MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
Original Issue Date (Created):
11/1/2012
Most Recent Review Date (Revised):
7/26/2016
Effective Date:
1/1/2017
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
Genetic testing for predisposition to hypertrophic cardiomyopathy (HCM) may be considered
medically necessary for individuals who are at risk for development of HCM, defined as
having a first-degree relative with established HCM, when there is a known pathogenic gene
mutation present in that affected relative (See Policy Guidelines Section).
Genetic testing for predisposition to HCM is considered not medically necessary for patients
with a family history of HCM in which a first-degree relative has tested negative for pathologic
mutations.
Genetic testing for predisposition to HCM is considered investigational for all other patient
populations, including but not limited to individuals who have a first-degree relative with
clinical HCM, but in whom genetic testing is unavailable. There is insufficient evidence to
support a conclusion concerning the health outcomes or benefits associated with this procedure.
POLICY GUIDELINES
Due to the complexity of genetic testing for hypertrophic cardiomyopathy (HCM) and the
potential for misinterpretation of results, the decision to test and the interpretation of test results
should be performed by, or in consultation with, an expert in the area of medical genetics and/or
HCM.
To inform and direct genetic testing for at-risk individuals, genetic testing should initially be
performed in at least 1 close relative with definite HCM (index case), if possible. See Benefit
Application section for information regarding testing of the index case.
Because there are varying degrees of penetrance for different HCM mutations, consideration for
testing of second- or third-degree relatives may be appropriate in certain circumstances. Some
judgment should be allowed for these decisions, for example, in the case of a small family
pedigree. Consultation with an expert in medical genetics and/or the genetics of HCM, in
Page 1
MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
conjunction with a detailed pedigree analysis, is appropriate when testing of second- or thirddegree relatives is considered.
II. PRODUCT VARIATIONS
TOP
This policy is applicable to all programs and products administered by Capital BlueCross unless
otherwise indicated below.
FEP PPO*
*Genetic screening/testing related to family history of cancer or other disease is not covered
except for BRCA testing/screening. The FEP Medical Policy manual can be found at:
www.fepblue.org
III. DESCRIPTION/BACKGROUND
TOP
Familial hypertrophic cardiomyopathy (HCM) is an inherited condition that is caused by a
mutation in one or more of the cardiac sarcomere genes. HCM is associated with numerous
cardiac abnormalities, the most serious of which is sudden cardiac death (SCD). Genetic testing
for HCM-associated mutations is currently available through a number of commercial
laboratories.
Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular
condition, with a phenotypic prevalence of approximately 1 in 500 adults (0.2%). (1) It is the
most common cause of sudden cardiac death (SCD) in adults younger than 35 years of age and is
probably also the most the most common cause of death in young athletes. (2) The overall death
rate for patients with HCM is estimated to be 1% per year in the adult population. (3,4)
The genetic basis for HCM is a defect in the cardiac sarcomere, which is the basic contractile
unit of cardiac myocytes composed of a number of different protein structures. (5) Nearly 1,000
individual mutations in at least 14 different genes have been identified to date. (6,8)
Approximately 90% of pathogenic mutations are missense (ie, 1 amino acid is replaced for
another), and the strongest evidence for pathogenicity is available for 11 genes coding for thick
filament proteins (MYH7, MYL2, MYL3), thin filament proteins (TNNT2, TNNI3, TNNC1, TPM1,
ACTC), intermediate filament proteins (MYBPC3), and the Z-disc adjoining the sarcomere
(ACTN2, MYOZ2). Mutations in myosin heavy chain (MYH7) and myosin-binding protein C
(MYBPC3) are the most common and account for roughly 80% of sarcomeric HCM. These
genetic defects are inherited in an autosomal dominant pattern with rare exceptions.(5) In
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
patients with clinically documented HCM, genetic abnormalities can be identified in
approximately 0%.7,9 Most patients with clinically documented disease are demonstrated to
have a familial pattern, although some exceptions are found presumably due to de novo
mutations.(9)These genetic defects are inherited in an autosomal dominant pattern with rare
exceptions. In patients with clinically documented HCM, genetic abnormalities can be identified
in approximately 60%. (7,9) Most patients with clinically documented disease are demonstrated
to have a familial pattern, although some exceptions are found presumably due to de novo
mutations.
