BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Dilated Cardiomyopathy

DESCRIPTION

Dilated cardiomyopathy (DCM) is a disorder of cardiac muscle that leads to progressive left ventricular enlargement and dilation in conjunction with significant systolic dysfunction. The clinical manifestations of DCM are heart failure, and/or cardiac arrhythmias. There are a variety of causes of DCM, which include genetic and nongenetic conditions. The diagnosis of DCM requires the presence of left ventricular enlargement and evidence of systolic dysfunction.

When an individual presents with DCM, a work-up is performed to identify underlying causes. In many cases, a definite underlying cause is not identified. This has traditionally been termed idiopathic dilated cardiomyopathy. Familial DCM is diagnosed when two closely related family members have DCM in the absence of underlying causes. Penetrance of familial DCM is variable and age dependent. Treatment of DCM includes medications to reduce fluid overload and relieve strain on the heart and lifestyle modifications such as salt restriction. If a clinically significant arrhythmia is present, it may also require treatment.

Genetic forms of DCM are heterogeneous in the types of genetic variant, clinical expression, and hereditability. Genetic variations on more than 40 different genes have been associated with DCM. Because of the large number of potential variations associated with DCM and the infrequent nature of most variants, panel testing is frequently proposed although test yield has not been demonstrably higher when large scale testing is used versus disease specific panels.

Examples of commercially available genetic panels for DCM include:

Laboratory	Panel Name	Number of Genes Tested
Ambry Genetics	DCM panel	37
GeneDX	DCM/Left Ventricular Non-Compaction Panel Cardiomyopathies Del/Dup Panel Cardiomyopathy Panel	61 20 91
Precipio	DCM panel Conduction disease-DCM Panel	13 2
Partners Healthcare	DCM panel/Arrhythmogenic Cardiomyopathy Panel	27

POLICY

Genetic testing for dilated cardiomyopathy is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

MEDICAL APPROPRIATENESS

Genetic testing for dilated cardiomyopathy is considered medically appropriate if ALL of the following are met:
- No previous genetic testing for dilated cardiomyopathy
- Targeted testing includes one or more of the following genes:
- - TTN
  - TNNT2
  - MYH7
  - MYH6
  - SCN5A
  - MYBPC3
  - LMNA
- Testing is indicated for ANY ONE of the following:
- - Predictive testing for asymptomatic individual when known disease-causing mutation in a dilated cardiomyopathy gene has been identified in first or second- degree relative(s)
  - Diagnostic testing for a symptomatic individual if ANY ONE of the following criteria are met:
  - - Individual with confirmed diagnosis of dilated cardiomyopathy if ALL the following criteria are met:
    - - No evidence of specific syndrome in individual or family (e.g., muscular dystrophies, Friedreich’s ataxia, atypical Werner syndrome, Dunnigan-type familial partial lipodystrophy)
      - Non-genetic causes have been ruled out (e.g., infection, toxin exposures, metabolic disease, autoimmune disease, tachyarrhythmia, sarcoidosis, and coronary artery disease)
    - Individual with a family history of idiopathic dilated cardiomyopathy if ANY ONE of the following criteria are met:
    - - A diagnosis of idiopathic dilated cardiomyopathy with one or more first or second-degree relatives with diagnosis of idiopathic dilated cardiomyopathy or peripartum cardiomyopathy
      - A diagnosis of idiopathic dilated cardiomyopathy with a suspicious family history that includes a first or second degree relative with sudden adult death or young cardiac or thromboembolic event
      - Mildly affected individual (dilated left ventricle but normal ejection fraction) with first or second degree relative with a known diagnosis of idiopathic dilated cardiomyopathy

IMPORTANT REMINDERS

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 or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

ADDITIONAL INFORMATION

Genetic testing for dilated cardiomyopathy may result in changes in management to include earlier implantation of cardiac defibrillators or increased surveillance to detect worsening of symptoms. The evidence is sufficient to determine that the technology results is a meaningful improvement in the net health outcome.

