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 6 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 breath. The Heartsbreath test is an example of a commercially available noninvasive test that measures breath markers of oxidative stress that has been developed to assist in the detection of heart transplant rejection. The Heartsbreath test analyzes the breath methylated alkane contour (BMAC), which is derived from the abundance of C4-C20 alkanes and monomethylalkanes and has been identified as a marker to detect grade 3 (significant) heart transplant rejection.
Another non-invasive approach has focused on patterns of gene expression of immunomodulatory cells as detected in the peripheral blood. For example, microarray technology permits the analysis of the gene expression of thousands of genes, including those with functions that are known or unknown. Patterns of gene expression can then be correlated with known clinical conditions, permitting a selection of a finite number of genes to compose a custom multi-gene test panel, which then can be evaluated using polymerase chain reaction (PCR) techniques. AlloMap™ is an example of a commercially available molecular expression test that has been developed to detect acute heart transplant rejection or the development of graft dysfunction. The test involves PCR expression 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
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, including, but not limited to the detection of acute heart transplant rejection or graft dysfunction is considered investigational.
IMPORTANT REMINDER
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.
ADDITIONAL INFORMATION
Breath Test (e.g., Heartsbreath test)
The Heartsbreath test received approval from the U.S. Food and Drug Administration (FDA) through a humanitarian device exemption in February 2004.
How this test can be integrated into the management of the individual, either to select or deselect individuals for endomyocardial biopsy, or potentially replace endomyocardial biopsy altogether is not known. Therefore, the impact of this test on management decisions and health outcomes is unknown.
Peripheral Blood Test (e.g., AlloMap™)
Additional clinical experience is needed to confirm and extend the current results, and to address several important questions such as the best cutoff value and when to test. In addition, the impact of this test on management decisions and health outcomes is unknown.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2010). Laboratory tests for heart transplant rejection (2.01.68). Retrieved March 10, 2011 from BlueWeb. (12 articles and/or guidelines reviewed)
Complete Guide to Medicare Coverage Issues [Computer software]. (2010, April). Heartsbreath test for heart transplant rejection (NCD 260.10, p. 2-202). The Ingenix.
Deng, M. C., Eisen, H. J., Mehra, M. R., Billingham, M., Marboe, C. C., Berry, G., et al. (2006). Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. American Journal of Transplantation, 6 (1), 150-160.
ECRI Institute. Health Technology Information Service. Emerging Technology (TARGET) Evidence Report. (2009, April). Gene expression profiling to monitor acute heart transplant rejection. Retrieved March 10, 2011 from ECRI Institute. (21 articles and/or guidelines reviewed)
International Society of Heart and Lung Transplantation. (2010). ISHLT guidelines for the care of heart transplant recipients. Retrieved March 10, 2011 from https://www.ishlt.org/ContentDocuments/ISHLT_GL_TaskForce2_110810.pdf.
Pham, M., Teutenberg, J., Kfoury, A., Starling, R., Deng, M., Cappola, T., et al. (2010) Gene-expresing profiling rejection surveillance after cardiac transplantation. New England Journal of Medicaine, 362 (20), 1890-1900. (Level 1 Evidence - Industry Sponsored)
Phillips, M., Boehmer, J. P., Cataneo, R. N., Cheema, T., Eisen, H. J., Fallon, J. T., et al. (2004). Heart allograft rejection: Detection with breath alkanes in low levels (the HARDBALL study). The Journal of Heart and Lung Transplant, 23 (6), 701-708. (Level 1 Evidence - Industry sponsored)
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/cdrh_docs/pdf3/H030004b.pdf.
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/cdrh_docs/reviews/K073482.pdf.
MOST RECENT REVIEW DATE: 6/9/2011
ID_BA
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.
This document has been classified as public information.