The clinical diagnosis of HCM depends on the presence of left ventricular hypertrophy (LVH),
measured by echocardiography or magnetic resonance imaging (MRI), in the absence of other
known causative factors such as valvular disease, long-standing hypertension, or other
myocardial disease.(7) In addition to primary cardiac disorders, there are systemic diseases that
can lead to LVH and thus “mimic” HCM. These include infiltrative diseases such as
amyloidosis, glycogen storage diseases such as Fabry disease and Pompe disease, and
neuromuscular disorders such as Noonan’s syndrome and Friederich’s ataxia. These disorders
need to be excluded before a diagnosis of familial HCM is made.
HCM is a very heterogenous disorder. Manifestations range from subclinical, asymptomatic
disease to severe life-threatening disease. Wide phenotypic variability exists among individuals,
even when an identical mutation is present, including among affected family members.(2) This
variability in clinical expression may be related to environmental factors and modifier genes.
(10) A large percentage of patients with HCM, perhaps the majority of all HCM patients, are
asymptomatic or have minimal symptoms. (9,10)These patients do not require treatment and are
not generally at high risk for SCD. A subset of patients has severe disease that causes a major
impact on quality of life and life expectancy. Severe disease can lead to disabling symptoms, as
well as complications of HCM, including heart failure and malignant ventricular arrhythmias.
Symptoms and presentation may include SCD due to unpredictable ventricular
tachyarrhythmias, heart failure, or atrial fibrillation, or some combination.(11) Management of
patients with HCM involves treating cardiac comorbidities, avoiding therapies that may worsen
obstructive symptoms, treating obstructive symptoms with β-blockers, calcium channel blockers,
and (if symptoms persist), invasive therapy with surgical myectomy or alcohol ablation,
optimizing treatment for heart failure, if present, and SCD risk stratification.
Diagnostic screening of first-degree relatives and other family members is an important
component of HCM management. Guidelines have been established for clinically unaffected
relatives of affected individuals. Screening with physical examination, electrocardiography, and
echocardiography is recommended every 12-18 months for individuals between the ages of 12
to 18 years and every 3 to 5 years for adults. Additional screening is recommended for any
change in symptoms that might indicate the development of HCM (10).
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
Genetic Testing for Familial Hypertrophic Cardiomyopathy
Genetic testing has been proposed as a component of screening at-risk individuals to determine
predisposition to HCM among those patients at risk. Patients at risk for HCM are defined as
individuals who have a close family member with established HCM. Results of genetic testing
may influence management of at-risk individuals, which may in turn lead to improved outcomes.
Furthermore, results of genetic testing may have implications for decision making in the areas of
reproduction, employment, and leisure activities.
Commercial testing has been available since May 2003, and there are numerous commercial
companies that currently offer genetic testing for HCM.(6,12-15) Testing is performed either as
comprehensive testing or targeted gene testing. Comprehensive testing, which is done for an
individual without a known genetic mutation in the family, analyzes the genes that are most
commonly associated with genetic mutations for HCM and evaluates whether any potentially
pathogenic mutations are present. The number of HCM genes in the testing panel ranges between
12 and 18, and additional testing characteristics of some of the commercially available panels are
presented in Table 1.6 For a patient with a known mutation in the family, targeted testing is
performed. Targeted mutation testing evaluates the presence or absence of a single mutation
known to exist in a close relative.
