Medical Policy: 02.04.37 

Original Effective Date: October 2012 

Reviewed: June 2018 

Revised: June 2018 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

There are currently genetic tests available for multiple cardiac conditions. This includes various channelopathies and other systemic conditions effecting cardiac health.  With the multitude of genetic tests commercially available, there is great importance in choosing the most appropriate test. Confining your analysis to a smaller number of genes (ie, targeted panels over more broad approaches such as clinical exome/genome sequencing) will reduce the number of uncertain and incidental variants.

 

Currently, interpretation of cardiac ion channelopathy variation testing is complicated by several factors. The pathophysiologic significance of each of the discrete variations is an important part of the interpretation of genetic analysis. Laboratories that test for cardiac ion channelopathies keep a database of known pathologic mutations; however, these are mainly proprietary and may vary among different laboratories. In addition, the probability that a specific variation is pathophysiologically significant is greatly increased if the same variation has been reported in other cases. However, a variation may also be found that has not definitely been associated with a disorder and therefore may or may not be pathologic.

 

As the prevalence of genetic testing has increased, the limitations become more important to the practicing physician. Testing may reveal a change in the patient’s genome from the typical sequence, but certifying a variation as the clinical cause of a patient’s disease remains a challenge.

 

Coronary Artery Disease

The expression levels of various genes in circulating white blood cell or whole blood samples have been reported to discriminate between cases of obstructive coronary artery disease (CAD) and healthy controls. Multiplex gene expression testing can be combined with other risk factors to predict the likelihood of obstructive CAD in patients who present with chest pain or other suggestive symptoms, or in asymptomatic patients who are at high risk of CAD.

 

Heart disease is the leading cause of mortality in the U.S. and, together with cerebrovascular disease, accounted for 31% of deaths in 2007. Individuals with signs and symptoms of obstructive coronary artery disease (CAD), the result of a chronic inflammatory process that ultimately results in progressive luminal narrowing and acute coronary syndromes, may be evaluated with a variety of tests according to prior risk. Coronary angiography is the gold standard for diagnosing obstructive CAD, but it is invasive and associated with a low but finite risk of harm. Thus, coronary angiography is recommended for patients at a high prior risk of CAD according to history, physical findings, electrocardiogram, and biomarkers of cardiac injury. For patients initially assessed at low-to-intermediate risk, observation and noninvasive diagnostic methods, which may include imaging methods such as coronary computed tomographic angiography, may be recommended. Nevertheless, even noninvasive imaging methods have potential risks of exposure to radiation and contrast material. In addition, coronary angiography has a relatively low yield despite risk stratification recommendations. In one study of nearly 400,000 patients without known CAD undergoing elective coronary angiography, approximately 38% were positive for obstructive CAD (using the CAD definition, stenosis of 50% or more of the diameter of the left main coronary artery or stenosis of 70% or more of the diameter of a major epicardial or branch vessel that was more than 2.0 mm in diameter; result was 41% if using the broader definition, stenosis of 50% or more in any coronary vessel). Thus, methods of improving patient risk prediction prior to diagnostic testing are needed.

 

A CAD classifier has been developed based on the expression levels, in whole blood samples, of 23 genes plus patient age and sex. This information is combined in an algorithm to produce a score from 1 to 40, with higher values associated with a higher likelihood of obstructive CAD. The test is marketed as Corus CAD™ (CardioDx, Inc.). The intended population is stable, nondiabetic patients suspected of CAD either because of symptoms, a high-risk history, or a recent positive or inconclusive test result by conventional methods.

 

The Corus CAD™ test is not a manufactured test kit and has not been reviewed by the U.S. Food and Drug Administration (FDA). Rather, it is a laboratory-developed test (LDT), offered by the Clinical Laboratory Improvement Act (CLIA)-licensed CardioDx Commercial Laboratory.

 

Brugada Syndrome

Brugada Syndrome  is characterized by cardiac conduction abnormalities which increase the risk of syncope, ventricular arrhythmia, and sudden cardiac death. Inheritance occurs in an autosomal dominant manner with patients typically having an affected parent. Children of affected parents have a 50% chance of inheriting the variation. The instance of de novo variations is very low and is estimated to be only 1% of cases.

 

The disorder primarily manifests during adulthood although ages between two days and 85 years have been reported. Geno typical males are more likely to be affected than geno typical females (approximately an 8:1 ratio). Brugada syndrome is estimated to be responsible for 12% of SCD cases For both genders there is an equally high risk of ventricular arrhythmias or sudden death. Penetrance is highly variable, with phenotypes ranging from asymptomatic expression to death within the first year of life. Management has focused on the use of implantable cardiac defibrillators (ICD) in patients with syncope or cardiac arrest and isoproterenol for electrical storms. Patients who are asymptomatic can be closely followed to determine if ICD implantation is necessary.

 

The diagnosis of Brugada Syndrome is considered definite when the characteristic EKG pattern is present with at least one of the following clinical features: documented ventricular arrhythmia, sudden cardiac death in a family member <45 years old, characteristic EKG pattern in a family member, inducible ventricular arrhythmias on EP studies, syncope, or nocturnal agonal respirations.

