CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Transplant and for Heart Failure

Defines medical necessity, coverage, and prior authorization requirements for specific laboratory tests used to assess allograft rejection in heart and kidney transplant recipients and biomarkers in heart failure for Medicare Advantage Plans and Commercial Products (partial document: Part 1 of 2).

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyTransplant and for Heart Failure

Policy CodePolicy N/A

Change TypeNo material change

Effective Date06/01/2021

Next Review Date

Key ActionObtain prior authorization for AlloSure Heart and AlloSure Kidney when performed for Medicare Advantage members; prior authorization is required to determine coverage and medical necessity.

SourceLink

POLICY UPDATE CHANGES

No material clinical/coverage changes - has_material_change=false

1Coded Covered Test (Medicare Advantage): AlloMap

2Tests requiring prior authorization (Medicare Advantage)

6Total tests addressed in policy (listed)

31Cited References

Coverage Summary

This policy (effective 06/01/2021, last reviewed 02/16/2021) provides a focused overview of coverage and medical necessity criteria for laboratory tests used to assess allograft rejection and biomarkers in heart failure. The coverage stance is mixed: AlloMap (gene expression profiling) is covered for Medicare Advantage, AlloSure Heart and AlloSure Kidney have defined Medicare Advantage medical necessity criteria (and require prior authorization), while Heartsbreath, myTAIHEART, and the Presage® ST2 Assay are not covered for Medicare Advantage due to insufficient evidence. For Commercial products listed in this policy, all addressed tests (AlloMap, AlloSure Heart, AlloSure Kidney, Heartsbreath, myTAIHEART, Presage ST2) are considered not medically necessary. The tests specifically addressed are AlloMap, AlloSure Heart, AlloSure Kidney, Heartsbreath, myTAIHEART, and Presage® ST2.

Key thresholds and quick facts

AlloSure Heart timing>= 55 days post-transplant

AlloSure Kidney timing>= 2 weeks post-transplant

myTAIHEART cutoff (validation)0.32% donor fraction (validation study)

myTAIHEART cutoff (prospective)0.3% donor fraction (prospective study)

Total tests addressed6 tests listed in policy

Referenced citations count31 references cited

Medical-Necessity Criteria

AlloSure Heart - Medicare Advantage Medical Necessity

AlloSure® Heart may be considered medically necessary when all of the following criteria are met:

AlloSure Heart criteria

Conjunction with AlloMap: It is used in conjunction with AlloMap®
Clinical suspicion: To assess the probability of allograft rejection in heart transplant recipients with clinical suspicion of rejection
Biopsy decision: To inform clinical decision-making about the necessity of a heart biopsy in such patients at least 55 days post-transplant in conjunction with standard clinical assessment>= 55 days post-transplant

AlloSure Kidney - Medicare Advantage Medical Necessity

AlloSure® Kidney may be considered medically necessary when all of the following criteria are met:

AlloSure Kidney criteria

Clinical use: It is used to assess the probability of allograft rejection in kidney transplant recipients with clinical suspicion of rejection
Biopsy decision: To inform clinical decision-making about the necessity of renal biopsy in such patients at least 2 weeks post-transplant in conjunction with standard clinical assessment>= 2 weeks post-transplant

Prior Authorization Requirements - Medicare Advantage Plans

Tests requiring prior authorization for Medicare Advantage Plans:

PA requirements

AlloSure Heart PA: AlloSure Heart requires prior authorization
AlloSure Kidney PA: AlloSure Kidney requires prior authorization
Unlisted CPT PA: Unlisted CPT codes (eg, 81479 for AlloSure) require prior authorization to determine coverage/medical necessity

Authorization Process Restriction

Restrictions on who may obtain authorization:

Authorization process restriction

Ordering physician only: Only the ordering physician shall be involved in the authorization, appeal or other administrative processes related to prior authorization/medical necessity
Laboratory prohibition: Laboratories or laboratory representatives are prohibited from obtaining clinical authorization or participating in the authorization process on behalf of the ordering physician; violations may lead to termination from the BCBSRI provider network and financial liability for unauthorized services

Covered vs Not Covered - Medicare Advantage Plans

Coverage determinations for Medicare Advantage Plans:

Medicare Advantage coverage determinations

AlloMap covered: AlloMap is covered
AlloSure Heart conditional: AlloSure Heart may be considered medically necessary when specified criteria are met
AlloSure Kidney conditional: AlloSure Kidney may be considered medically necessary when specified criteria are met
Heartsbreath not covered: Heartsbreath is not covered (evidence insufficient)

Commercial Products Coverage Position

Coverage determinations for Commercial Products (per this document):

Commercial products position: All listed tests (AlloMap, AlloSure Heart, AlloSure Kidney, Heartsbreath, myTAIHEART, Presage® ST2 Assay) are considered not medically necessary

Coding

Covered CPT (Medicare Advantage)CPTCovered

81595

Cardiology (heart transplant), mRNA, gene expression profiling by real-time quantitative PCR of 20 genes..., algorithm reported as a rejection risk score (AlloMap)

Not Covered / Not Medically Necessary CPT (both Medicare Advantage and Commercial as listed)CPTNot Covered

83006	Growth stimulation expressed gene 2 (ST2, Interleukin 1 receptor like-1) (Presage® ST2 Assay)
0055U	Cardiology (heart transplant), cell-free DNA, PCR assay of 96 DNA target sequences (myTAIHEART)

Unlisted CPT for AlloSure Heart/Kidney and Heartsbreath (no specific CPT)CPT

81479	Unlisted molecular pathology procedure (use for AlloSure Heart and AlloSure Kidney). Requires prior authorization for Medicare Advantage Plans and Commercial Products
unlisted_pre2021	0085T Breath test for heart transplant rejection (Heartsbreath) - use for dates of service prior to 2021-01-01

Provider Actions & Billing Rules

Prior Authorization

Prior authorization required for AlloSure Heart and Kidney

Prior authorization is required for AlloSure Heart and AlloSure Kidney for Medicare Advantage members; report these services using Unlisted CPT when no specific CPT exists.