There can be difficulties in determining the pathogenicity of genetic variants associated with
HCM. Some studies have reported that assignment of pathogenicity has a relatively high error
rate and that classification changes over time,(16,17) With next-generation (NGS) and wholeexome sequencing techniques, the sensitivity of identifying variants on the specified genes has
increased substantially. At the same time, the number of variants of unknown significance is also
increased with NGS. Also, the percent of individuals who have more than 1 mutation that is
thought to be pathogenic is increasing. A study in 2013 reported that 9.5% (19/200) patients
from China with HCM had multiple pathogenic mutations and that the number of mutations
correlated with severity of disease.18
Table 1. Characteristics of Commercial Testing for HCM
Company
GeneDx (Gaithersburg,
MD)
Transgenomic
(Omaha, NE)
Correlagen Diagnostics
(Waltham, MA)
Partners (Cambridge,
MA)
ApolloGen (Irvine, CA)
Prevention Genetics
(Marshfield, WI)
No. of HCM
Genes in Panel
18
Next-generation sequencing
12
Direct (Sanger) sequencing
18
Direct (Sanger) sequencing
18
Next-generation and Sanger
sequencing
Next-generation sequencing
Next-generation sequencing
and Sanger sequencing
18
15
Testing Technique
Turnaround
Time, wk
8-10
No. of Probability
Categories
5
4-6
(comprehensive)
2-4 (targeted)
6-8
3
5
5
5-6
5-7
3
4
7
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
Invitae (San Francisco,
CA)
16
Next-generation sequencing
and deletion/duplication/
copy number variant
analysis
Adapted from Maron et al6 and GeneTests.org.
NS
2-3
Some of these panels include testing for multisystem storage diseases that may include cardiac
hypertrophy, such as Fabry disease (GLA), familial transthyretin amyloidosis (TTR), X-linked
Danon disease (LAMP2). Several academic centers, including Emory University School of
Medicine and Washington University in St. Louis, also offer HCM genetic panels.
Other panels include testing for genes that are related to HCM but also those associated with
other cardiac disorders. For example, the Comprehensive Cardiomyopathy panel (ApolloGen,
Irvine, CA) is a next-generation sequencing panel of 44 genes that are associated with HCM,
dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular
cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia, left ventricular
noncompaction syndrome, Danon syndrome, Fabry disease, Barth syndrome, and transthyretin
amyloidosis.
Regulatory Status
Clinical laboratories may develop and validate tests in-house and market them as a laboratory
service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the
Clinical Laboratory Improvement Act (CLIA). Sequencing tests for hypertrophic
cardiomyopathy (HCM) are available under the auspices of CLIA. Laboratories that offer LDTs
must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug
Administration (FDA) has chosen not to require any regulatory review of this test.
There are no assay kits approved by FDA for genetic testing for HCM.
IV. RATIONALE
TOP
This evidence review was created in December 2011 and has been updated periodically with
literature review.
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
Table 2. Summary of Key Trials
NCTNo.
Ongoing
NCT01736566
Trial Name
The MedSeg
Project Pilot Study: Integrating Whole Genome
Sequencing Into the Practice of Clinical Medicine
HCMR - Novel Markers of Prognosis in Hypertrophic
NCT01915615
Cardiomyopathy
NCT00156429
Genetic Predictors of Outcome in HCM Patients
NCT: national clinical trial.
Planned
Enrollment
Completion
Date
200
Nov 2015
2750
Nov 201 8
540
May 2020
Summary of Evidence
The evidence for testing for specific hypertrophic cardiomyopathy (HCM)‒related mutation
identified in affected family member(s) in individuals who are asymptomatic with risk for HCM
because of a positive family history includes studies reporting on the analytic and clinical
validity of testing. Relevant outcomes include overall survival, test accuracy and validity,
changes in reproductive decision making, symptoms, and morbid events. For individuals at risk
for HCM (first-degree relatives), genetic testing is most useful when there is a known mutation
in the family. In this situation, genetic testing will establish the presence or absence of the same
mutation in a close relative with a high degree of certainty. Absence of this mutation will
establish that the individual has not inherited the familial predisposition to HCM and thus has a
similar risk of developing HCM as the general population. These patients no longer need
ongoing surveillance for the presence of clinical signs of HCM. Although no direct evidence
comparing outcomes for at-risk individuals managed with and without genetic testing was
identified, there is a strong indirect chain of evidence that there are management changes that
improve outcomes with genetic testing when there is a known familial mutation. The evidence is
sufficient to determine qualitatively that the technology results in a meaningful improvement in
the net health outcome.