 

Long QT Syndrome

Congenital long QT syndrome (LQTS) is an inherited disorder characterized by the lengthening of the repolarization phase of the ventricular action potential, increasing the risk of arrhythmic events, such as torsades de pointes, which may in turn result in syncope and sudden cardiac death. Management has focused on the use of beta blockers as first-line treatment, with pacemakers or implantation cardioverter defibrillators (ICD) as second-line therapy.

Currently, there are three major LQTS genes (KCNQ1, KCNH2, and SCN5A) that account for approximately 75% of the disorder. The 10 minor LQTS-susceptibility genes collectively account for less than 5% of LQTS cases.

 

Major LQTS Genes

  • KCNQ1 (LQT1)
  • KCNH2 (LQT2)
  • SCN5A (LQT3)

 

Minor LQTS Genes

  • AKAP9
  • CACNA1C
  • CALM1
  • CALM2
  • CAV3
  • KCNE1
  • KCNE2
  • KCNJ5
  • SCN4B
  • SNTA1

 

Congenital LQTS usually manifests itself before the age of 40 years. Frequently, syncope or sudden death occurs during physical exertion or emotional excitement. LQTS may be considered when a long QT interval is incidentally observed on an ECG. Diagnostic criteria for LQTS have been established, which focus on ECG findings and clinical and family history (i.e., Schwartz criteria, see following table). The Schwartz criteria are commonly used as a diagnostic scoring system for LQTS. The most recent version of this scoring system is shown below. A score of 4 or greater indicates a high probability that LQTS is present; a score of 2 to 3, a moderate-to-high probability; and a score of 1 or less indicates a low probability of the disorder. Prior to the availability of genetic testing, it was not possible to test the sensitivity and specificity of this scoring system; and since there is still no perfect gold standard for diagnosing LQTS.

 

LQTS is a disorder that may lead to catastrophic outcomes, ie, sudden cardiac death in otherwise healthy individuals. Diagnosis using clinical methods alone may lead to underdiagnosis of LQTS, thus exposing undiagnosed patients to the risk of sudden cardiac arrest. For patients in whom the clinical diagnosis of LQTS is uncertain, genetic testing may be the only way to further clarify whether LQTS is present. Patients who are identified as genetic carriers of LQTS variations have a non-negligible risk of adverse cardiac events even in the absence of clinical signs and symptoms of the disorder. Therefore, treatment is likely indicated for patients found to have a LQTS variation, with or without other signs or symptoms.

 

There is not sufficient evidence to conclude that the information obtained from genetic testing on risk assessment leads to important changes in clinical management. Most patients will be treated with betablocker therapy and lifestyle modifications, and it has not been possible to identify a group with low enough risk to forego this conservative treatment. Conversely, for high-risk patients, there is no evidence suggesting that genetic testing influences the decision to insert an ICD and/or otherwise intensify treatment.

 

Diagnostic Scoring System for LQTS
Critera Points
Electrocardiographic findings
QTc
>480 msec 3
460-470 msec 2
<450 msec 1
History of torsades de pointes 2
T-wave alternans 1
Notched T-waves in three leads 1
Low heart rate for age 0.5
Clinical history
Syncope brought on by stress 2
Syncope without stress 1
Congenital deafness 0.5
Family history
Family members with definite LQTS 1
Unexplained sudden death in immediate family members younger than 30 years of age 0.5
  • High Probability ≥ 4 points
  • Moderate Probability 2-3 points
  • Low Probability <2 points

 

Short QT Syndrome

Short QT syndrome is a condition that can cause a disruption of the heart's normal rhythm (arrhythmia). In people with this condition, the heart (cardiac) muscle takes less time than usual to recharge between beats. The term "short QT" refers to a specific pattern of heart activity that is detected with an electrocardiogram (EKG), which is a test used to measure the electrical activity of the heart. In people with this condition, the part of the heartbeat known as the QT interval is abnormally short.

 

SQTS has been linked predominantly to variations in 3 genes KCNH2, KCNJ2, and KCNQ1. Some individuals with SQTS do not have a variation in these genes suggesting changes in other genes may also cause this disorder.

 

No studies were identified that provide evidence for the clinical utility of genetic testing for SQTS. Clinical sensitivity for the test is low with laboratory testing providers estimating a yield as low as 15%.

 

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Mutations in 4 genes are known to cause CPVT, and investigators believe other unidentified loci are involved as well. Currently, only 55% to 65% of patients with CPVT have an identified causative mutation. Mutations to the gene encoding the cardiac ryanodine receptor (RYR2) or to KCNJ2 result in an autosomal dominant form of CPVT. CASQ2 (cardiac calsequestrin) andTRDN-related CPVT exhibit autosomal recessive inheritance. Some authors have reported heterozygotes for CASQ2 and TRDN mutations for rare, benign arrhythmias. RYR2 mutations represent the majority of CPVT cases (50-55%), with CASQ2 accounting for 1% to 2% and TRDN accounting for an unknown proportion of cases.