81479

Billing Rule

Use appropriate unlisted CPT codes when specific CPT is unavailable

When there is no specific CPT code for a service referenced in this policy, report the most appropriate unlisted CPT code. For AlloSure Heart and AlloSure Kidney use unlisted molecular pathology code 81479. For Heartsbreath use the most appropriate unlisted CPT for services dated on or after 2021-01-01; for dates of service prior to 2021-01-01 use 0085T.

81479
0085T

Documentation Required

Ordering physician must handle authorization and appeals

Only the ordering physician may be involved in the authorization, appeal, or other administrative processes related to prior authorization/medical necessity. Laboratories or laboratory representatives are prohibited from obtaining authorization or participating in the authorization process on behalf of the ordering physician; violations may result in termination from the BCBSRI provider network and financial liability for unauthorized services.

Documentation Required

Member financial consent when services non-covered

If services are determined to be not medically necessary or are non-covered benefits, providers may not charge the member unless the member has been informed and has agreed in writing in advance to continue treatment at their own expense.

Documentation Required

Policy informational use and member benefit determination; Policy revisions and inquiries

This policy is provided for informational purposes only. Benefits and eligibility are determined by the member's subscriber agreement or employer agreement, which supersede this policy. For member-specific benefit information, contact the provider call center. BCBSRI reserves the right to review and revise this policy at any time.

Background & Evidence Summary

Clinical assessment and noninvasive imaging for heart failure and transplant surveillance have important limitations: symptoms and signs may poorly correlate with objective measures of cardiac dysfunction and often present late, and endomyocardial biopsy—while the criterion standard for transplant rejection—has interobserver variability and procedural risks. These limitations have driven interest in circulating biomarkers and other noninvasive tests to improve detection, risk stratification, and to potentially reduce reliance on invasive biopsy.

For heart failure, circulating biomarkers (eg, BNP/NT-proBNP) are established reference tests for diagnosis and prognosis, and newer markers such as soluble ST2 (measured by the Presage® ST2 Assay) have been investigated because they reflect remodeling and myocardial stress but currently lack sufficient evidence to determine effects on health outcomes or to replace standard biomarkers in management.

For transplant rejection, noninvasive approaches evaluated include gene expression profiling (AlloMap) and donor-derived cell-free DNA assays (AlloSure, myTAIHEART), as well as breath volatile organic compound analysis (Heartsbreath). These tests aim to identify rejection or to inform the need for biopsy: AlloMap uses peripheral blood gene expression profiling, AlloSure and myTAIHEART quantify donor-derived cell-free DNA to estimate donor fraction, and Heartsbreath analyzes breath markers of oxidative stress. The policy addresses the following specific tests: AlloMap, AlloSure Heart, AlloSure Kidney, Heartsbreath, myTAIHEART, and Presage® ST2 Assay.

Evidence item	Summary
AlloMap FDA status
FDA-approved IVDMIA to aid identification of heart transplant recipients with low probability of moderate/severe acute cellular rejection when used with standard clinical assessment; characterized as a rule-out test and can complement dd-cfDNA testing
sST2 evidence summary
Observational studies and meta-analyses show sST2 associates with mortality and may predict rejection, but evidence is insufficient to determine effects on health outcomes or clinical utility for management or transplant prediction
myTAIHEART validation
Validation study (158 biopsy-plasma pairs) found donor fraction cutoff 0.32% with 100% NPV for Grade >=2 rejection; prospective study found ~0.3% cutoff; evidence insufficient for health outcomes
Heartsbreath diagnostic study
Single diagnostic accuracy study: NPV 97.2% for grade 3 (now 2R), sensitivity 78.6%, specificity 62.4%; single study inadequate to establish clinical validity or utility
AlloSure renal evidence
Small diagnostic studies in kidney transplant showed NPV ~84% for moderate-to-severe rejection; threshold not prespecified; evidence insufficient for health outcomes
Reference count
31 citations referenced in policy (selected studies on ST2, AlloMap, dd-cfDNA, microRNAs, hs-troponin)

Definitions

dd-cfDNADonor-derived cell-free DNA

sST2Soluble suppression of tumorigenicity-2 protein biomarker

ACRAcute cellular rejection

Name	Number	Type	Effective Date
HEARTSBREATH Test for Heart Transplant Rejection
260.10
NCD

MolDX: Molecular Diagnostic Tests (MDT)
L35160
LCD

MolDX: Allosure® or Equivalent Cell-Free DNA Testing for Kidney and Heart Allografts
L38355
LCD

OpenPayer

Transplant and for Heart Failure

Coverage Summary

Medical-Necessity Criteria

Coding

Provider Actions & Billing Rules

Background & Evidence Summary

Medicare Determinations

Revision History