The evidence for nonspecific testing for HCM-related mutation(s) in individuals who are
asymptomatic with risk for HCM because of a positive family history includes studies reporting
on the analytic and clinical validity of testing. Relevant outcomes include overall survival, test
accuracy and validity, changes in reproductive decision making, symptoms, and morbid events.
Given the wide genetic variation in HCM and the likelihood that not all causative mutations have
been identified, there is imperfect clinical sensitivity. Therefore, a negative test is not sufficient
to rule out a mutation in patients without a known family mutation. On the other hand, variability
in clinical penetrance means that a positive genetic test does not always “rule in” clinical HCM.
For at-risk individuals without a known mutation in the family, the evidence does not permit
conclusions of the effect of genetic testing on outcomes, since there is not a clear relationship
between testing and improved outcomes. The evidence is insufficient to determine the effects of
the technology on health outcomes.
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
SUPPLEMENTAL INFORMATION
Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate
with and make recommendations during this process, through the provision of appropriate
reviewers, input received does not represent an endorsement or position statement by the
physician specialty societies or academic medical centers, unless otherwise noted.
Clinical input was solicited in January 2011 on general agreement with the policy. This was
followed up by a second round of focused clinical vetting in October 2011 to address specific
questions raised after the first round of vetting. The initial vetting indicated uniform agreement
with the medically necessary indication for individuals with a first-degree relative who has a
known pathologic mutation. This vetting also asked whether testing should be restricted to firstdegree relatives. For this question, there was a mixed response, with 2 reviewers indicating that
they agree with testing only first-degree relatives, two reviewers indicating that testing should be
offered to non-first-degree relatives, and 1 reviewer who was unsure.
The second round of clinical vetting focused on the changes in management that could result
from genetic testing. Reviewers were uniform in responding that a positive test will result in
heightened surveillance. All but 1 reviewer indicated that a negative test will eliminate the need
for future surveillance in all cases. There was general agreement that the surveillance schedule
used in clinical practice was that proposed by Maron et al.10
Practice Guidelines and Position Statements
European Society of Cardiology
In 2014, the European Society of Cardiology issued guidelines on the diagnosis and management
of HCM, which included the following recommendations related to genetic testing51:
Class I Recommendations
 Genetic counselling is recommended for all patients with HCM when their disease cannot
be explained solely by a non-genetic cause, whether or not clinical or genetic testing will
be used to screen family members. (Level of Evidence: B)
 Genetic testing is recommended in patients fulfilling diagnostic criteria for HCM, when it
enables cascade genetic screening of their relatives. (Level of Evidence: B)
 It is recommended that genetic testing be performed in certified diagnostic laboratories
with expertise in the interpretation of cardiomyopathy-related mutations. (Level of
Evidence: C)
 In the presence of symptoms and signs of disease suggestive of specific causes of HCM,
genetic testing is recommended to confirm the diagnosis. (Level of Evidence: B)
 Cascade genetic screening, after pre-test counselling, is recommended in first-degree
adult relatives of patients with a definite disease-causing mutation. (Level of Evidence: B)
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POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248

Clinical evaluation, employing ECG and echocardiography and long-term follow-up, is
recommended in first-degree relatives who have the same definite disease-causing
mutation as the proband. (Level of Evidence: C)
Class IIa Recommendations
 Genetic counselling should be performed by professionals trained for this specific task
working within a multidisciplinary specialist team. (Level of Evidence: C)
 Genetic testing in patients with a borderline diagnosis of HCM should be performed only
after detailed assessment by specialist teams. (Level of Evidence: C)
 Post-mortem genetic analysis of stored tissue or DNA should be considered in deceased
patients with pathologically confirmed HCM, to enable cascade genetic screening of their