 

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition characterized by an abnormal heart rhythm (arrhythmia). As the heart rate increases in response to physical activity or emotional stress, it can trigger heartbeat called ventricular tachycardia.

 

Management of CPVT is primarily with beta-blockers. If protection is incomplete (ie, recurrence of syncope or arrhythmia), then flecainide may be added. If recurrence continues, an ICD may be necessary with optimized pharmacologic management continued postimplantation.  Lifestyle modification with the avoidance of strenuous exercise is recommended for all CPVT patients.

 

Familial thoracic aortic aneurysm and dissection (familial TAAD)

Familial TAAD is believed to account for at least 20 percent of thoracic aortic aneurysms and dissections. In the remainder of cases, the abnormalities are thought to be caused by factors that are not inherited, such as damage to the walls of the aorta from aging, tobacco use, injury, or disease.

 

Ambry Genetics offers “TAADNEXT,” an NGS panel which simultaneously analyzes 20 genes that are associated with TAADs, MFS and related disorders. Published studies on the analytic validity of genetic testing for connective tissue disorders associated with thoracic aortic aneurysms are lacking. The sensitivity of sequence analysis for individual variations for these disorders is generally high for certain disorders, but lower, for others. Conventional testing for these disorders has historically consisted of sequencing for individual variations associated with one suspected disorder, followed by duplication/deletion analysis if sequencing is negative. More recently, panel testing by next-generation sequencing (NGS) tests has been developed to test for multiple syndromes simultaneously.

 

Dilated Cardiomyopathy

DCM is defined as the presence of left ventricular enlargement and dilatation in conjunction with significant systolic dysfunction. Dilated cardiomyopathy has an estimated prevalence of 1 in 2700 in the United States. The age of onset for DCM is variable, ranging from infancy to the eighth decade, with most individuals developing symptoms in the fourth through sixth decade. Primary clinical manifestations of DCM are heart failure and arrhythmias. Symptoms of heart failure, such as dyspnea on exertion and peripheral edema, are the most common presentation of DCM. These symptoms are generally gradual in onset and slowly progressive over time. Progressive myocardial dysfunction also may lead to electrical instability and arrhythmias. Symptoms of arrhythmias may include light-headedness, syncope or sudden cardiac arrest.

 

Many genetic variations on more than 40 different genes have been associated with DCM. This remains an active area of research, and it is likely that many more variations will be identified in the future. Analytic validity of genetic testing for DCM is expected to be high when testing is performed by direct sequencing or next-generation sequencing. In contrast, clinical validity is not high. The percentage of patients with idiopathic DCM who have a genetic variation (clinical sensitivity) is relatively low.

 

Treatment of DCM is similar to that for other causes of heart failure. This includes medications to reduce fluid overload and relieve strain on the heart, and lifestyle modifications such as salt restriction. Patients with clinically significant arrhythmias also may be treated with antiarrhythmic medications, pacemaker implantation, and/or an automatic implantable cardiac defibrillator (AICD). AICD placement for primary prevention also may be performed if criteria for low ejection fraction and/or other clinical symptoms are present. End-stage DCM can be treated with cardiac transplantation.

 

Hypertrophic Cardiomyopathy

Familial hypertrophic cardiomyopathy (HCM) is an inherited condition that is caused by a variation in 1 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 variations is currently available through a number of commercial laboratories.

 

For individuals at risk for HCM (first-degree relatives), genetic testing is most useful when there is a known variation in the family. In this situation, genetic testing will establish the presence or absence of the same variation in a close relative with a high degree of certainty. Absence of this variation 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. Therefore, genetic testing may be considered medically necessary for first-degree relatives of individuals with a known pathologic variation.

 

For at-risk individuals without a known variation 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. For at-risk individuals who have a family member with HCM who tests negative for pathologic variations, genetic testing is not medically necessary.

 

The primary benefit of identifying genetic abnormality is to ensure family members determine if they also have hypertrophic cardiomyopathy, or the gene responsible for it. If the individual has a gene identified, but the family member does not, that family member will not move to be further screened for hypertrophic cardiomyopathy in the future and no special surveillance would be necessary.

 

Arrhythmogenic Cardiomyopathy (ACM)/Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)/ Arrhythmogenic Right Ventricular Dysplasia (ARVD)

ARVC/ARVD is a rare type of cardiomyopathy that occurs if the muscle tissue in the right ventricle dies and is replaced by fat or scar tissue:

  • This process disrupts the heart's electrical system, causing arrhythmias.  
  • It usually affects teens and young adults.  
  • Symptoms include heart palpitations and fainting after physical activity. 
  • It can cause sudden cardiac arrest in young athletes.
  • It may require implantation of a device to prevent death from an arrhythmia

 

Non-Compacted Left Ventricular Cardiomyopathy

Variations in several genes have been found to cause left ventricular noncompaction. Mutations in the MYH7 and MYBPC3 genes have been estimated to cause up to 30 percent of cases; mutations in other genes are each responsible for a small percentage of cases. However, the cause of the condition is often unknown.

