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. AlloMap® is an example of a commercially available molecular expression panel test that has been proposed to detect acute heart transplant rejection or the development of graft dysfunction. The test involves measurement of a panel of genes derived from peripheral blood cells, and applies an algorithm to the results. The algorithm produces a single score that considers the contribution of each gene in the panel. Lower scores indicate a lower risk of graft rejection.

POLICY

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.  The evidence supporting the AlloMap® test does not sufficiently determine the sensitivity and specificity of the test. Therefore, these laboratory tests remain investigational.

SOURCES

BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2016). Laboratory tests for heart transplant rejection. Retrieved September 2, 2016 from BlueWeb. (13 articles and/or guidelines reviewed)

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 4 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)

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. 2015;8:557-564. (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:  9/14/2017

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