Genetic Testing for HCM: The case for insurance reimbursement in the USA

This section was written by Lisa Salberg of the HCMA. We understand this is an evolving area and data is likely to change rapidly. Case and in point within day of the this section being completed Blue Cross and Blue Shield Association in partnership with Kaiser Permanente (see attachment to the right) issued their own document which came to very similar conclusions to the HCMA’s position. The purpose of this section is to make publicly available the HCMA’s position on the appropriateness of the payment of clinical genetic testing services for families with hypertrophic cardiomyopathy. This document is not intended to address individual cases but can be used to submit an appeal to an insurance company if they deny coverage for these service.

Hypertrophic Cardiomyopathy Association’s Position Paper:  Genetic Testing in HCM – 2010

The role of clinical genetic testing for HCM is growing and questions about its necessity, usefulness, methods of reimbursement from health insurance companies and questions over terminology are increasing.  The purpose of this document is to provide practical insight and rationale for the various useful applications of genetic testing in HCM.

Often the diagnosis of HCM is made based on the results of cardiac imaging, commonly echocardiography or MRI.  This phenotype, clinical presentation of hypertrophy or thickening, only begins to tell the story of why this heart happens to be abnormal in appearance. As our knowledge of HCM has grown we now understand that not all hypertrophy/thickening is created by the same genetic cause.  Specifically, we know that some phenotypes have a very different genetic mutation and, in fact, are treated very differently from other forms of cardiac hypertrophy.

In January 2009 The Journal of Cardiac Failure published a guidelines document entitled “Genetic Evaluation of Cardiomyopathy–A Heart Failure Society of America Practice Guideline1“.

“Substantial progress has been made recently in understanding the genetic basis of cardiomyopathy.  Cardiomyopathies with known genetic causes include hypertrophic cardiomyopathy (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC/D) and left ventricular noncompaction (LVNC).  HCM, DCM, and RCM have been recognized as distinct clinical entities for decades whereas ARVC/D. and LVNC are relative newcomers to the field.  Hence the clinical and genetic knowledge for each cardiomyopathy varies, as do recommendations and strength of evidence.”

The guidelines discuss the role of genetic testing for these conditions based upon 4 categories:

1) That the testing “is recommended” as part of routine care an exception should be minimized; 2) “should be considered” indicates that a majority of patients should receive the intervention with some discretion in application to individual patients; 3) “may be considered” indicates individualization of therapy is indicated and 4) “is not recommended” indicates the therapeutic interventions should not be used.

Coding was assigned based on “Levels” of medical evidence for genetic evaluation and cardiomyopathy screenings based upon diagnosis with three levels being identified in the document.  The question to be answered with this data is “Does the test correlate with the outcome of interest?”

  • Level A- this indicates when the specific genetic test or clinical test has a high correlation with the cardiomyopathic disease of interest in a reasonably large study from multiple centers.
  • Level B- indicates specific genetic tests or clinical test has a high correlation with the cardiomyopathic disease of interest in small or single center study.
  • Level C- indicates genetic test or clinical correlation with the cardiomyopathic disease of interest in case reports.

A second scoring for evaluating the clinical utility strength of evidence criteria answers the question “Does performing this test result in improved patient outcomes?”

  • Level A- Randomized controlled clinical trials.  May be assigned on the basis of a single randomized trial.
  • Level B- Cohort and case control studies.  Post-hoc, subgroup analysis, and meta-analysis.  Prospective observational studies or registries.
  • Level C- Expert opinion.  Observational studies-epidemiologic findings.  Safety reporting from large-scale use in practice.

Based upon the criteria set forth in the guidelines document the role of genetic testing/ genetic screening in HCM is as follows:

  • After a careful family history for three generations for all patients with hypertrophic cardiomyopathy genetic testing “is recommended”.  Level A
  • Clinical screening (genetic testing) for hypertrophic cardiomyopathy families with asymptomatic first-degree relatives “is recommended”.  Level A.
  • Genetic testing “should be considered” for the one clearly affected person (index case) in the family to facilitate family screening and management in cases of hypertrophic cardiomyopathy. Level A

In Table 4 of the guidelines titled: Cardiomyopathies Associated with Systemic Disease hypertrophic cardiomyopathy was listed with over 20 specific diseases where a clinical manifestation within the heart can look like hypertrophic cardiomyopathy.  The majority of these conditions have very different treatments than sarcomere mutation hypertrophic cardiomyopathy.  Identifying the specific genetic mutation responsible for the hypertrophy in the heart can dictate significant deviations in management strategy.  Many times the first clinical indication of disease is left ventricular hypertrophy (LVH) which becomes defined as HCM; however the underlying cause may originate from a very different genetic cause.