 

It is unclear how genetic mutations cause left ventricular noncompaction. During normal development before birth, cardiac muscle gets condensed (compacted), becoming smooth and firm. Mutations in certain genes likely lead to changes in this process, resulting in a left ventricular cardiac muscle that is not compacted but is thick and spongy, leading to left ventricular noncompaction.

 

Panel Testing

In cases where the family member’s genetic diagnosis is unavailable, testing is available through either single-gene testing or panel testing. Panels for cardiac ion channelopathies are diagnostic test panels that may fall into one of several categories: panels that include variants for a single condition; panels that include variants for multiple conditions (indicated plus non-indicated conditions); and panels that include variants for multiple conditions (clinical syndrome for which clinical diagnosis not possible).

 

With the addition of multiple gene panels available for cardiology, the number of panel tests, and number of gene variations examined have continued to expand. The use of panel testing in cardiology includes, but not limited, to the following examples of panel testing:

  • Invitae Arrhythmia Comprehensive Panel
  • Invitae Arrthymia and Cardiomyopathy Comprehensive Panel
  • Invitae Brugada Syndrom Panel
  • Cardiomyopathy Panel (Knight Diagnostic Laboratories)
  • Arrhythmia Panel (Blueprint Genetics) 
  • Comprehensive Cardiology Panel (Blueprint Genetics) 
  • Brugada Syndrome Panel (Blueprint Genetics) 
  • Comprehensive Cardiovascular Deletion/Duplication Panel (EGL Genetic Diagnostics) 
  • Brugada Syndrome Panel (Centogene) 
  • Comprehensive Arrythmia Panel (GeneDx)
  • Cardiomyopathy and Arrhythmia Panel (ARUP Labratories) 
  • Brugada Syndrome NGS Panel (Fulgent Genetics) 
  • GeneSeq (Labcorp) 
  • The FAMILION test (Transgenomics)
  • CardioNext (Ambry Genetics) 
  • Rhythm NeXT/Rhythm First (Ambry Genetics) 
  • Cardio Familial Arrhythmia or Cardiomyopathy Panels (GenSeq)
  • TAADNext (Ambry Genetics) 
  • Pan Cardiovascular Panel (Baylor) 
  • Pan Cardiomyopathy/Pan Arrhythmia (Baylor)

 

Examples of Cardiac Genetic Panel Testing (not all inclusive)

The FAMILION test is currently performed exclusively at designated laboratory facilities provided by Transgenomics® Inc. (New Haven, CT) The FAMILION family of tests detects genetic variations that can cause cardiac channelopathies, cardiomyopathies, and other cardiopathies.  Cardiac channelopathies are rare, potentially lethal inherited heart conditions, including Long QT Syndrome (LQTS), Short QT Syndrome (SQTS), Brugada Syndrome (BrS) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT).  Cardiomyopathies are potentially lethal progressive diseases that affect the heart muscle including, Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Conduction Disease associated with DCM (CD-DCM), and Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Other cardiopathies include Marfan Syndrome and familial Thoracic Aortic Aneurysms and Aortic Dissections (Marfan/TAAD).  According to information available online the test “may use some reagents produced for research purposes only."

 

HCM First, CM Next, DCM Next, RhythmNext, RhythmFirst, CPVTNext, ARVDNext, CardioNext are all multi-gene test panels performed by AmbryGeneticsa (Aliso Viejo, CA).

 

CardioNext is a next generation sequencing (NGS) and deletion/duplication panel of 84 genes associated with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular dysplasia (ARVD), left ventricular non-compaction (LVNC), restrictive cardiomyopathy, long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome. This panel also includes genes that cause cardiomyopathy that is associated with inherited muscular dystrophies, as well as some genes associated with congenital heart defects.

 

RhythmNext is a panel including 34 genes associated with arrhythmogenic right ventricular dysplasia (ARVD), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), short QT syndrome (SQTS), other arrhythmias/channelopathies, as well as sudden cardiac arrest.

 

Guidelines

The Heart Rhythm Societ (HRS) and the European Heart Rhythm Associan (EHRA)

The Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) jointly published an expert consensus statement on genetic testing for channelopathies and cardiomyopathies. This document made the following specific recommendations concerning testing for LQTS, CPVT, Brugada Syndrom, and SQTS.

 

LQTS Class I
  • Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing is recommended for any patient in whom a cardiologist has established a strong clinical index of suspicion for LQTS based on examination of the patient’s clinical history, family history, and expressed electrocardiographic (resting 12-lead ECGs and/or provocative stress testing with exercise or catecholamine infusion) phenotype.
  • Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing is recommended for any asymptomatic patient with QT prolongation in the absence of other clinical conditions that might prolong the QT interval (such as electrolyte abnormalities, hypertrophy, bundle branch block, etc., ie, otherwise idiopathic) on serial 12-lead ECGs defined as QTc .480 ms (prepuberty) or .500 ms (adults).
  • Mutation-specific genetic testing is recommended for family members and other appropriate relatives subsequently following the identification of the LQTS-causative mutation in an index case.

