After heart transplantation, individuals are monitored for cellular rejection by endomyocardial biopsies that are typically obtained from the right ventricle on a weekly basis for the first month, monthly for the following six months and yearly thereafter. Endomyocardial biopsy is invasive and carries a risk of adverse effects; therefore, non-invasive methods of detecting cellular rejection are being explored.
In heart transplant recipients, oxidative stress appears to accompany allograft rejection that degrades membrane polyunsaturated fatty acids and evolving alkanes and methylalkanes that are in turn excreted as volatile organic compounds in an individual’s breath. A laboratory test (e.g. Heartsbreath™) that measures breath markers of oxidative stress proposes to assist in the detection of heart transplant rejection.Another non-invasive approach has focused on patterns of gene expression as detected in the peripheral blood. The only commercially available test (AlloMap®) for heart transplant recipients involves measurement of a panel of genes derived from peripheral blood cells, and application of an algorithm to the results. The algorithm produces a single score with the lower scores indicating a lower risk of graft rejection.
The evaluation of genetic expression in the peripheral blood (e.g. Allomap®) for the monitoring of acute heart transplant rejection or heart transplant graft dysfunction is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
The measurement of volatile organic compounds by breath test to assist in the detection of heart transplant rejection is considered investigational.
The evaluation of genetic expression in the peripheral blood (e.g. Allomap®) for the monitoring of acute heart transplant rejection or heart transplant graft dysfunction is considered medically appropriate if ALL of the following are met:
Individual is 15 years of age or greater
Individual does not have a history of prior cardiac transplant rejection
Allograft function is stable with a low probability of acute cellular rejection
Individual is 55 days or greater since heart transplant
Individual is five years or less post heart transplant
Individual is not currently taking 20mg/day or more of prednisone or equivalent systemic corticosteroid
Individual has not received rejection therapy within the last 21 days
Individual has not received blood transfusion within the last 30 days
Any specific products referenced in this policy are just examples and are intended for illustrative purposes 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. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
There is insufficient evidence on the diagnostic accuracy of the Heartsbreath™ test, especially for grades 3 and 4 rejection, and no published studies have evaluated the clinical utility of this test. Gene expression testing (AlloMap®) can be used in place of endomyocardial biopsy to monitor stable individuals post-transplant. However, evidence is insufficient at this time for its use in predicting future allograft rejection.
AlloMap® (2014) The standard of care for the management of heart transplant patients: overview for health care professionals. Retrieved July 27, 2018 from www.caredxinc.com.
BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2017). Laboratory tests for heart transplant rejection. Retrieved July 27, 2018 from BlueWeb. (13 articles and/or guidelines reviewed)
Braga, J., Santos, I., McDonald, M., Shah, P., and Ross, H. (2012, March-April) Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies. Clinical Transplantation, 26 (2), 111-24. Abstract retrieved July 27, 2018 from PubMed database.
Centers for Medicare & Medicaid Services. CMS.gov. NCD for Heartsbreath test for heart transplant rejection (260.10). Retrieved November 4, 2015 from http://www.cms.gov.
Crespo-Leiro, M., Stypmann, J., Schulz, U., Zuckerman, A., Mohacsi, P, Bara, C., et al. (2015). Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients. BMC Cardiovascular Disorders, 15:120. (Level 2 evidence)
Crespo-Leiro, M., Stypmann, J., Schulz, U., Zuckerman, A., Mohacsi, P, Bara, C., et al. (2016). Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. European Heart Journal, 37, 2591-2601. (Level 3 evidence)
Deng, M., Elashoff, B., Pham, M., Teuteberg, J., Kfoury, A., Starling, R., et al. (2014). Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation, 97 (6), 708-714. (Level 4 evidence)
ECRI Institute. Emerging Technology Evidence Report. (2012, January). Gene expression profiling to monitor heart transplant rejection. Retrieved November 4, 2015 from ECRI Institute. (41 articles and/or guidelines reviewed)
eviCore healthcare. (2018, May). Clinical guidelines: lab management program. Retrieved July 27, 2018 from www.evicore.com.
International Society of Heart and Lung Transplantation. (2010) Guidelines for the care of heart transplant recipients. The Journal of Heart and Lung Transplantation, 29 (8), 914-956.
Kobashigawa, J., Patel, J., Azarbal, B., Kittleson, M., Chang, D., Czer, L. et. al. (2015) Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant. Circulation: Heart Failure, 8 (3), 557-564. (Level 2 evidence)
Mavrogeni, S., Athanasopoulos, G., Gouziouta, A., Leontiadis, E., Adamopoulos, S., and Kolovou, G. (2017, April) Cardiac transplantation: towards a new noninvasive approach of cardiac allograft rejection. Expert Reviews in Cardiovascular Therapy, 15 (4), 307-313. Abstract retrieved July 27, 2018 from PubMed database.
Pham, M., Teuteberg, J., Kfoury, A., Starling, R., Deng, M., Cappola, T., et al. (2010, May) Gene-expression profiling for rejection surveillance after cardiac transplantation. New England Journal of Medicine, 362 (20), 1880-1900. (Level 2 evidence)
U. S. Food and Drug Administration. (2004, February). Center for Devices and Radiological Health. Device Approvals and Clearances. Medical Devices. Heartsbreath - H030004. Retrieved March 10, 2011 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2008, August). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. AlloMap® Molecular Expression Testing - K073482. Retrieved March 10, 2011 from http://www.accessdata.fda.gov.
ORIGINAL EFFECTIVE DATE: 12/8/2007
MOST RECENT REVIEW DATE: 11/29/2018
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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