Medical Coverage Policy Laboratory Tests Post Transplant and for Heart Failure

Coverage Summary

This policy provides coverage criteria for noninvasive molecular and biomarker tests to detect and monitor allograft rejection in heart, lung, and kidney transplant recipients and for biomarkers used in heart failure management (for example, BNP/NT-proBNP and sST2). It applies to Medicare Advantage and Commercial products and defines medical necessity, prior authorization, and coding guidance for listed tests; it is effective 2025-08-01 (policy effective date) and notes a CPT code change for AlloSure Kidney effective 2025-04-01 (use 81479 prior to that date).

Medical-Necessity Criteria — General

General Medical Necessity for Molecular/Multianalyte Tests (Effective 8/1/2025)

Effective 8/1/2025, the following test(s) are considered medically necessary when the medical criteria in the online authorization tool for participating providers are met:

ALL of the following

Listed test and authorization tool: Test is listed in policy and the medical criteria in the online authorization tool for participating providers are met
Prior authorization required for Medicare Advantage and recommended for Commercial Products via the online tool for participating providers

Medical-Necessity Criteria — Specific Tests & Uses

Tests That May Be Medically Necessary when Specific Medical Criteria Met

The following tests may be medically necessary when ALL of the following medical criteria below are met:

Medical criteria for use

Clinical status determinations: Test provides information about at least one of the following clinical status determinations: Active Rejection (AR) status
Intended use includes assessment of cellular or antibody-mediated rejection (ACR or AMR) status
Immunosuppression assessment: Test may assist in evaluation of adequacy of immunosuppression, wherein a non-invasive or minimally invasive test can be used in lieu of tissue biopsy when information from tissue would be used to make a management decision regarding immunosuppression

Not Covered / Not Medically Necessary

Evidence was judged insufficient or inconsistent for several tests because diagnostic and prognostic performance is limited, clinical utility has not been demonstrated, or results are variable across studies. Examples include the single diagnostic study for Heartsbreath with limited validation and insufficient clinical utility, observational validation studies for myTAIHEART that showed high NPV at donor-fraction cutoffs but lacked evidence of improved net health outcomes, mixed data for dd-cfDNA assays (Prospera, AlloSure, AlloSure Lung) showing variable discrimination between rejection and other injury, and correlative but not consistently additive prognostic value for Presage ST2 versus natriuretic peptides. These concerns underpin the policy’s determinations of not covered/insufficient and selective medical necessity (evidence labels: Heartsbreath diagnostic study NPV; myTAIHEART validation; Prospera surveillance threshold; AlloSure assay; Presage ST2).

Coding

Medically Necessary / May be Medically Necessary CPT CodesCPTCovered

0540U	AlloSure Kidney (New Code Effective 4/1/2025; prior to 4/1/2025 use 81479)
0118U	TRACTM dd-cfDNA (formerly Viracor TRAC dd-cfDNA)
81595	AlloMap (CareDx)
0508U	VitaGraftTM Kidney Baseline + 1st Plasma Test
0509U	VitaGraftTM Kidney Subsequent
81479	Unlisted molecular pathology procedure — used for several AlloSure/HeartCare/AlloSure Lung prior to dedicated codes
0493U	ProsperaTM (quantification of donor-derived cfDNA, Natera)
81599	Unlisted multianalyte assay with algorithmic analysis (QSant)
0055U	myTAIHEART — cardiology PCR assay of 96 DNA targets (listed as test code)
0087U	Molecular Microscope MMDx–Heart mRNA gene expression profiling (listed)

1–10 of 11

1/2

Not Covered / Not Medically Necessary CPT CodesCPTNot Covered

83006	Presage ST2 Assay (Growth stimulation expressed gene 2, ST2)
O018M	PleximarkTM (measurement of donor and third-party-induced CD154+ T-cytotoxic memory cells) - listed as not covered code

Notesmixed

0540U_note	AlloSure Kidney CPT 0540U is a new code effective 2025-04-01; prior to 2025-04-01 use unlisted CPT 81479 as indicated in policy.
81479_note	Prior to introduction of specific CPT codes for some tests (eg, AlloSure Kidney before 0540U), CPT 81479 (Unlisted molecular pathology procedure) or other unlisted codes (eg, 81599) were used per coding guidance.

