Medical Policy

 

Subject: Laboratory Testing as an Aid in the Diagnosis of Heart Transplant Rejection
Document #: TRANS.00025 Publish Date:    06/06/2018
Status: Reviewed Last Review Date:    05/03/2018

Description/Scope

This document addresses specific noninvasive laboratory tests for the early detection of rejection following a heart transplant.  This includes the Heartsbreath test (Menssana Research, Inc. Fort Lee, NJ), which measures the chemical byproducts of allograft rejection and has been investigated to potentially make the process of monitoring heart transplant recipients safer and less complicated.  Also addressed in this document is the AlloMap® molecular expression testing (CareDx®, Inc., Brisbane, CA) which has also been investigated as a noninvasive method of determining the risk of rejection in heart transplant recipients.

Even with modern drug therapy, rejection remains a constant hazard, and transplant recipients must be tested repeatedly for signs of renewed rejection.  Currently, the gold standard to detect heart transplant rejection is endomyocardial biopsy.  This is typically performed weekly for the first 6 weeks, biweekly until the third month, monthly to 6 months and then every 1 to 3 months, as indicated.

Position Statement

Medically Necessary:

AlloMap molecular expression testing is considered medically necessary as a non-invasive method of determining the risk of rejection in heart transplant recipients between 1 and 5 years post-transplant.

Investigational and Not Medically Necessary:

Breath testing with the Heartsbreath test is considered investigational and not medically necessary for use as an aid in the diagnosis of heart transplant rejection.

AlloMap molecular expression testing is considered investigational and not medically necessary when the criteria above are not met.

Rationale

Breath Test

Heartsbreath (Breath test for Grade 3 heart transplant rejection), manufactured by Menssana Research, Inc., (Fort Lee, NJ) received U.S. Food and Drug Administration (FDA) clearance on February 24, 2004 under the Humanitarian Device Exemption (HDE)* program with the following indications for use:

The Heartsbreath test is indicated for use as an aid in the diagnosis of grade 3 heart transplant rejection in patients who have received heart transplants within the preceding year.  The Heartsbreath test is intended for use as an adjunct to, and not as a substitute for, endomyocardial biopsy.  The use of the device is limited to patients who have had endomyocardial biopsy (EMB) within the previous month (FDA, 2004).

The Heartsbreath test works on the principle that rejection of the transplanted heart is accompanied by oxidative stress that degrades membrane polyunsaturated fatty acids, evolving alkanes and methylalkanes that are excreted in the breath as volatile organic compounds (VOCs).  The individual breathes for 2 minutes through a disposable mouthpiece attached to a breath collecting device, which then analyzes the VOCs in alveolar and room air and interprets the values, using a proprietary algorithm to predict the probability of Grade 3 heart transplant (HT) rejection. 

The Heartsbreath test should not be used for individuals who have received an HT more than 1 year ago, or have a Grade 4 HT rejection, because Heartsbreath has not been evaluated in these groups.

FDA clearance was based on the results of the Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels (HARDBALL) Study, which was sponsored by the National Heart Lung and Blood Institute (NHLBI).  In this 3-year multicenter study, investigators evaluated a new marker of HT rejection, the breath methylated alkane contour (BMAC).  In the HARDBALL study, 1061 breath VOC samples were collected from 539 HT recipients at seven sites on the day of scheduled EMB.  The gold standard of rejection was the concordant set of International Society for Heart and Lung Transplantation (ISHLT) grades in biopsies read by two cardiac pathologists.  Results included concordant biopsies of:

A combination of 9 VOCs in the BMAC identified Grade 3 rejection (sensitivity 78.6%; specificity 62.4%; cross-validated sensitivity 59.5%; cross-validated specificity 58.8%; positive predictive value [PPV] 5.6%; negative predictive value [NPV] 97.2%).  Site pathologists identified the same cases with sensitivity of 42.4%, specificity 97.0%, PPV 45.2% and NPV 96.7%.  The authors concluded that a breath test for markers of oxidative stress was more sensitive and less specific for Grade 3 HT rejection than a biopsy reading by a single on-site pathologist, but the NPV of the two tests were similar.  They concluded that a negative screening breath test could potentially identify transplant recipients at low risk of Grade 3 rejection and obviate the need for EMB in this group, thereby reducing the overall number of EMBs performed, which was estimated to be by as much as 50% (Phillips, 2004).