 

LQTS Class II
  • Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing may be considered for any asymptomatic patient with otherwise idiopathic QTc values .460 ms (prepuberty) or .480 ms (adults) on serial 12-lead ECGs.
     

 

CPVT Class I
  • Comprehensive or CPVT1 and CVPT2 (RYR2 and CASQ2) targeted CPVT genetic testing is recommended for any patient in whom a cardiologist has established a clinical index of suspicion for CPVT based on examination of the patient’s clinical history, family history, and expressed electrocardiographic phenotype during provocative stress testing with cycle, treadmill, or catecholamine infusion. Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the CPVT-causative mutation in an index case.

 

BrS Class I
  • Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the BrS-causative mutation in an index case.

 

BrS Class IIa
  • Comprehensive or BrS1 (SCN5A) targeted BrS genetic testing can be useful for any patient in whom a cardiologist has established a clinical index of suspicion for BrS based on examination of the patient’s clinical history, family history, and expressed electrocardiographic (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype.

 

BrS Class III
  • Genetic testing is not indicated in the setting of an isolated type 2 or type 3 Brugada ECG pattern

 

SQTS Class I
  • Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the SQTS-causative mutation in an index case.

 

SQTS Class IIb
  • Comprehensive or SQT1-3 (KCNH2, KCNQ1, and KCNJ2) targeted SQTS genetic testing may be considered for any patient in whom a cardiologist has established a strong clinical index of suspicion for SQTS based on examination of the patient’s clinical history, family history, and electrocardiographic phenotype.

 

*Class I: “is recommended” when an index case has a sound clinical suspicion for the presence of a channelopathy with a high PPV for the genetic test (>40%) with a signal to noise ratio of >10 AND/OR the test may provide diagnostic or prognostic information or may change therapeutic choices.; Class IIa: “can be useful”; Class IIb: “may be considered”; Class III (“is not recommended”): The test fails to provide any additional benefit or could be harmful in the diagnostic process.

 

The Evaluation of Genomic Applications in Practice and Prevention Working Group

(EWG) found insufficient evidence to recommend testing for the 9p21 genetic variant or 57 other variants in 28 genes to assess risk for cardiovascular disease (CVD) in the general population, specifically heart disease and stroke. The EWG found that the magnitude of net health benefit from use of any of these tests alone or in combination is negligible. The EWG discourages clinical use unless further evidence supports improved clinical outcomes. Based on the available evidence, the overall certainty of net health benefit is deemed “Low.”

 

The Canadian Cardiovascular Society and Canadian Hearth Rhythm Society

They published a joint position paper in 2011.24 Genetic testing was recommended for cardiac arrest survivors with LQTS for the purpose of familial screening as well as those with syncope with QTc prolongation as well as asymptomatic patients with QTc prolongation with a high clinical suspicion of LQTS. For clinically suspect CPVT, testing is recommended for the purpose of familial screening.

 

Heart Failure Society (HFS)/European Heart Rhythm Association (EHRA) (2008)

Regarding ARVC:

  • Comprehensive or targeted (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) ACM/ARVC genetic testing can be useful for patients satisfying task force diagnostic criteria for ACM/ARVC. (Class IIa)
  • Genetic testing may be considered for patients with possible ACM/ARVC (1 major or 2 minor criteria) according to the 2010 task force criteria. (Class IIb)
  • Genetic testing is not recommended for patients with only a single minor criterion according to the 2010 task force criteria. (Class III)
  • Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the ACM/ARVC-causative mutation in an index case. (Class I)

 

European Society of Cardiology and European Association for Cardio-Thoracic Surgery

The society published guidelines for the management of atrial fibrillation (AF). Regarding genetic testing, the guideline notes while genomic analysis may provide an opportunity to improve the diagnosis and management of AF in the future, routine genetic testing for common gene variants associated with AF cannot be recommended at present. The guideline also notes that monogenic defects only account for 3–5% of all patients with AF, even in younger populations. Furthermore, there is no clear link between detected mutations and specific outcomes or therapeutic needs. Genetic testing is not recommended in the general population.

 

Prior Approval:

Not applicable

 

Policy:

Multi-gene next generation panels are not medically necessary. This includes panels that test variants for multiple conditions (indicated plus non-indicated conditions); and panels that include variants for multiple non-specific conditions (clinical syndrome for which clinical diagnosis is not possible). The medical necessity of testing is based on medical factors for individual conditions and not panels that test for multiple syndromes or cardiac conditions without clinical cause. Testing for the individual condition will be expected when medically necessary criteria is present.  The following is a list of common multi-condition panels (not all inclusive):

  • Arrhythmia Panels or Channelopathies Panels (multiple labs)
  • CardioNext (Ambry Genetics)
  • GeneSeq: Cardio Familial Cardiomyopathy Profile (Labcorp)
  • HCMNext (Ambry Genetics)
  • Invitae Arrhythmia & Cardiomyopathy Comprehensive Panel (invitae)
  • Pan Cardiomyopathy Panel
  • RhythmNext/Rhythm First (Ambry Genetics)
  • Familion (Transgenomics)
  • Cardiomyopathy Panel (Knight Diagnostic Laboratories)
  • Arrhythmia Panel (Blueprint Genetics) 
  • Comprehensive Cardiology Panel (Blueprint Genetics) 
  • Comprehensive Cardiovascular Deletion/Duplication Panel (EGL Genetic Diagnostics) 
  • Comprehensive Arrythmia Panel (GeneDx)
  • Cardiomyopathy and Arrhythmia Panel (ARUP Labratories) 
  • Cardio Familial Arrhythmia or Cardiomyopathy Panels (GenSeq)

 

Panel testing is considered not medically necessary with any known condition/genetic variation and/or when focused genetic testing for a specific condition is possible.