There are several of these phenocopies or mimickers that have vastly different management strategies which could benefit the patient with prompt diagnosis, treatment and family screening possibilities.  They include the following:

  • Pompe syndrome requires immediate treatment and enzyme replacement therapy.
  • Danon disease requires dietary changes and, in a high number of cases, listing for cardiac transplantation at a very early age.
  • Fabry disease requires enzyme replacement therapy in addition to clinical evaluation of other organs.
  • Several other syndromes that can appear to be HCM would benefit from early identification and proper assessment including Noonan, Costello, Barth and LEAPARD syndrome.

Within the guideline document there is specific discussion regarding HCM in childhood and the identification that benign LVH, specifically in an infant, can look identical to disease is deadly as in Pompe’s disease.  At the HCMA we have seen a number of these cases ourselves.  We have seen several cases in young males with a diagnosis originally of simple LVH, which turned to a diagnosis hypertrophic cardiomyopathy.  However,  only after genetic analysis they were found positive for Danon’s disease.    Several interesting examples of this have been seen at the HCMA, with patientswho were thought to have HCM, only to find it was Danon’s disease and promptly rapid placement on a heart transplant list.

In adult cases we have had a number of HCM diagnoses with the appropriate diagnosis of Fabry’s disease after genetic analysis.  The numbers of clarification of diagnosis are expanding daily and those who had been misdiagnosed are now on more appropriate treatment paths.

Serial screenings and hypertrophic cardiomyopathy:

For over 20 years the management strategy for families living with hypertrophic cardiomyopathy has been described in the literature and followed routinely by cardiologists over the world.  Serial screening in hypertrophic cardiomyopathy family includes an echocardiogram, electrocardiogram and evaluation by a cardiologist every year2 (an annual cost per child of between $1500 and $4000 based on location) between the ages of 12 and 20 and every five years throughout the remainder of life (an annual cost per child of between $1500 and $4000 based on geographic location).  Not only is this a time consuming and expensive process for families and the medical community it is significantly stressful and anxiety producing for the families.   The cost to screen an adolescent from 12 to 20 would be an estimated $20,000 and an additional $30,000 into adulthood to age 65 (without consideration of inflation) totaling $50,000 over the life of one individual.  The average HCMA family has 10 potentially affected relatives, a cost of $500,000 for traditional clinical screening over their lives.  Due to the nature of HCM, as an autosomal dominant disorder, there is a 50/50 chance the off spring of an affected individual will inherite the gene.  The location of a genetic mutation in the index patient has the potential to save an average of $250,000 per family.

The advent of clinically available genetic testing has the ability to minimize cost, stress and demands on infrastructure by identifying only those at true genetic risk for developing HCM and eliminating those who do not harbor the genetic mutation from further genetic screening.  While the cost associated with genetic testing on an index patient may seem high ($3,000-$5,700) it is not; and, in many cases, represents the cost of only ONE annual individual family screening.  The cost of testing potentially affected family members with genetic testing is minimal in comparison to annual clinical evaluations over life costing between $300 and $900 on average.   The total cost for genetic testing on an average HCMA family would be $5,000 and would identify those who are in need of further evaluation and those who are free of having additional screening conducted.

In 2010 with “Health Care Reform”, also known as Affordable Care Act 3, as reality, we must all look for ways to minimize costs and taxing the health care system when other options are available.  The use of genetic testing has proven it can reduce the number of family members who require serial screening annually and throughout adulthood.   We have countless cases in which mutations discovered in parents, aunts, uncles and grandparents were used to screen dozens of relatives (as young as infants) to confirm who requires additional surveillance and who does not.   Health insurance companies can save millions of dollars in clinical evaluations, testing and imaging by reimbursing reasonable fees for clinical genetic testing to identify those who truly require testing at this time.

Yield of genetic testing:

While we would like to say that we have identified all of the genetic mutations responsible for HCM, we have not.  It is believed we have identified approximately 70% of them.  However the yield of an individual case, based on the experience of the HCMA, will vary based on several factors including, ordering physician/Center, the clinical presentation and the family history.