Currently, there is inadequate evidence in the published literature to demonstrate the safety, efficacy, and clinical utility of the Heartsbreath test in the management of rejection surveillance following HT.  Large trials are needed to further define the role of this technology and demonstrate how use of this test will impact treatment management.

AlloMap Molecular Expression Testing

The AlloMap molecular expression blood test was developed by XDx, Inc. (South San Francisco, CA), now known as CareDx, Inc., Brisbane, CA.  In 2008, FDA 510(k) clearance as a Class II approval was granted for AlloMap Molecular Expression Testing as an in-vitro, diagnostic, multivariate, index assay test service, which assesses the gene expression profile of RNA isolated from peripheral blood mononuclear cells for the following indication: 

To aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing in conjunction with standard clinical assessment.  AlloMap is indicated for use in heart transplant recipients who are 15 years of age or older and at least 2 months (greater than or equal to 55 days) post-transplantation (FDA, 2008).

The test assesses the expression of 20 genes, about half of which are directly involved in rejection while the remainder provide other information needed for rejection risk assessment.  It is hoped the results of this test will decrease the number of necessary EMBs.  Among the proposed benefits are the AlloMap test's ability to differentiate mild rejection, for which histologic findings may be the least accurate, and the potential for monitoring physiologic responses to steroid weaning.  It has been recognized that the test is not effective at monitoring rejection within the first 6 months of transplantation, and it is yet unclear what a high AlloMap score might mean in the setting of no histologic rejection. 

These patterns of gene expression, detected in peripheral blood by the AlloMap testing, were studied in the Cardiac Allograft Rejection Gene Expression Observation Study (CARGO), which included eight U.S. cardiac transplant centers where 650 HT recipients were tested.  Results of the CARGO study have appeared in abstracts presented at the 2005 annual meeting of the ISHLT.  While the results were promising, the data was considered inadequate to permit firm scientific conclusions regarding how use of this test will impact the management of HT recipients (Deng, 2006).  There have been subsequent validation studies and sub-study analyses of the CARGO results which provided additional data regarding the potential utility of the AlloMap test in detecting transplant rejection (Bernstein, 2007; Mehra, 2007b; Mehra, 2008).  More recent results of the CARGO and the CARGO II trial, a European based observational study to further validate the gene expression profiling (GEP) test performance of AlloMap, have been published with findings that reflect similar results.  For greater than or equal to 2-6 months and greater than 6 months post-transplantation, the CARGO II GEP score performance (AUC-ROC=0.70 and 0.69) is similar to the CARGO study results (AUC-ROC=0.71 and 0.67).  It was the opinion of the trial investigators that the low prevalence of ACR contributed to the high NPV and limited PPV of GEP testing. The authors concluded that choice of threshold score for the practical use of GEP testing with AlloMap should consider the overall clinical assessment of the individual’s baseline risk for rejection (Crespo-Leiro, 2015; 2016).

Results of another trial were published in 2010.  The Invasive Monitoring Attenuation through Gene Expression (IMAGE) trial , which was sponsored by the manufacturer of AlloMap (XDx, Inc.), was a randomized, event-driven, noninferiority trial which was conducted at 13 U.S. transplant centers between January 2005 and October 2009 (with median follow-up of 19 months).  This trial included 602 selected transplant recipients who had undergone a transplant more than 6 months prior and who were considered at low risk for rejection.  The purpose of this study was to compare rejection outcomes between those who underwent routine EMB and those who were monitored with the AlloMap GEP test.  The primary outcome was the first occurrence of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation.  Results indicated that a strategy of monitoring for rejection that involved GEP, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies.  During the median follow-up period (19 months), subjects who were monitored with AlloMap and those who underwent routine EMB had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio [HR] with GEP, 1.04; 95% confidence interval [CI], 0.67 to 1.68).  The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; p=0.82).  Although the limited power of the study did not allow for firm conclusions regarding the utility of AlloMap as a substitute for EMB, the authors concluded that GEP of peripheral blood specimens may offer a reasonable alternative to routine EMB, for monitoring cardiac transplant rejection, if the interval since transplantation is at least 6 months and the individual is considered to be at low risk for rejection (Pham, 2010).