relatives. (Level of Evidence: C)
 First-degree relatives who do not have the same definite disease-causing mutation as the
proband should be discharged from further follow-up but advised to seek re-assessment if
they develop symptoms or when new clinically relevant data emerge in the family. (Level
of Evidence: B)
 When no definite genetic mutation is identified in the proband or genetic testing is not
performed, clinical evaluation with ECG and echocardiography should be considered in
first-degree adult relatives and repeated every 2–5 years (or 6–12 monthly if nondiagnostic abnormalities are present). (Level of Evidence: C)
 The children of patients with a definite disease-causing mutation should be considered for
predictive genetic testing—following pre-test family counselling—when they are aged 10
or more years and this should be carried out in accordance with international guidelines
for genetic testing in children. (Level of Evidence: C)
 In first-degree child relatives aged 10 or more years, in whom the genetic status is
unknown, clinical assessment with ECG and echocardiography should be considered
every 1–2 years between 10 and 20 years of age, and then every 2–5 years thereafter.
(Level of Evidence: C)
Class IIb Recommendations
If requested by the parent(s) or legal representative(s), clinical assessment with ECG and
echocardiography may precede or be substituted for genetic evaluation after counselling
by experienced physicians and when it is agreed to be in the best interests of the child.
(Level of Evidence: C)
When there is a malignant family history in childhood or early-onset disease or when
children have cardiac symptoms or are involved in particularly demanding physical
activity, clinical or genetic testing of first-degree child relatives before the age of 10
years may be considered. (Level of Evidence: C)
In definite mutation carriers who have no evidence of disease expression, sports activity may
be allowed after taking into account the underlying mutation and the type of sport
activity, and the results of regular and repeated cardiac examinations. (Level of Evidence:
C)
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
American College of Cardiology Foundation and the American Heart Association
The American College of Cardiology Foundation and the American Heart Association issued
joint guidelines on the diagnosis and treatment of hypertrophic cardiomyopathy in 2011.11 The
following recommendations were issued concerning genetic testing.
Class I Recommendations
Evaluation of familial inheritance and genetic counseling is recommended as part of the
assessment of patients with HCM (Level of Evidence: B)
Patients who undergo genetic testing should also undergo counseling by someone
knowledgeable in the genetics of cardiovascular disease so that results and their clinical
significance can be appropriately reviewed with the patient (Level of Evidence: B)
Screening (clinical, with or without genetic testing) is recommended in first-degree relatives
of patients with HCM (Level of Evidence: B)
Genetic testing for HCM and other genetic causes of unexplained cardiac hypertrophy is
recommended in patients with an atypical clinical presentation of HCM or when another
genetic condition is suspected to be the cause (Level of Evidence: B)
Class IIa Recommendations
Genetic testing is reasonable in the index patient to facilitate the identification of first-degree
family members at risk for developing HCM (Level of Evidence: B)
Class IIb Recommendations
The usefulness of genetic testing in the assessment of risk of SCD in HCM is uncertain
(Level of Evidence: B)
Class III Indications: No Benefit
Genetic testing is not indicated in relatives when the index patient does not have a definitive
pathogenic mutation (Level of Evidence: B)
Ongoing clinical screening is not indicated in genotype-negative relatives in families with
HCM (Level of Evidence: B)
Heart Rhythm Society and the European Heart Rhythm Association
The Heart Rhythm Society and the European Heart Rhythm Association published
recommendations for genetic testing for cardiac channelopathies and cardiomyopathies in
2011.52 For hypertrophic cardiomyopathy, the following recommendations were made:
Comprehensive or targeted HCM genetic testing is recommended for any patient in whom a
cardiologist has established a clinical diagnosis of HCM based on examination of the
patient’s clinical history, family history, and electrocardiographic/echocardiographic
phenotype
Mutation-specific testing is recommended for family members and appropriate relatives
following the identification of the HCM-causative mutation in an index case.
