CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Biomarkers for Myocardial Infarction and Chronic Heart Failure

Coverage and limitations for laboratory measurement of cardiac biomarkers (e.g., troponin, BNP/NT-proBNP, CK-MB, LDH, myoglobin, ST2) for diagnosis and prognosis of myocardial infarction and heart failure in outpatient settings for Blue Cross Blue Shield - Tennessee.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyBiomarkers for Myocardial Infarction and Chronic Heart Failure

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionDocument troponin timing and clinical context when requesting quantitative troponin testing up to four times within 72 hours for suspected MI.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

up to 4troponin quantitative tests allowed in first 72 hours

up to 4/yroutpatient NT-proBNP/BNP for chronic HF

multiplelisted biomarkers not covered

96%sites using troponin as primary biomarker

16CPT/HCPCS procedure codes listed

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Coverage criteria for cardiac biomarkers

inv-01: Covered indications

Covered when ALL of the following are met for the specified tests:

Quantitative troponin for suspected MI: Individual presents with signs and symptoms of acute coronary syndrome and testing is performed at an outpatient facility capable of performing an adequate clinical MI evaluationUp to 4 tests within first 72 hours

Quantitative troponin T or I only

BNP/NT-proBNP for heart failure: Individuals with dyspnea for diagnosis of heart failure OR individuals with chronic heart failure for establishing disease severityUp to 4 tests per year outpatient for chronic HF

BNP or NT-proBNP acceptable

inv-02: Not medically necessary / Not covered

Tests and uses that DO NOT meet coverage criteria:

Non-covered biomarkers for MI diagnosis/prognosis: Aspartate aminotransferase (AST), CK‑MB, CK, CK isoenzymes, LD/LDH, myoglobin, copeptin, troponin C, C‑reactive protein, H‑FABP, any other cardiac biomarkers not listed as coveredNone

Listed explicitly as not meeting coverage criteria

ST2 and isoforms: Analysis of ST2 and/or its isoforms (e.g., Presage ST2) in the outpatient settingNone

Does not meet coverage criteria due to lack of evidence

Setting restriction for troponin: Quantitative troponin performed in outpatient setting that is NOT capable of adequate clinical MI evaluation (e.g., independent laboratory or physician office)None

Does not meet coverage criteria

inv-03: Diagnostic and prognostic biomarker coverage

Covered when ALL of the following are met for respective clinical contexts

Acute MI diagnosis with troponin: Use cardiac troponin I or T (high-sensitivity assays recommended) measured at presentation and with serial sampling; designate acute MI when there is a rising and/or falling pattern with at least one value above the assay-specific 99th percentile upper reference limit (URL).>=99th percentile (assay-specific)

If troponin assay unavailable, CK‑MB above 99th percentile may be used as alternative

Troponin sampling timing: Measure troponin at presentation and approximately 3–6 hours after symptom onset; measure beyond 6 hours if initial serial exams are normal but clinical or ECG features suggest ACS; if symptom onset is ambiguous, use time of presentation as time zero.timing: presentation and 3–6 hours (or later if indicated)

AHA/ACC timing recommendations

Natriuretic peptide use in dyspnea/heart failure:

inv-04: Troponin testing for suspected ACS

Covered when ALL of the following are met

AHA/ACC troponin diagnostic criteria: Measure cardiac-specific troponin (I or T) at presentation and 3–6 hours after symptom onset in all patients with suspected ACS to identify a rising and/or falling pattern.timing: 0 and 3–6 h

If symptom onset ambiguous, use time of presentation as time zero

inv-05: Extended troponin testing

Covered when ANY of the following apply

Additional troponin beyond 6 hours: Obtain additional troponin levels beyond 6 hours in patients with initial normal serial troponins who have ECG changes and/or intermediate or high-risk clinical features.>6 h after presentation

Supports diagnosis when initial serial tests are non-diagnostic

inv-06: Troponin remeasurement in MI

Covered when ALL of the following are met

Troponin remeasurement on day 3–4: Remeasure troponin once on day 3 or 4 in patients with confirmed MI to estimate infarct size and dynamics of necrosis for prognostic assessment.day 3–4

Prognostic use; considered reasonable by AHA/ACC (level of evidence B)

inv-07: Natriuretic peptide testing in HF

Covered when ALL of the following are met

BNP/NT-proBNP diagnostic and prognostic use: Measure BNP or NT‑proBNP to support diagnosis or exclusion of heart failure in patients presenting with dyspnea and for prognosis/disease severity in chronic or acutely decompensated HF; predischarge levels may inform postdischarge prognosis.clinical context: dyspnea or HF hospitalization; up to 4 tests/year outpatient for chronic HF

ACC/AHA/HFSA provides Class I recommendations for diagnosis and prognosis

inv-08: Emerging biomarkers (sST2, galectin-3, etc.)