Due to the complex heterogenic presentation of HCM, testing is best ordered by a physician with a specific clinical interest in the condition.  Such physicians can be found at HCM Centers of Excellence or HCM Programs around the USA.  In such programs the yield from genetic testing can reach 65-70%.  If a patient has been evaluated by one of these programs and the test is simply being ordered by a home town cardiologist, the yield remains high; however, if a patient has not been evaluated by a Center of Excellence or HCM Program then the yield may be as low as 30%.  In the event of an infant with possible Pompe disease there is often no time to seek a national expert for clinical evaluation, nor do we believe this important testing should be delayed.

In cases where there is a questionable diagnosis of HCM and such issues as “athlete’s heart” or benign LVH needs to be ruled out, it should be understood that the absence of a genetic marker previously identified for HCM does not exclude the possibility of this clinical finding being true “HCM”.  Further, the finding of a mutation does confirm that it is true HCM.  This fact can become very confusing for some people and genetic counseling can prove highly effective in helping them understand the implications of testing.

Understanding Results:

While many physicians are skilled at interpreting clinical test results, genetic tests rarely have results that fall into the terms many are familiar with such as, positive or negative, high or low. These terms are not used in genetic testing and one of the many reasons the HCMA suggests testing with an HCM program and consultation with a genetic counselor.   Currently in the area of genetic testing of an index patient, the first in a family to be tested, it is a question of are we able to identify a mutation that has been previously found to cause HCM.  While each company has its own coding system and terms for the meaning of each mutation result generally fall into 4 categories.

  • Confirmed disease causing – this mutation has been seen in others, or a mutation in a similar location and type, and has been reported in the medical literature.
  • Likely disease causing – while no other mutation has been reported it is similar to those that have been reported and it believed to be the cause of HCM.
  • Not likely to cause disease – while the genetic mutation looks similar to those which cause HCM, a large number of people in a similar ethnic make up carry the mutation yet show no disease, thus it is felt to be a benign mutation.
  • No mutation found – no known mutation has been identified–this is not a “negative” result, simply a “nothing found”.  As we have yet to identify all mutations, up to 30% of those testing will receive this result.  These people may wish to participate in research programs seeking to identify the genetic cause of their HCM.

Seeking a result in an index patient can be likened to drawing a complex and intricate map, for example, of the entire United States, while looking for a specific location similar to an address –of the state, town, street, house and room within that house where the mutation is located.  When seeking family genetic testing you already know the location, the address, thus you are conducting a much simpler, and cheaper test.

In the event of “Confirmed disease causing” mutation has been found, information should be shared with all relatives. They should be informed and offered the opportunity for testing. Using the thought of looking up, over and down the family tree is advised – parents of the index patient, then siblings, should a parent be a gene carrier.   Over to the siblings of the index patient and then down again to their children should they be gene carriers. This should be continued down to children of the index patient and down to their children, if they are gene carriers.

In the event of a “likely disease causing” mutation was found, additional testing may be helpful to determine its meaning in a family, including screening the parents of the index patient, if available, to see if either carries the mutation and what their heart looks like.   Clinical consideration by an expert in HCM should be sought in conducting genetic testing of family members with this form of an identified mutation as its meaning is not completely understood within the family.

In a large number of cases multiple mutations can be indentified and the meaning of each mutation should be closely evaluated.  Two or more “Confirmed disease causing” mutations have been reported to present as more severe disease, in which case, clinical evaluation will be needed by an HCM expert.

Terminology (for purposes of this document):

Index patient: A person whom has been identified with clinically diagnosed HCM and in whom genetic testing is being conducted.

Mutation: A variation in a person’s genetic code that can cause HCM at any point in life.

Genetic Testing/Clinical Genetic Testing: a blood test or saliva test preformed in a CLIA approved laboratory.

For more information about genetic testing in HCM please visit or call the HCMA directly at 973-983-7429.


1.     R. Hershberger et al. Genetic evaluation of cardiomyopathy a Heart Failure Society of America practice guideline J Cardiac Fail 2009;15:83-97

2.     Maron BJ  et al. Task Force on Clinical Expert Consensus Documents. American College of Cardiology; Committee for Practice Guidelines. European Society of Cardiology. J Am Coll Cardiol. 2003 Nov 5;42(9):1687-713

3.      H.R.3590 Patient Protection and Affordable Care Act,  H.R.3200 – America’s Affordable Health Choices Act of 2009, AMENDMENT IN THE NATURE OF A SUBSTITUTE TO H.R. 4872