BlueCross BlueShield of Tennessee Medical Policy Manual

Laboratory Tests for Heart Transplant Rejection

DESCRIPTION

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.

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION

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.

SOURCES  

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

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