Informational guidance

sST2 and other biomarkers: sST2 (soluble ST2) is an emerging prognostic biomarker in heart failure with advantages such as less influence from BMI, age, or renal function; other biomarkers (galectin‑3, GDF15, copeptin, adrenomedullin) have limited or inconsistent evidence for routine clinical use and are not recommended for routine outpatient coverage without specific justification.n/a

ESC and AHA describe these biomarkers as promising but not yet established for routine practice

In the outpatient setting, qualitative (non‑quantitative) cardiac troponin assays (T or I) do not meet coverage criteria. Quantitative troponin measurement is the accepted standard for evaluation of suspected acute coronary syndrome when testing is performed at an outpatient facility capable of an adequate clinical MI evaluation; qualitative formats are explicitly excluded from coverage in this policy.

Routine use of heart-type fatty acid binding protein (H‑FABP) or copeptin as substitutes for cardiac troponin for assessment of myocardial infarction is not encouraged. The evidence summarized in this policy shows H‑FABP has inconsistent specificity compared with troponin and that studies of copeptin report mixed results; guideline reviews recommend troponin as the primary biomarker and advise that copeptin or H‑FABP should not replace troponin when contemporary troponin assays are available.

When contemporary cardiac troponin assays are available, CK‑MB and myoglobin are not useful for diagnosis of acute coronary syndromes and do not meet coverage criteria for routine diagnosis. Major guideline statements and this policy recommend cardiac‑specific troponin (I or T) as the preferred assay; CK‑MB or myoglobin may only have a limited role if troponin measurement is not possible.

The 2018 NICE guidance on chronic heart failure does not include measurement of ST2 for diagnosis and instead recommends measuring NT‑proBNP in people with suspected heart failure. While ST2 is discussed in the literature as an emerging prognostic marker in heart failure, NICE does not endorse ST2 for routine diagnostic use in chronic HF.

References supporting the policy include government and professional guidance and peer‑reviewed studies (examples: FDA substantive equivalence review; ESC, AHA/ACC, and NICE guideline documents; and original biomarker research). See the policy reference list for the full bibliographic citations.

Measurement of the following biomarkers does not meet coverage criteria in the outpatient context or for routine MI diagnosis: AST, CK/CK‑MB, CK isoenzymes, LD/LDH, myoglobin, copeptin, troponin C, C‑reactive protein, H‑FABP, ST2, and other cardiac biomarkers not listed as covered. These tests are not considered medically necessary for the indicated uses unless specific, documented justification is provided.

Covered biomarker measurements in outpatient care are limited to specific indications: quantitative troponin I or T for suspected MI (performed at a facility capable of adequate clinical MI evaluation, up to 4 tests within 72 hours), and BNP or NT‑proBNP to diagnose heart failure in dyspneic patients or to establish disease severity in chronic HF (up to 4 times per year in the outpatient setting). Documentation must support the clinical indication and facility capability.

Copeptin and H‑FABP are discussed as early markers in the literature, but this policy does not support their use as substitutes for high‑sensitivity troponin. Guideline reviews and clinical studies demonstrate inconsistent or inferior performance compared with troponin, and major professional societies recommend troponin as the primary diagnostic biomarker for MI.

Many newer biomarkers (for example, galectin‑3, copeptin, adrenomedullin, and others including routine outpatient use of ST2) are not recommended for routine clinical use by the ESC and other guideline bodies due to insufficient evidence of added clinical value. This policy therefore does not endorse routine outpatient coverage for these tests without clear clinical justification.

Procedure codes and coding guidance

Applicable CPT/HCPCS Procedure Codesmixed

No codes listed

Referenced biomarkers/tests (no billing codes listed in excerpt)mixed

No codes listed

Procedure codes listedCPT

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).
83615	Lactate dehydrogenase (LD), (LDH).
83625	Lactate dehydrogenase (LD), (LDH); isoenzymes, separation and quantitation.
83874	Myoglobin.
83880	Natriuretic peptide.