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force has not addressed genetic testing for hypertrophic
cardiomyopathy.
Medicare National Coverage
There is no national coverage determination (NCD).
V. DEFINITIONS
TOP
FIRST DEGREE RELATIVE- refers to parent, sibling or child.
SECOND DEGREE RELATIVE- refers to an aunt, uncle, niece, nephew, or grandparent.
THIRD DEGREE RELATIVE- refers to a great aunt/uncle, first cousin, or great
grandmother/grandfather.
VI. BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit under
the member's contract. Benefit determinations should be based in all cases on the applicable
contract language. Medical policies do not constitute a description of benefits. A member’s
individual or group customer benefits govern which services are covered, which are excluded,
and which are subject to benefit limits and which require preauthorization. Members and
providers should consult the member’s benefit information or contact Capital for benefit
information.
VII. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical
advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of
members. Members should discuss any medical policy related to their coverage or condition with their provider
and consult their benefit information to determine if the service is covered. If there is a discrepancy between this
medical policy and a member’s benefit information, the benefit information will govern. Capital considers the
information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.
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MEDICAL POLICY
POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
VIII. CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined by the
terms of member benefit information. In addition, not all covered services are eligible for separate
reimbursement.
Covered when medically necessary:
CPT
Codes ®
81405
81406
81407
81439
81479
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved .
HCPCS
Code
Description
S3865
Comprehensive gene sequence analysis for hypertrophic cardiomyopathy
S3866
Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM)
in an individual with a known HCM mutation in the family
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
ICD-10-CM
Diagnosis
Codes:
I42.1
I42.2
Z13.71
Z31.430
Z31.431
Z82.41
Z82.49
Description
Obstructive hypertrophic cardiomyopathy
Other hypertrophic cardiomyopathy
Encounter for nonprocreative screening for genetic disease carrier status
Encounter of female for testing for genetic disease carrier status for procreative
management
Encounter of male for testing for genetic disease carrier status for procreative
management
Family history of sudden cardiac death
Family history of ischemic heart disease and other diseases of the circulatory system
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
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POLICY TITLE
GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
IX. REFERENCES
TOP
1. Ramaraj R. Hypertrophic cardiomyopathy: etiology, diagnosis, and treatment. Cardiol Rev.
Jul-Aug 2008;16(4):172-180. PMID 18562807
2. Alcalai R, Seidman JG, Seidman CE. Genetic basis of hypertrophic cardiomyopathy: from
bench to the clinics. J Cardiovasc Electrophysiol. Jan 2008;19(1):104-110. PMID 17916152
3. Marian AJ. Genetic determinants of cardiac hypertrophy. Curr Opin Cardiol. May
2008;23(3):199-205. PMID 18382207
4. Roberts R, Sigwart U. Current concepts of the pathogenesis and treatment of hypertrophic
cardiomyopathy. Circulation. Jul 12 2005;112(2):293-296. PMID 16009810
5. Keren A, Syrris P, McKenna WJ. Hypertrophic cardiomyopathy: the genetic determinants of
clinical disease expression. Nat Clin Pract Cardiovasc Med. Mar 2008;5(3):158-168. PMID
18227814
6. Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20
years: clinical perspectives. J Am Coll Cardiol. Aug 21 2012;60(8):705-715. PMID
22796258
7. Cirino AL HC. Hypertrophic Cardiomyopathy: the genetic determinants of clinical disease
expression. GeneReviews 2008;
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hyper-card. Accessed
1/18/2009, 2009.
8. Ghosh N, Haddad H. Recent progress in the genetics of cardiomyopathy and its role in the
clinical evaluation of patients with cardiomyopathy. Curr Opin Cardiol. Mar
2011;26(2):155-164. PMID 21297463
9. Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet. Jun 5 2004;363(9424):18811891. PMID 15183628
10. Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European
Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy.