In 2010, the ISHLT issued guidelines for the care of HT recipients which included the following: 

Another 2010 portion of the ISHLT guideline titled, “Task Force 2: Immunosuppression and Rejection” noted the following regarding the grading scale for risk of ACR in HT recipients:

Due to intra- and interobserver variability in the determination of the different grades of mild or moderate rejection and the observation that grades 1 and 2 were mostly self-limited, a revised heart allograft rejection grading system was published in 2005 as follows (Stewart, 2005):

The recommendation for AlloMap is based on the results of the CARGO and IMAGE trials (Costanzo, 2010).

In summary, the current ISHLT recommendations for the use of AlloMap in limited clinical protocols, the results of the IMAGE trial, and input from the transplant practice community support the use of AlloMap to assess risk for ACR in clinically stable HT recipients between 1 and 5 years post-transplant.

Background/Overview

Breath Test

Although the current gold standard test for detecting rejection is EMB, this is limited in accuracy, has a high degree of inter-observer variability, and may yield tissue that is not representative of the overall pathology.  It is also invasive and can lead to infections, arrhythmias, or ventricular perforation.  Despite these limitations, the breath test is currently not established as a substitute for EMB.

*Note: A Humanitarian Use Device (HUD) is a device that has been given special approval by the FDA under the Humanitarian Device Exemption (HDE) regulations and is utilized in special circumstances where a condition is so rare (fewer than 4000 individuals in the U.S. per year) that testing of large numbers of subjects is not feasible.  In these special situations, the FDA may grant an HDE provided that: the device does not pose an unreasonable or significant risk of illness or injury; and the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.  Additionally, the FDA notes that the applicant must demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.  The labeling for an HUD must state that the device is a Humanitarian Use Device and that, although the device is authorized by federal law, the effectiveness of the device for the specific indication has not been demonstrated. (FDA, 2004)

AlloMap Molecular Expression Testing

The California Technology Assessment Forum (CTAF) conducted a technology assessment of GEP for the diagnosis of HT rejection in 2006, at which time it was determined that the use of GEP did not meet CTAF criteria when used to manage HT patients.  The CTAF assessment stated that:

Gene expression profiling offers the potential for a non-invasive test that may replace endomyocardial biopsy as the gold standard for transplant rejection.  However, given the history of poor reproducibility of other gene expression profiles in the recent past, it is prudent to require independent confirmation of the CARGO study results before widespread adoption of the AlloMap gene expression profile to monitor heart transplant patients for early detection of rejection (CTAF, 2006).

This initial CTAF determination was based on concerns around the post-hoc change in the threshold used to define a positive test result in the CARGO study and the small size of this primary validation study, in addition to the fact that there were no studies, published to date, comparing the clinical outcomes of individuals monitored with GEP to those monitored with EMB (CTAF, 2006).

In 2010, the CTAF conducted a systematic re-review of available published evidence focusing on results of the AlloMap test which included six observational studies and one randomized trial.  Three of the publications included in this review reported on subsets of participants from the CARGO trial, as well as results of the IMAGE trial and concluded that, “This technology meets CTAF's assessment criteria for safety, effectiveness and improvement in health outcomes when used to manage HT patients at least one year post-transplant.” The CTAF assessment included the following conclusions:

The AlloMap gene expression profile has a high negative predictive value, but a low positive predictive value. Thus, it may be useful to avoid biopsy in stable patients, but the high false positive rate precludes its use to definitively diagnose acute cellular rejection.  Endomyocardial biopsies will still need to be performed in all patients with elevated AlloMap scores and all patients with clinical signs of rejection.  The IMAGE trial provides data supporting the non-inferiority of a monitoring strategy for heart transplant patients incorporating the AlloMap gene expression profile in lieu of routine endomyocardial biopsy.  However, the data only support such strategies in patients more than a year post-transplant.  More data are needed to confirm the tests utility earlier in the post-transplant period when the majority of endomyocardial biopsies are performed (CTAF/Tice, 2010).