SOURCES

Bozkurt, B., Colvin, M., Cook, J., Cooper, L. T., Deswal, A., Fonarow, G. C., et al (2016). Current diagnostic and treatment strategies for specific dilated cardiomyopathies: A scientific statement from the American Heart Association. Circulation, 134 (23), e579–e646. (Level 2 evidence)

Burke, M., Cook, S., Seidman, J., & Seidman, C. (2016). Clinical and mechanistic insights into the genetics of cardiomyopathy. Journal of American College of Cardiology, 68 (25), 2871-2886. (Level 2 evidence)

Collaborative Research Group of the European Human and Capital Mobility. (1999). Guidelines for the study of familial dilated cardiomyopathies. European Heart Journal. Retrieved January 10, 2022 from https://academic.oup.com/eurheartj.

eviCore healthcare. (2023, January). Dilated cardiomyopathy genetic testing guidelines. Retrieved January 24, 2023 from www.evicore.com. (17 articles and/or guidelines reviewed)

Grünig, E., Tasman, J. A., Kücherer, H., Franz, W., Kübler, W., & Katus, H. A. (1998). Frequency and phenotypes of familial dilated cardiomyopathy. Journal of the American College of Cardiology, 31 (1), 186–194. (Level 4 evidence)

Haas, J., Frese, K. S., Peil, B., Kloos, W., Keller, A., Nietsch, R., et al. (2015). Atlas of the clinical genetics of human dilated cardiomyopathy. European Heart Journal, 36 (18), 1123–35a. Abstract retrieved January 6, 2022 from PubMed database.

Heart Failure Society of America. (2018). Genetic evaluation of cardiomyopathy – a Heart Failure Society of America practice guideline. Journal of Cardiac Failure, 24 (5), 281-302. Retrieved January 10, 2022 from https://hfsa.org/.

Heart Rhythm Society (HRS) and European Heart Rhythm Association (EHRA). (2011). HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Europace. Retrieved on January 11, 2022 from https://academic.oup.com/europace.

Hershberger, R. E., & Jordan, E. (2007, updated July 2021). Dilated cardiomyopathy overview. In M. P. Adam (Eds.) et. al., GeneReviews®.University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/.

Hershberger, R. E., Givertz, M. M., Ho, C. Y., Judge, D. P., Kantor, P. F., McBride, K. L., Morales, A., Taylor, M., Vatta, M., & Ware, S. M. (2018). Genetic evaluation of cardiomyopathy - a Heart Failure Society of America practice guideline. Journal of Cardiac Failure, 24 (5), 281–302. Abstract retrieved January 11, 2022 from PubMed database.

Hershberger, R.E., & Siegfried, J.D. (2011). Update 2011: Clinical and genetic issues in familial dilated cardiomyopathy. Journal of the American College of Cardiology, 57 (16), 1641-1649. (Level 3 evidence)

Hershberger, R.E., Givertz, M.M., Ho, C.Y., Judge, D.P., Kantor, P.F., McBride, K.L., et al. (2018). Genetic evaluation of cardiomyopathy: A clinical practice resource of the American college of medical genetics and genomics (ACMG). Genetics in Medicine: Official Journal of The American College of Medical Genetics, 20 (9), 899-909. (Level 3 evidence)

Japp, A. G., Gulati, A., Cook, S. A., Cowie, M. R., & Prasad, S. K. (2016). The diagnosis and evaluation of dilated cardiomyopathy. Journal of the American College of Cardiology, 67 (25), 2996–3010. (Level 5 evidence)

National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand. (2018). National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Guidelines for the prevention, detection, and management of heart failure in Australia 2018. Retrieved January 10, 2022 from www.heartfoundation.org.au.

Ouellette, A. C., Mathew, J., Manickaraj, A. K., Manase, G., Zahavich, L., Wilson, J., et al. (2018). Clinical genetic testing in pediatric cardiomyopathy: Is bigger better? Clinical Genetics, 93 (1), 33–40. (Level 4 evidence)

Peters, S., Kumar, S., Elliott, P., Kalman, J. M., & Fatkin, D. (2019). Arrhythmic genotypes in familial dilated cardiomyopathy: Implications for genetic testing and clinical management. Heart, Lung & Circulation, 28 (1), 31–38. (Level 5 evidence)

Taylor, M. R., Carniel, E., & Mestroni, L. (2006). Cardiomyopathy, familial dilated. Orphanet Journal of Rare Diseases, 1, 27. (Level 5 evidence)

Wexler, R. K., Elton, T., Pleister, A., & Feldman, D. (2009). Cardiomyopathy: An overview. American Family Physician, 79 (9), 778–784. (Level 5 evidence)

Wilsbacher L. D. (2020). Clinical implications of the genetic architecture of dilated cardiomyopathy. Current Cardiology Reports, 22 (12), 170. (Level 5 evidence)

ORIGINAL EFFECTIVE DATE: 7/12/2014

MOST RECENT REVIEW DATE: 3/9/2023

ID_EC

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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