When a specific CPT code is not available for a test referenced in this policy, use the applicable unlisted CPT codes (for example, 81479 for unlisted molecular pathology procedures or 81599 for unlisted multianalyte assays with algorithmic analysis) as described in the billing guidance. The policy also notes that AlloSure Kidney has a new CPT code 0540U effective 2025-04-01, with 81479 to be used prior to that date.

Provider Actions & Billing Rules

Prior Authorization

Prior authorization required/recommended

Prior authorization is required for Medicare Advantage and recommended for Commercial products for the listed tests. Affected CPT codes include: 0540U, 0118U, 81595, 0508U, 0509U, 81479, 81599, 0493U. Use the online authorization tool for participating providers. Participating providers must follow the online tool to obtain authorization.

Affected codes: 0540U, 0118U, 81595, 0508U, 0509U, 81479, 81599, 0493U
Authorization via the online authorization tool for participating providers
Required for Medicare Advantage; recommended for Commercial products

Documentation Required

Ordering physician must obtain authorization

Only the ordering physician may obtain authorization and participate in authorization or appeal processes. Laboratories or their representatives are prohibited from obtaining authorization on behalf of the ordering physician. If a laboratory provides a laboratory service that has not been authorized, the service will be denied and financial liability will be assigned to the participating laboratory.

Background, Evidence Summary & Definitions

Biopsy remains the historical criterion standard for diagnosing allograft rejection but has important limitations including interobserver variability, sampling limitations, and procedural risks. These limitations have driven investigation of less invasive approaches such as quantification of donor-derived cell-free DNA (dd-cfDNA) and gene-expression profiling (GEP) to detect graft injury or rejection. dd-cfDNA assays (eg, AlloSure, Prospera) and combined GEP/dd-cfDNA approaches (eg, HeartCare) offer noninvasive measures of allograft injury and, in some settings, may provide incremental information to guide management; however, the overall evidence varies by test and organ type and is not uniformly sufficient to establish clinical utility for all listed assays.

Evidence	Summary / Key detail
Heartsbreath NPV
Negative predictive value reported 97.2% for grade 3 (now 2R) rejection in a single diagnostic study; sensitivity 78.6%; evidence judged insufficient
myTAIHEART validation
Donor-fraction cutoff ~0.3%–0.32% in observational/validation studies produced high NPV to rule out Grade ≥2R rejection; evidence insufficient for net health outcome
Prospera surveillance threshold
Manufacturer recommends surveillance at 1,2,3,4,6,9,12 months and quarterly thereafter; ≥1% dd-cfDNA indicates increased risk for active renal transplant rejection
AlloSure assay note
Targeted NGS assay quantifying dd-cfDNA (266 SNP panel); provides incremental information when used in combination (eg, with AlloMap/HeartCare)
Presage ST2 summary
Correlational studies and meta-analyses show association of sST2 with mortality and with rejection in small studies, but no consistent added prognostic value over natriuretic peptides; evidence insufficient to support management changes
References cited
Multiple peer-reviewed studies, clinical guidelines, and vendor resources spanning 1998–2023

Glossary: dd-cfDNA — donor-derived cell-free DNA quantified as the percentage of total cell-free DNA and used as a marker of allograft injury/rejection; AR — Active Rejection; ACR — Acute Cellular Rejection; AMR — Antibody-Mediated Rejection.

Medicare Determinations

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

MolDX: Molecular for Solid Organ Allograft Rejection
L38629
LCD

MolDX: Molecular Diagnostic Tests (MDT)
L35160
LCD

MolDX: Molecular Testing for Solid Organ Allograft Rejection
L38680
LCD

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