In 2011, the Blue Cross Blue Shield Association published a Technology Assessment Report of GEP as a noninvasive method to monitor for cardiac allograft rejection.  This review and analysis of the available published evidence concluded that the use of GEP as a noninvasive method to monitor for cardiac allograft rejection does not meet the TEC criteria.  The following are some summarized conclusions:

Although a higher score is associated with a greater likelihood of rejection class 3A or higher, the diagnostic characteristics of AlloMap® testing are uncertain. Study methods are unclear, study samples are incompletely described, numbers of cases of rejection are apparently small, and cutoff scores appear to have been determined post hoc. The sensitivity of the test for detecting rejection is uncertain (TEC, 2011).

Definitions

Allograft rejection, also referred to as acute cellular rejection (ACR): The recipient’s immune system rejects the donor heart.

Endomyocardium: The innermost lining of the heart.

Endomyocardial biopsy (EMB): A tissue sample of the endomyocardium.

Heart transplant (HT): Removal of a human heart and replacing it with a donor heart.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

CPT

 

81595

Cardiology (heart transplant), mRNA, gene expression profiling by real-time quantitative PCR of 20 genes (11 content and 9 housekeeping), utilizing subfraction of peripheral blood, algorithm reported as a rejection risk score

AlloMap, CareDx, Inc.

 

 

ICD-10 Diagnosis

 

 

All diagnoses

When services are Investigational and Not Medically Necessary:
For the procedure code listed above when criteria are not met.

When services are also Investigational and Not Medically Necessary:
For the procedure code listed below in all instances, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

CPT

 

0085T

Breath test for heart transplant rejection [Heartsbreath test]

 

 

ICD-10 Diagnosis

 

 

All diagnoses

References

Peer Reviewed Publications:

  1. Bernstein D, Williams GE, Eisen H, et al. Gene expression profiling distinguishes a molecular signature for grade 1B mild acute cellular rejection in cardiac allograft recipients. J Heart Lung Transplant. 2007; 26(12):1270-1280.
  2. Cadeiras M, Shahzad K, John MM, et al. Relationship between a validated molecular cardiac transplant rejection classifier and routine organ function parameters. Clin Transplant. 2010; 24(3):321-327.
  3. Cadeiras, M, von Bayern M, Sinha A, et al. Noninvasive diagnosis of acute cardiac allograft rejection. Curr Opin Organ Transplant. 2007; 12(5):543-550.
  4. Crespo-Leiro MG, Stypmann J, Schulz U, et al. Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients. BMC Cardiovasc Disord. 2015; 15:120.
  5. Crespo-Leiro MG, Stypmann J, Schulz U, et al. Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. Eur Heart J. 2016; 37(33):2591-2601.
  6. Crespo-Leiro MG, Zuckermann A, Bara C, et al. Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II). Transplantation. 2012; 94(11):1172-1177.
  7. Deng MC, Eisen HJ, Mehra MR, et al.; CARGO Investigators. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006; 6(1):150-160.
  8. Deng MC, Elashoff B, Pham MX, et al.; IMAGE Study Group. Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation. 2014; 97(6):708-714.
  9. Fang KC. Clinical utilities of peripheral blood gene expression profiling in the management of cardiac transplant patients. J Immunol. 2007: 4(3):209-217.
  10. Jarcho JA. Fear of rejection--monitoring the heart-transplant recipient. N Engl J Med. 2010; 362(20):1932-1933.
  11. Kobashigawa J, Patel J, Azarbal B, et al. Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial (EIMAGE). Circ Heart Fail. 2015; 8(3):557-564.
  12. Marboe CC, Lal PG, Chu K, et al. Distinctive peripheral blood gene expression profiles in patients forming nodular endocardial infiltrates (Quilty lesions) following heart transplantation. J Heart Lung Transplant. 2005;  24(2 suppl):S97.
  13. Mehra MR, Kobashigawa JA, Deng MC, et al.; CARGO Investigators. Transcriptional signals of T-cell and corticosteroid-sensitive genes are associated with future acute cellular rejection in cardiac allografts. J Heart Lung Transplant. 2007b; 26(12):1255-1263.
  14. Mehra MR, Kobashigawa JA, Deng MC, et al.; CARGO Investigators. Clinical implications and longitudinal alteration of peripheral blood transcriptional signals indicative of future cardiac allograft rejection. J Heart Lung Transplant. 2008; 27(3):297-301.
  15. Mehra MR, Uber PA. Genomic biomarkers and heart transplantation. Heart Fail Clin. 2007a; 3(1):83-86.
  16. Pham MX, Deng MC, Kfoury AG, et al. Molecular testing for long-term rejection surveillance in heart transplant recipients: design of the Invasive Monitoring Attenuation through Gene Expression (IMAGE) trial. J Heart Lung Transplant. 2007; 26(8):808-814.
  17. Pham MX, Teuteberg JJ, Kfoury AG, et al.; IMAGE Study Group. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010; 362(20):1890-1900.
  18. Phillips M, Boehmer JP, Cataneo RN, et al. Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study). J Am Coll Cardiol. 2002; 40(1):12-13.
  19. Phillips M, Boehmer JP, Cataneo RN, et al. Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study). J Heart Lung Transplant. 2004a; 23(6):701-708.
  20. Phillips M, Boehmer JP, Cataneo RN, et al. Prediction of heart transplant rejection with a breath test for markers of oxidative stress. Am J Cardiol. 2004b; 94(12):1593-1594.
  21. Sobotka PA, Gupta DK, Lansky DM, et al. Breath pentane is a marker of acute cardiac allograft rejection. J Heart Lung Transplant. 1994; 13(2):224-229.
  22. Starling RC, Pham M, Valantine H, et al.; Working Group on Molecular Testing in Cardiac Transplantation.  Molecular testing in the management of cardiac transplant recipients: initial clinical experience. J Heart Lung Transplant. 2006; 25(12):1389-1395.
  23. Strecker T, Rösch J, Weyand M, Agaimy A. Endomyocardial biopsy for monitoring heart transplant patients: 11-years-experience at a German heart center. Int J Clin Exp Pathol. 2013; 6(1):55-65.
  24. Yamani MH, Taylor DO, Haire C, et al. Post-transplant ischemic injury is associated with up-regulated AlloMap gene expression. Clin Transplant. 2007a; 21(4):523-525.
  25. Yamani MH, Taylor DO, Rodriguez ER, et al. Transplant vasculopathy is associated with increased AlloMap gene expression score. J Heart Lung Transplant. 2007b; 26(4):403-406.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Berry GJ, Burke MM, Andersen C, et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013; 32(12):1147-1162.
  2. Blue Cross Blue Shield Association. Gene Expression Profiling as a Noninvasive Method to Monitor for Cardiac Allograft Rejection. TEC Assessment, 2011; 26(8).
  3. CareDx. Outcomes AlloMap Registry: the Long-term Management and Outcomes of Heart Transplant Recipients With AlloMap Testing (OAR).  NLM Identifier: NCT01833195.  Last updated August 14, 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT01833195?term=AlloMap. Accessed on March 30, 2018.
  4. Centers for Medicare and Medicaid Services. National Coverage determination. Heartsbreath Test for Heart Transplant Rejection. NCD #260.10. December 8, 2008. Available at: http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=325&ncdver=1&DocID=260.10&from2=index_chapter_list.asp&list_type=&bc=gAAAAAgAAAAAAA%3d%3d&. Accessed on March 28, 2018.
  5. Costanzo MR, Dipchand A, Starling R. et al. The International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010; 29(8):914-956. Available at: http://www.jhltonline.org/article/S1053-2498(10)00358-X/abstract. Accessed on March 28, 2018.
  6. Francis GS, Greenberg BH, Hsu DT, et al. ACCF/AHA/ACP/HFSA/ISHLT 2010 clinical competence statement on management of patients with advanced heart failure and cardiac transplant: a report of the ACCF/AHA/ACP Task Force on Clinical Competence and Training. Circulation. 2010; 122(6):644-672. Available at: http://circ.ahajournals.org/content/122/6/644.full.pdf. Accessed on March 28, 2018.
  7. Society for Cardiovascular Pathology. International Society for Heart and Lung Transplantation (ISHLT) revised grading criteria. 2014.
  8. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005; 24(11):1710-1720.
  9. Taylor D, Meiser B, Webber, S, et al. The International Society of Heart and Lung Transplantation (ISHLT). Guidelines for the Care of Heart Transplant Recipients, Task Force 2: Immunosuppression and Rejection. 2010 Nov. 8; 1-41.
  10. Tice JA. California Technology Assessment Forum (CTAF). Gene expression profiling for the diagnosis of heart transplant rejection. A Technology Assessment.  San Francisco, CA: CTAF; October 13, 2010.
  11. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). New Humanitarian Device Approval. Heartsbreath No. H030004. Rockville, MD:FDA. February 24, 2004.  Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf3/h030004c.pdf. Accessed on March 28, 2018.
  12. U. S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). 510(k) Substantial Equivalence Determination Decision Summary for AlloMap® Molecular Expression Testing. No. K073482. Rockville, MD:FDA. Nov. 4, 2008. Available at: https://www.accessdata.fda.gov/cdrh_docs/reviews/k073482.pdf. Accessed on March 28, 2018.
  13. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. Humanitarian Use Device Exemptions. Available at:  http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/HDEApprovals/ucm161827.htm. Accessed on March 28, 2018.
  14. XDx, Inc. A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection Early Post-transplantation (EIMAGE). NLM Identifier: NCT00962377. Last updated December 20, 2010. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00962377?term=AlloMap&rank=1. Accessed on April 3, 2018.
  15. XDx, Inc. Cardiac Allograft Rejection Gene Expression Observational (CARGO) II STUDY (CARGOII). NLM Identifier: NCT00761787. Last updated March 9, 2009. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00761787?term=AlloMap&rank=2. Accessed on April 3, 2018.
  16. XDx, Inc. IMAGE: A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection. NLM Identifier: NCT00351559.  Last updated November 20, 2009. Available at:  http://www.clinicaltrials.gov/ct2/show/NCT00351559?term=00351559&rank=1. Accessed on April 3, 2018.
Index