1–10 of 16

1/2

inv-21: Troponin testing frequency — up to four quantitative troponin measurements within first 72 hours

Allowed frequencyUp to four quantitative troponin measurements within the first 72 hours after initial presentation

Setting requirementPerformed at an outpatient facility capable of an adequate clinical MI evaluation

Assay typeQuantitative cardiac troponin (T or I) only; qualitative troponin in outpatient setting does not meet coverage

inv-22: BNP/NT-proBNP frequency — up to four times per year in outpatient for chronic HF

Allowed frequencyUp to four BNP or NT-proBNP tests per year in the outpatient setting for establishing disease severity in chronic heart failure

Provider action items, documentation and prior authorization

Documentation Required

Facility capability and outpatient testing

Outpatient testing for suspected acute coronary syndrome (ACS) must be performed only at facilities capable of an adequate clinical MI evaluation; testing in facilities unable to perform that evaluation (e.g., independent labs or physician offices without appropriate clinical capacity) does not meet coverage criteria.

Troponin (quantitative) permitted up to four times within first 72 hours after presentation when facility can perform clinical MI evaluation.
BNP/NT-proBNP permitted for diagnosis of heart failure in dyspneic patients and for chronic HF severity (up to four times/year outpatient).
Testing in outpatient facilities not capable of adequate MI evaluation is not covered.

Documentation Required

Troponin timing, sampling pattern, and documentation

Diagnosing myocardial infarction requires documenting a rise and/or fall of cardiac troponin (cTnI or cTnT) with at least one value above the 99th percentile upper reference limit; serial sampling is required (presentation and ~3–6 hours after symptom onset) and additional sampling beyond 6 hours when initial serial troponins are normal but clinical or ECG features suggest ACS.

Key definitions and biomarker descriptions

inv-49: Cardiac troponin (cTnI, cTnT) — definition and role

DefinitionCardiac troponins (cTnI and cTnT) are regulatory proteins with high specificity for cardiac tissue used as primary biomarkers of myocardial injury

Clinical rolePrimary biomarker for diagnosis of myocardial infarction and for short- and long-term prognostication

Isoform noteTroponin C is not used as a cardiac biomarker; troponin I and T are cardiac-specific due to unique amino acid sequences

inv-50: BNP / NT-proBNP — definition and role

DefinitionBNP and NT-proBNP are natriuretic peptides released from the heart useful in diagnosing and prognosing heart failure and evaluating dyspnea

Diagnostic roleMeasure BNP/NT-proBNP to help establish or exclude heart failure in patients presenting with dyspnea

Background and context

Cardiac biomarkers are blood measurements released from injured myocardium used for diagnosis and risk stratification of acute coronary syndromes and heart failure. Cardiac troponins (I and T) are the principal and most specific markers for myocardial infarction; BNP/NT‑proBNP are indicated for diagnosis and prognostication in heart failure. Older markers such as AST, CK, CK‑MB, LDH and myoglobin have lower specificity and are not preferred when contemporary troponin assays are available.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyBiomarkers for Myocardial Infarction and Chronic Heart Failure

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionDocument troponin timing and clinical context when requesting quantitative troponin testing up to four times within 72 hours for suspected MI.

SourceLink

On This Page

Qualitative troponin assays: Qualitative measurement of cardiac troponin (troponin T or I) in the outpatient settingNone

Does not meet coverage criteria

Measure BNP or NT‑proBNP in patients presenting with dyspnea to assist in diagnosing heart failure and for prognosis in chronic HF; interpret values in the full clinical context and consider age-specific thresholds for NT‑proBNP.

NT‑proBNP thresholds vary by age (example: NT‑proBNP >900 pg/mL ~ BNP >100 pg/mL)

Serial BNP/NT‑proBNP may reflect response to therapy; predischarge measurement can inform prognosis

BNP/NT-proBNP meets coverage criteria to diagnose heart failure in individuals presenting with dyspnea

Assay interchangeabilityBNP or NT-proBNP acceptable; interpret within full clinical context and consider age-specific NT-proBNP thresholds

inv-23: Troponin decision threshold — >99th percentile URL

Decision thresholdA myocardial infarction is designated when there is a rising and/or falling pattern with at least one cardiac troponin measurement greater than the 99th percentile of the assay-specific upper reference limit (URL)

Assay-specific noteUse the assay-specific 99th percentile URL as the decision level; high-sensitivity cTn assays are recommended for routine use