A report of the American College of Cardiology Foundation Task Force on Clinical Expert
Consensus Documents and the European Society of Cardiology Committee for Practice
Guidelines. J Am Coll Cardiol. Nov 5 2003;42(9):1687-1713. PMID 14607462
11. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA Guideline for the Diagnosis and
Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of
Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation. Nov 8 2011;124(24):2761-2796. PMID 22068434
12. Arya A, Bode K, Piorkowski C, et al. Catheter ablation of electrical storm due to
monomorphic ventricular tachycardia in patients with nonischemic cardiomyopathy: acute
results and its effect on long-term survival. Pacing and clinical electrophysiology : PACE.
Dec 2010;33(12):1504-1509. PMID 20636312
13. GeneDx® Personal Communication. 4/29/2010 2010.
14. Correlagan® Personal Communication. 4/27/2010 2010.
15. PGxHealth® Personal Communication. 4/22/2010 2010.
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16. Das KJ, Ingles J, Bagnall RD, et al. Determining pathogenicity of genetic variants in
hypertrophic cardiomyopathy: importance of periodic reassessment. Genet Med. Oct 10
2013. PMID 24113344
17. Andreasen C, Nielsen JB, Refsgaard L, et al. New population-based exome data are
questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur
J Hum Genet. Sep 2013;21(9):918-928. PMID 23299917
18. Zou Y, Wang J, Liu X, et al. Multiple gene mutations, not the type of mutation, are the
modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. Mol Biol
Rep. Jun 2013;40(6):3969-3976. PMID 23283745
19. Center BBATE. Genetic testing for predisposition to inherited hypertrophic cardiomyopathy.
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20. Harvard CardioGenomics website. 2010; http://cardiogenomics.med.harvard.edu/home.
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CARDIOMYOPATHY
POLICY NUMBER
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GENETIC TESTING FOR PREDISPOSITION TO INHERITED HYPERTROPHIC
CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
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21787999
X. POLICY HISTORY
MP-2.248
TOP
CAC 6/26/2012 New policy. Adopted BCBSA. Genetic testing for predisposition to
inherited hypertrophic cardiomyopathy is considered medically necessary for specified
criteria. FEP variation added.
CAC 9/24/13 Consensus review. References updated but no changes to the policy
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CARDIOMYOPATHY
POLICY NUMBER
MP-2.248
statements. Rationale added.
CAC 7/22/14 Consensus review. References and rationale updated but no
changes to the policy statements
CAC 7/21/15 Consensus review. No change to policy statements. References and
rationale updated. No coding changes.
CAC 7/26/16 Consensus review. Clarification made to the not medical necessary
policy statement to indicate that familial testing should be in a family member
with established HCM. Otherwise, policy statements unchanged. Background,
references and rationale updated. Policy Guidelines added. Appendix added.
Coding reviewed.
Administrative Update 11/23/16 -Variation section reformatted.
Administrative Update 1/1/17: Added new code 81439; effective 1/1/17.
Top
Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance
Company®, Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the
BlueCross BlueShield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs
and provider relations for all companies.
APPENDIX
Appendix Table 1. Categories of Genetic Testing Addressed in MP-2.248
Category
1. Testing of an affected individual’s germline to benefit the individual
1a. Diagnostic
1b. Prognostic
1c. Therapeutic
2. Testing cancer cells from an affected individual to benefit the individual
2a. Diagnostic
2b. Prognostic
2c. Therapeutic
3. Testing an asymptomatic individual to determine future risk of disease
4. Testing of an affected individual’s germline to benefit family members
5. Reproductive testing
5a. Carrier testing: preconception
5b. Carrier testing: prenatal
5c. In utero testing: aneuploidy
5d. In utero testing: mutations
5e. In utero testing: other
5f. Preimplantation testing with in vitro fertilization
Addressed
X
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