biomarker for HF diagnosis and prognosis

Equivalence noteNT-proBNP >900 pg/mL roughly equivalent to BNP >100 pg/mL

inv-58: Cardiac troponin (cTnI, cTnT)

Cardiac troponin isoformsCardiac-specific troponin I (cTnI) and troponin T (cTnT) have high specificity for cardiac tissue and are the primary biomarkers recommended for MI diagnosis

Troponin C not usedTroponin C (TnC) is not used as a cardiac biomarker

Policy Revision History

2025-10-14policy_approval

New policy approved establishing reimbursability of BNP/NT-proBNP for diagnosing heart failure or assessing chronic heart failure severity and stating non-reimbursability of qualitative troponin, ST2, and other listed/unlisted cardiac biomarkers for MI diagnosis/prognosis due to insufficient evidence.

2026-02-06policy_effective_dateLatest

Policy effective for dates of service on or after this date following 90-day provider notification.

Policy Summary

PayerPremera Bluecross

PolicyCardiac biomarkers (troponin, CK‑MB, BNP/NT‑proBNP, ST2, and others)

Policy CodePolicy N/A

Change TypeMaterial changes to coverage (added BNP/NT‑proBNP reimbursable indicationsrestricted other biomarkers)

Effective DateFeb 6, 2026

Next Review DateN/A

Key ActionDocument BNP/NT‑proBNP indication (dyspnea or chronic HF severity) in clinical records to support reimbursement and limit outpatient BNP testing to four times per year.

SourceLink

On This Page

99th percentile is assay-specific and used as the decision level for MI diagnosis

Alternative when cTn unavailableCK‑MB above the 99th percentile of the URL is an alternative decision level if cTn is not available

inv-28: sST2 prognostic cutoffs

sST2 prognostic rangeStudies report prognostic thresholds generally in the ~30–44 ng/mL range associated with increased risk

Specific study cutoffsHou et al. identified a best cutoff for all-cause mortality at ~43.43 ng/mL (AUC 0.72); other reports note thresholds such as ≥30 ng/mL and >36.3 ng/mL in higher-risk tertiles

Assay example and rangePresage ST2 assay measuring range reported 3.1–200 ng/mL (FDA clearance), used as a prognostic adjunct in chronic HF

inv-29: NT‑proBNP/BNP rough equivalence

Rough equivalenceNT-proBNP > 900 pg/mL is roughly equivalent to BNP > 100 pg/mL

Clinical useNatriuretic peptides should be interpreted within the full clinical evaluation for dyspnea and heart failure diagnosis

SettingsBNP/NT-proBNP useful for diagnosis, prognosis, predischarge assessment, and chronic HF monitoring

inv-30: TriageTrue triage cutoffs (hs‑cTnI POC)

Triage cutoffs (POC hs-cTnI)Rule-out < 3 ng/L; Rule-in > 60 ng/L per the TriageTrue hs-cTnI study algorithm

One-hour triageTriageTrue algorithm allowed a triage decision after one hour in a substantial proportion of patients in the study

Comparative performanceTriageTrue POC hs-cTnI performance was at least comparable to validated central laboratory hs assays

inv-31: troponin sampling interval

Recommended sampling intervalObtain initial troponin at presentation and repeat per assay-specific interval (commonly 30 minutes to 3 hours); interpret using 99th percentile or limits of detection

Serial testing for rise/fallMeasure troponin at presentation and again 3–6 hours after symptom onset to identify rise/fall pattern for MI diagnosis when indicated

If onset ambiguousUse time of presentation as time zero for sampling when symptom onset is unclear; obtain additional samples >6 hours if ECG changes or intermediate/high risk

inv-32: SCAI periprocedural biomarker multiples

SCAI CK‑MB criterion (normal baseline)Peak CK‑MB within 48 hours > 10× local laboratory ULN, or >5× ULN with new pathologic Q‑waves or new persistent LBBB

SCAI cTn criterion (normal baseline)If CK‑MB unavailable and baseline normal, cTn (I or T) within 48 hours > 70× ULN, or >35× ULN with new pathologic Q‑waves or new persistent LBBB

Adjusted rulesWhen baseline biomarkers are elevated, require absolute increments from preprocedure level equal to the multiples above, with additional clinical criteria if biomarkers are not stable/falling

inv-33: BNP/NT-proBNP frequency — up to four times/year

Allowed outpatient frequencyBNP/NT-proBNP reimbursable up to four times per year in the outpatient setting for chronic heart failure assessment

Clinical indicationUse for diagnosis/exclusion of HF in dyspnea and for assessing chronic HF severity; interpret within full clinical context

Serial measurementsSerial BNP/NT-proBNP may provide prognostic information and can be used predischarge or for chronic HF management, but serial-guided therapy lacks consistent evidence for improving outcomes

Document symptom onset time and timing of troponin draws when evaluating for MI (initial and repeat samples per guideline-recommended intervals).

Document assay type (high-sensitivity vs contemporary), sampling times, and biomarker values relative to assay-specific 99th percentile URL for MI diagnosis.

Denial Risk

Denial Risk — Not Reimbursable Tests

Denial risks: Several tests are identified as not reimbursable and present a high denial risk if billed for outpatient MI evaluation or routine outpatient use.

Legacy MI biomarkers not reimbursable: AST (SGOT), CK, CK-MB, CK isoenzymes, LD/LDH, myoglobin.
Outpatient qualitative troponin (troponin T or I, qualitative) is not reimbursable.
ST2 testing (including Presage) is not reimbursable in the outpatient setting.
Any other listed or unlisted non‑troponin cardiac biomarkers for MI diagnosis/prognosis are not reimbursable.