 

Short OT Syndrome (genes KCNH2, KCNQ1, KCNJ2)

Genetic testing for Short QT Syndrome is considered medically necessary for the following indications:

  • Variation-specific genetic testing is recommended for first or second degree family members following the identification of the SQTS-causative variation in an index case, or
  • Comprehensive or SQT1-3 (KCNH2, KCNQ1, KCNJ2) targeted SQTS genetic testing may be considered for any patient in whom a cardiologist has established a strong clinical index of suspicion for SQTS based on examination of the patient’s clinical history, family history, and electrocardiographic phenotype but a diagnosis is not certain.

 

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) (genes RYR2 and CASQ2)

Genetic testing in patients with suspected CPTV may be considered medically necessary for the following indications:

  • To confirm the diagnosis of CPVT in individuals who demonstrate exercise-induced ventricular arrhythmias in the presence of an unremarkable resting electrocardiogram (ECG) and absence of structural cardiac abnormalities
  • Variation-specific genetic testing is recommended for first-degree blood relatives following the identification of the CPVT-causative variation in an index case.

 

Brugada Syndrome (BrS) (gene SCN5A)

Testing for Brugada Syndrome may be considered medically necessary for the following indications:

 

  • For first or second degree family members following the identification of the BrS-causative variation in an index case or
  • Comprehensive or BrS1 (SCN5A) targeted BrS genetic testing can be useful for any patient in whom a cardiologist has established a clinical index of suspicion for BrS based on examination of the patient’s clinical history, family history, and expressed electrocardiographic (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype.

 

Genetic testing is not indicated and therefore not medically necessary in the setting of an isolated type 2 or type 3 Brugada ECG pattern 

 

Long QT Syndrome (LQTS) (genes KCNQ1, KCNH2, and SCN5A)

Genetic testing in patients with suspected congenital long QT syndrome may be considered medically necessary for the following indications:

Individuals who do not meet the clinical criteria for LQTS (ie, those with a Schwartz score <4), but who have:

  • a first- or second-degree relative with a known LQTS variation; or
  • a first- or second-degreerelative diagnosed with LQTS by clinical means whose genetic status is unavailable

 

Genetic testing for LQTS to determine prognosis and/or direct therapy in patients with known LQTS is considered medically necessary only when needed to determine index case variation.

 

Genetic testing for predisposition to LQTS is considered not medically necessary for patients with a family history of LQTS in which an index case has tested negative for mutations.

 

Hypertrophic Cardiomyopathy (HCM) (genes MYH7, MYBPC3, TNNT2, and TNNI3)

Genetic testing for predisposition to hypertrophic cardiomyopathy (HCM) may be considered medically necessary for individuals who are at risk for development of HCM:

  • Individual has a first-degree relative with established HCM, when there is a known pathogenic gene variation present in that affected relative AND
  • The individual to be tested has been clinically screened (for example, with EKG, echocardiogram, or cardiac magnetic resonance imaging [MRI]) and does not have a diagnosis of HCM.
  • OR when testing is needed to determine the index case variation.

 

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 variations.

 

Genetic testing for determining the diagnosis and for management of all other hereditary cardiomyopathies, including but not limited to, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), dilated, restrictive, and left ventricular noncompaction cardiomyopathies, is considered not medically necessary for all indications.

 

Dilated Cardiomyopathy (DCM) (genes ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CRYAB,CSRP3, DES, DMD, DSG2, EYA4, GATAS1, LAMA4, LDB3, LMNA, MYBPC3, MYH6, MYH7, MYPN, PLN, PSEN1, PSEN2, RBM20, SCN5A, SGDC, TAZ, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, VCL) 

Genetic testing for dilated cardiomyopathy is considered not medically necessary.

 

Clinical utility of genetic testing for DCM is uncertain. For a patient who is diagnosed with idiopathic DCM, the presence of a genetic variation will not change treatment or prognosis. For an individual at risk due to genetic DCM in the family, genetic testing can identify whether the variation has been inherited. However, it is uncertain how knowledge of a variation will improve outcomes for an asymptomatic individual. Early treatment based on a genetic diagnosis is unproven. Uncertain accuracy of predictive testing makes it uncertain whether changes in management will improve outcomes.