Alternative when cTn unavailableIf no cTn assay, CK-MB above its 99th percentile URL may be used as the decision level

inv-24: Presage ST2 measuring range

Presage ST2 measuring rangeManufacturer-claimed measuring range: 3.1 to 200 ng/mL (Presage ST2 Assay)

FDA clearancePresage ST2 Assay approved by FDA (Dec 9, 2011) as an in vitro diagnostic to aid prognosis in chronic heart failure

Analytical performanceManufacturer data (n≈1100) reported CV <5%, linearity, and r^2 = 0.99 supporting claimed range

inv-25: ST2 prognostic cutoffs reported (examples from studies)

Example prognostic cutoffsKy et al. (n=1,141): highest tertile ST2 >36.3 ng/mL associated with increased risk

Reported study cutoffsHou et al. identified best sST2 cut-off ≈43.43 ng/mL for predicting all-cause mortality

Other reported valuesStudies report prognostic thresholds around ~30 ng/mL and ~43.4 ng/mL depending on cohort and outcome

inv-26: SCAI post-PCI/cABG biomarker thresholds (CK-MB and cTn multipliers)

CK-MB threshold (normal baseline)Peak CK-MB within 48 hours >10× local laboratory ULN (or >5× ULN with new pathologic Q-waves in ≥2 contiguous leads or new persistent LBBB)

cTn threshold (if no CK-MB available, normal baseline)cTn (I or T) within 48 hours >70× local laboratory ULN (or >35× ULN with new pathologic Q-waves in ≥2 contiguous leads or new persistent LBBB)

Elevated baseline scenarioIf baseline CK-MB or cTn elevated but stable or falling, a rise equal to the above absolute increments from the most recent pre-procedure level defines clinically relevant MI

inv-27: Troponin sampling/threshold operational guidance

Recommended thresholdsUse 99th percentile thresholds or thresholds at/near the assay limit of detection for high-sensitivity troponin assays

Sampling interval guidanceWhen taking multiple samples, obtain initial assessment sample followed by a second sample 30 minutes to 3 hours after (NICE recommends 30 min–3 h)

Operational documentationRecord timing of symptom onset or presentation and troponin measurement times; document rising/falling pattern with at least one value above 99th percentile when diagnosing MI

Document symptom onset time or, if unknown, use time of presentation as onset for timing troponin measurements.
Record exact clock times for each troponin measurement to demonstrate rising/falling pattern.
High-sensitivity troponin assays are recommended for routine clinical use when available.

Denial Risk

Use of non-troponin markers (CK‑MB, myoglobin, H‑FABP, etc.)

CK‑MB, myoglobin, and other non‑troponin markers are not recommended when troponin assays (contemporary/high‑sensitivity) are available; these markers are less sensitive/specific and generally do not meet coverage criteria for MI diagnosis in the outpatient setting.

CK‑MB or myoglobin may be considered only if troponin is unavailable — CK‑MB decision level is the 99th percentile of the URL and sex‑specific values should be used.
Qualitative troponin testing is not covered in the outpatient setting.
Markers such as AST, CK, LDH, myoglobin, H‑FABP, copeptin, troponin C, CRP, and others listed do not meet coverage criteria for MI diagnosis.
ASCP advises against CK‑MB or myoglobin to diagnose acute MI; prefer troponin I or T.

Note

Conflicts with government policy

When there is any conflict between this policy and applicable government coverage (e.g., Medicare LCDs/NCDs or state Medicaid rules), the relevant government policy takes precedence.

Consult CMS Medicare Coverage Database and applicable state Medicaid sites for the most up‑to‑date government determinations.

Note

Prior authorization and step therapy (informational)

No operational prior authorization or step‑therapy requirements are specified in this section of the policy. References and guideline recommendations are provided for clinical and documentation expectations but do not themselves constitute an authorization mechanism.

Procedure codes listed in the document may remain subject to payer prior authorization or billing review per plan-specific rules — check member benefits.
References (AHA/ACC, ESC, NICE, FDA, ASCP, etc.) inform clinical expectations but do not impose operational authorization steps within this policy.