Documentation Required

Troponin Serial Testing Expectations and Timing-Related Denial Risk

Troponin serial testing expectations and assay-related timing: Use high-sensitivity cTn assays when available. Measure troponin at presentation and repeat per guideline timing (e.g., 3–6 hours after symptom onset or per assay-specific protocols; if symptom onset unclear, use time of presentation). Assay choice and sampling timing affect interpretation; non‑hs assays or improper timing may lead to denial or clinical nonconcordance with policy.

Expect initial and repeat troponin sampling in suspected ACS (presentation and repeat per 3–6 hour window or assay-specific algorithms).
If symptom onset is ambiguous, use time of presentation as time zero for sampling.
High-sensitivity assays are recommended; use assay-specific thresholds (99th percentile or LOD as recommended).
Non‑high-sensitivity troponin use or incorrect sampling intervals may lead to denial or require additional documentation.

Step Therapy

Step Therapy — Not Applicable

Step therapy / quantity limits: Not applicable — this policy does not specify any step therapy requirements or quantity-limit rules for cardiac biomarker testing.

No step-therapy requirements are described in this policy for biomarker testing.

Note

References — Guideline-Based Expectations

References and guideline support: National and international guidelines inform the documentation and testing expectations above (e.g., ESC/ACC/AHA/WHF Fourth Universal Definition of MI, AHA/ACC NSTE-ACS guidance, ACC/AHA/HFSA heart failure guidelines, NICE recommendations, and ASCP statements).

Guideline citations that inform documentation and testing: Fourth Universal Definition of MI (2018), AHA/ACC NSTE-ACS (2014), ACC/AHA/HFSA heart failure guidelines (2017, 2022), NICE guidance on troponin and HF, and ASCP guidance on not using CK‑MB or myoglobin.

Assay dependenceDiagnostic use relies on assay-specific thresholds such as the 99th percentile of the URL

inv-59: Acute myocardial infarction (per 2018 Universal Definition)

UDMI criterion for AMIAcute myocardial infarction requires a rising/falling pattern of cardiac troponin with at least one value above the 99th percentile of the assay URL

High-sensitivity assaysHigh-sensitivity cTn assays are recommended for routine clinical use in MI evaluation

CK‑MB alternativeCK‑MB above 99th percentile may be used as decision level if cTn not available

inv-60: sST2 (soluble ST2)

sST2 definitionSoluble ST2 (sST2) is the circulating isoform of ST2, an interleukin-1 receptor family member implicated in cardiomyocyte stress, fibrosis, and adverse remodeling

Clinical rolesST2 is measured (eg, Presage assay) as a prognostic biomarker in chronic heart failure when used with clinical evaluation and natriuretic peptides

Presage assay FDA clearancePresage ST2 assay approved by FDA (2011) and reports measuring range approximately 3.1–200 ng/mL

inv-61: 99th percentile threshold

99th percentile meaningThe 99th percentile of the assay's upper reference limit (URL) is the assay-specific cutoff used to define an abnormal troponin value for MI diagnosis

Assay-specific useUse sex-specific or assay-specified 99th percentiles where applicable; threshold selection depends on the assay and guideline recommendations

NICE guidance on threshold useNICE recommends using thresholds at or near the limit of detection or the 99th percentile depending on assay for early rule-out strategies

inv-62: clinically relevant periprocedural MI (SCAI definition)

Definition of clinically relevant periprocedural MISCAI defines clinically relevant MI after revascularization by biomarker multiples and clinical findings (eg, CK‑MB >10× ULN or >5× ULN with new Q‑waves; or cTn >70× ULN or >35× ULN with Q‑waves) within 48 hours

Contextual criteriaWhen baseline biomarkers are elevated, require absolute increments from the most recent preprocedure level; additional clinical signs (new ECG changes, heart failure, hypotension) are considered

Preferred markerSCAI expresses preference for CK‑MB but includes cTn if CK‑MB unavailable

inv-63: high-sensitivity troponin

High-sensitivity troponin definitionHigh-sensitivity troponin (hs-cTn) assays have improved analytic sensitivity enabling early diagnosis and rule-out strategies in suspected MI

Recommended useGuidelines (ESC, NICE) recommend hs-cTn for routine evaluation and early rule-out, with assay-specific sampling intervals

POC hs-cTn examplePOC hs-cTn assays (eg, TriageTrue) have been evaluated and can provide rapid triage decisions when performance comparable to central lab assays

inv-64: ST2

ST2 termST2 refers to the interleukin-1 receptor-like 1 protein with soluble (sST2) and transmembrane (ST2L) isoforms; sST2 is measured for prognostic information in HF

Biologic rolesST2 can bind IL-33 and block cardioprotective IL-33/ST2L signaling, promoting hypertrophy and fibrosis experimentally

Clinical assaysPresage is a proprietary sST2 assay cleared by FDA for prognostic use in chronic HF

inv-65: BNP/NT-proBNP (short restatement)

BNP/NT-proBNP summaryBNP and NT-proBNP are natriuretic peptide biomarkers used to diagnose and assess severity of heart failure; interpret within complete clinical evaluation

Clinical applicationsUseful in acute dyspnea workup to establish or exclude HF; also used for prognosis in chronic or acutely decompensated HF and predischarge assessment

Outpatient frequencyPolicy allows outpatient BNP/NT-proBNP testing up to four times per year for chronic HF assessment