 

Thoracic Aortic Aneurysms and Dissections (TAAD) (genes ACTA2, TGFBR2, FBN1)

Genetic testing for thoracic aortic aneurysms and dissections (TAAD) medically necessary for:

  • First degree relatives of persons with genetically confirmed TAAD.
  • Genetic testing for thoracic aortic aneurysms and dissections (TAAD) is considered not medically necessary for any other indication, including but not limited to patients diagnosed with TAAD or when needed to determine index case variation.

 

Marfan Syndrome (genes FBN1, MYH11, ACTA2, TGFBR1/2)

Genetic testing of gene FBN1for Marfan Syndrome is considered medically necessary for

  • First degree relatives of persons with genetically confirmed Marfan. 
  • In patients with clinically suspected, but no concrete diagnosis of Marfan Synrome

 

Genetic testing of genes MYH11, ACTA2, TGFBR1/2 is considered medically necessary for:

  • First degree relatives of persons with genetically confirmed Marfan. AND
  • In patients with clinically suspected, but no concrete diagnosis of Marfan Synrome AND
  • Testing of gene FBN1 has been completed and is negative

 

Testing for Marfan syndrome is considered not medically necessary in all other clinical scenarios.

 

Expanded panel testing for Marfan syndrome is considered not medically necessary.

 

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)/ Arrhythmogenic Right Ventricular Dysplasia (ARVD)

Genetic testing (including but not limited to the following genes (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) may be considered medically necessary to confirm a clinical diagnosis in those with clinical suspicion of ARVC/ARVD.

 

Genetic testing (including but not limited to the following genes (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) may be considered medically necessary for first degree relatives of persons with genetically confirmed ARVC/ARVD.

 

Miscellaneous

Gene expression testing to predict coronary artery disease is considered investigational.

 

Genetic testing for atrial fibrillation is considered not medically necessary.

 

Genetic testing to find variants that correlate to cardiac structural genetics, including but not limited to aortic root size, is not proven at this time and is considered not medically necessary.

 

Genetic testing (including but not limited to the following genes: MYH7 and MYBPC3) is condidered not medically necessary for the diagnosis of left ventricular noncompaction.

 

Genetic testing panels for syndromes associated with thoracic aortic aneurysms and dissections, and related disorders that are not limited to focused genetic testing are considered not medically necessary.

 

Clinical utility of gene expression assays/panels has not been demonstrated. There hasn't been convincing evidence that the use of gene expression scores reduce unnecessary clinical evaluations. There is insufficient evidence in the clinical literature demonstrating that these test have a role in clinical decision-making or have a beneficial effect on health outcomes. Further studies are needed to determine the analytic validity, clinical validity and clinical utility of these tests. Testing for multiple conditions without clinical indications for testing has not been proven to change net health outcomes.

 

Specific Genes tested for cardiac conditions may include but are not limited to:

Under code 81403:
  • KCNJ2 (potassium inwardly-rectifying channel, subfamily J, member 2) (eg, Andersen-Tawil syndrome), full gene sequence

 

Under code 81405:
  • CASQ2 (calsequestrin 2 [cardiac muscle]) (eg, catecholaminergic polymorphic ventricular tachycardia), full gene sequence

 

Under code 81406:
  • KCNH2(potassium voltage-gated channel, subfamily H [ead-related], member 2) (eg, short QT syndrome, long QT syndrome), full gene sequence
  • KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) (eg, short QT syndrome, long QT syndrome), full gene sequence

 

Under code 81407:
  • SCN5A (sodium channel, voltage-gated, type V, alpha subunit) (eg, familial dilated cardiomyopathy), full gene sequence

 

Under code 81408:
  • RYR2 (ryanodine receptor 2 [cardiac]) (eg, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular dysplasia), full gene sequence or targeted sequence analysis of > 50 exons
  • FBN1 (fibrillin 1) (eg, Marfan syndrome), full gene sequence

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • 81599  Unlisted multianalyte assay with algorithmic analysis
  • 84999  Unlisted chemistry procedure
  • S3861 Genetic testing, sodium channel, voltage-gated, type V, alpha subunit (SCN5A) and variants for suspected Brugada Syndrome
  • 81403 Molecular pathology procedure, Level 3 (eg, >10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants of 1 exon, loss of heterozygosity [LOH], uniparental disomy [UPD])
  • 81404 Molecular pathology procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis)
  • 81405 Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis,tation scanning or duplication/deletion variants of 11-25 exons, regionally targeted cytogenomic array analysis)
  • 81406 Molecular pathology procedure, Level 7 (eg, analysis of 11-25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia)
  • 81407 Molecular pathology procedure, Level 8 (eg, analysis of 26-50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform)
  • 81408 Molecular pathology procedure, Level 9 (eg, analysis of >50 exons in a single gene by DNA sequence analysis)
  • 81413 Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); genomic sequence analysis panel, must include sequencing of at least 10 genes, including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A
  • 81414 Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); duplication/deletion gene analysis panel, must include analysis of at least 2 genes, including KCNH2 and KCNQ1
  • 81439 Hereditary cardiomyopathy (eg, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), genomic sequence analysis panel, must include sequencing of at least 5 cardiomyopathy-related genes (eg, DSG2, MYBPC3, MYH7, PKP2, TTN)
  • 81493 Coronary artery disease, mRNA, gene expression profiling by real-time RT-PCR of 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score
  • 81410 Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); genomic sequence analysis panel, must include sequencing of at least 9 genes, including FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK
  • 81411 Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1
  • 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