Prognostic/serial useSerial BNP/NT-proBNP may reflect response to therapy and can be used for prognosis in chronic or acutely decompensated HF; interpret NT-proBNP with age-specific thresholds

inv-51: Troponin I and T — cardiac-specific isoforms

IsoformsTroponin I (TnI) and Troponin T (TnT) are the cardiac-specific isoforms used as biomarkers of myocardial injury

Specificity basisHigh cardiac specificity is due to distinct amino acid sequences encoded by different genes compared with skeletal muscle isoforms

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

inv-52: BNP / NT-proBNP — natriuretic peptides and thresholds

Biomarker classBNP and NT-proBNP are natriuretic peptides produced from proBNP cleavage; BNP mainly from left ventricle

Threshold exampleNT-proBNP >900 pg/mL approximates BNP >100 pg/mL as an equivalence example

Clinical interpretationValues vary with age and clinical context; use with complete clinical evaluation rather than in isolation

inv-53: sST2 (soluble ST2) — biomarker of stress and fibrosis

DefinitionsST2 (soluble ST2) is a member of the interleukin-1 receptor family; elevated levels reflect cardiomyocyte stress and fibrosis and provide prognostic information in heart failure

Clinical contextsST2 can add prognostic value to natriuretic peptides and is less affected by BMI, age, and renal function in some studies

Assay examplePresage ST2 (Critical Diagnostics) is a proprietary assay used to measure sST2 for prognostic assessment in chronic HF

inv-54: ACS / MI biomarkers — troponin primary, CK-MB/myoglobin less useful

Primary biomarkerCardiac troponin (I or T) is the recommended primary biomarker for diagnosis of acute myocardial infarction

Older markers discouragedCK-MB and myoglobin are not useful for ACS diagnosis when contemporary troponin assays are available

Substitutes only when necessaryCK-MB may be used as an alternative if troponin unavailable, but troponin is preferred

inv-55: SCAI clinically relevant post-revascularization MI definitions

SCAI definition basisSCAI defines clinically relevant post-revascularization MI using CK-MB or cTn multipliers relative to local ULN

CK-MB multiplierCK-MB peak within 48 hours >10× ULN (or >5× ULN with new Q-waves or persistent LBBB) for normal baseline

cTn multiplierIf CK-MB unavailable, cTn >70× ULN within 48 hours (or >35× ULN with new Q-waves or persistent LBBB) for normal baseline

inv-56: High-sensitivity cardiac troponin — definition and NICE recommendation

DefinitionHigh-sensitivity cardiac troponin assays have analytic sensitivity allowing earlier rule-out of NSTEMI; NICE recommends specific high-sensitivity assays for ED rule-out

Threshold guidanceNICE recommends using thresholds at or near the limit of detection or the 99th percentile depending on assay and taking serial samples 30 minutes to 3 hours apart when using multiple samples

Assay examplesNICE lists approved high-sensitivity troponin I and T assays (e.g., ARCHITECT, Elecsys, VIDAS, VITROS, Alinity, Dimension, Atellica) for earlier rule-out

inv-57: Laboratory-developed test (LDT) — CLIA regulation and validation

DefinitionLaboratory-developed test (LDT) is an in-house test regulated by CMS under CLIA '88 as high-complexity testing and requires in-house validation

FDA statusLDTs are not approved or cleared by the FDA; FDA clearance is not currently required for clinical use

Documentation expectationLabs must validate LDT performance and CLIA compliance may be required in documentation for payer review

inv-58: ST2 — soluble interleukin-1 receptor family member used prognostically

DefinitionST2 is a soluble member of the interleukin-1 receptor family (sST2) used as a prognostic biomarker in heart failure

Biologic rolesST2 binds IL-33, blocking IL-33/ST2L cardioprotective signaling, which is associated with hypertrophy, fibrosis, and dysfunction in experimental models

Clinical evidenceConsensus panels and multiple studies (e.g., Ky et al., Januzzi consensus) identify sST2 as an emerging prognostic biomarker in HF

inv-59: Copeptin — early marker proposed for AMI

DefinitionCopeptin is the C-terminal fragment of pro-vasopressin proposed as an early marker for acute myocardial infarction

Diagnostic performanceSome studies show copeptin improves early AMI diagnostic performance when combined with troponin, particularly within very early symptom onset

Coverage stanceRoutine use of copeptin as substitute for troponin is not supported and does not meet coverage criteria in this policy

inv-60: HFABP — heart-type fatty acid-binding protein evaluated for early AMI diagnosis

DefinitionHeart-type fatty acid-binding protein (HFABP) is a small cytoplasmic cardiomyocyte protein evaluated for early diagnosis of AMI

Clinical performanceHFABP has been evaluated but shows inferior or inconsistent performance compared with contemporary troponin assays; routine substitution is not encouraged

Coverage stanceRoutine use of HFABP as a substitute for troponin does not meet coverage criteria