AlloMap
Breath Test as an Aid for Diagnosis of Heart Transplant Rejection
Gene Expression Molecular Profiling
Heartsbreath

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. The document header wording was updated from “Current Effective Date” to “Publish Date.” References were updated.

Reviewed

05/04/2017

MPTAC review. The Rationale and References sections were updated.

Reviewed

05/05/2016

MPTAC review. References were updated.

 

01/01/2016

Updated Coding section with 01/01/2016 CPT changes; removed ICD-9 codes.

Reviewed

05/07/2015

MPTAC review. References were updated.

Reviewed

05/15/2014

MPTAC review. The Rationale and References were updated.

Reviewed

05/09/2013

MPTAC review. References were updated.

Reviewed

05/10/2012

MPTAC review. The Background and References were updated.

Revised

05/19/2011

MPTAC review. The position on AlloMap molecular expression testing has been changed to now consider medically necessary when criteria are met.  The Rationale, Background, Coding and Reference sections were updated.

Reviewed

05/13/2010

MPTAC review. The Background and Reference sections were updated.

Reviewed

05/21/2009

MPTAC review. Updated Reference section.

Reviewed

05/15/2008

MPTAC review. References were updated.

 

02/21/2008

The phrase "investigational/not medically necessary" was clarified to read "investigational and not medically necessary." This change was approved at the November 29, 2007 MPTAC meeting.

Reviewed

05/17/2007

MPTAC review. Reference section was updated.

Reviewed

06/08/2006

MPTAC review. References were updated and information was added about the CARGO Study of AlloMap testing.

Revised

07/14/2005

MPTAC review. AlloMap® molecular testing added as investigational/not medically necessary.

Revised

04/28/2005

MPTAC review.  Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.

Pre-Merger Organizations

Last Review Date

Document Number

Title

Anthem, Inc

 

 

No prior document

WellPoint Health Networks, Inc.

12/02/2004

2.04.32

Breath Test for Use as an Aid in the Diagnosis of Heart Transplant Rejection