 

Selected References:

  • Rosenberg S, Elashoff MR, Lieu HD, Brown BO, Kraus WE, Schwartz RS, Voros S, Ellis SG, Waksman R, McPherson JA, Lansky AJ, Topol EJ; PREDICT Investigators. Whole blood gene expression testing for coronary artery disease in nondiabetic patients: major adverse cardiovascular events and interventions in the PREDICT trial. J Cardiovasc Transl Res. 2012 Jun;5(3):366-74. Epub 2012 Mar 7. PubMed PMID: 22396313; PubMed Central PMCID: PMC3349850.
  • Versteylen MO, Joosen IA, Shaw LJ, Narula J, Hofstra L. Comparison of Framingham, PROCAM, SCORE, and Diamond Forrester to predict coronary atherosclerosis and cardiovascular events. J Nucl Cardiol. 2011 Oct;18(5):904-11. Epub 2011 Jul 19. PubMed PMID: 21769703; PubMed Central PMCID: PMC3175044.
  • Mahler SA, Hiestand BC, Goff DC Jr, Hoekstra JW, Miller CD. Can the HEART score safely reduce stress testing and cardiac imaging in patients at low risk for major adverse cardiac events? Crit Pathw Cardiol. 2011 Sep;10(3):128-33. PubMed PMID: 21989033; PubMed Central PMCID: PMC3289967.
  • Colombo G, Gertow K, Marenzi G, Brambilla M, De Metrio M, Tremoli E, Camera M. Gene expression profiling reveals multiple differences in platelets from patients with stable angina or non-ST elevation acute coronary syndrome. Thromb Res. 2011 Aug;128(2):161-8. Epub 2011 Mar 21. PubMed PMID: 21420725.
  • Grayson BL, Wang L, Aune TM. Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes. Genes Immun. 2011 Jul;12(5):341-51. doi: 10.1038/gene.2011.13. Epub 2011 Mar 3. PubMed PMID: 21368773; PubMed Central PMCID: PMC3137736.
  • Elashoff MR, Wingrove JA, Beineke P, Daniels SE, Tingley WG, Rosenberg S, Voros S, Kraus WE, Ginsburg GS, Schwartz RS, Ellis SG, Tahirkheli N, Waksman R, McPherson J, Lansky AJ, Topol EJ. Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. 2011 Mar 28;4:26. PubMed PMID: 21443790; PubMed Central PMCID: PMC3072303
  • Ashley EA, Hershberger RE, Caleshu C, Ellinor PT, Garcia JG, Herrington DM, Ho CY, Johnson JA, Kittner SJ, Macrae CA, Mudd-Martin G, Rader DJ, Roden DM, Scholes D, Sellke FW, Towbin JA, Van Eyk J, Worrall BB; American Heart Association Advocacy Coordinating Committee. Genetics and cardiovascular disease: a policy statement from the American Heart Association. Circulation. 2012 Jul 3;126(1):142-57. Epub 2012 May 29. PubMed PMID: 22645291.
  • ECRI Institute. Genetic testing and cardiovascular disease: Where are we now? Health Technology Trends.; Plymouth Meeting (PA). 09/01/2012.
  • ECRI Institute. Corus CAD (CardioDx, Inc.) for Genomic Testing of Obstructive Coronary Artery Disease. ECRI Hotline Response. Plymouth Meeting (PA). 09/25/2012.
  • Ackerman MJ, Marcou CA, Tester DJ. Personalized medicine: genetic diagnosis for inherited cardiomyopathies/channelopathies. Rev Esp Cardiol 2013; 66(4):298-307.
  • Bennett MT, Sanatani S, Chakrabarti S et al. Assessment of genetic causes of cardiac arrest. Can J Cardiol 2013; 29(1):100-10.
  • Ackerman MJ, Priori SG, Willems S et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the Eur Soc Cardiol 2011;13(8):1077-109.
  • Hersheberger RE M, A. Dilated Cardiomyopathy Overview GeneReviews 2013;
  • Hershberger RE, Morales A, Siegfried JD. Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals. Genet Med. Nov 2010;12(11):655-667. PMID 20864896
  • McNally E, MacLeod H, Dellefave-Castillo L. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. 2005 Apr 18 [Updated 2014 Jan 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.
  • Schwartz PJ, Ackerman MJ, George AL Jr, Wilde AA. Impact of genetics on the clinical management of channelopathies. J Am Coll Cardiol. 2013 Jul 16;62(3):169-80.
  • Roston TM, Vinocur JM, Maginot KR, et al. Catecholaminergic Polymorphic Ventricular Tachycardia in Children: An Analysis of Therapeutic Strategies and Outcomes from an International Multicenter Registry. Circ Arrhythm Electrophysiol. 2015 Feb 24.
  • Giudici V, Spanaki A, Hendry J, et al. Sudden arrhythmic death syndrome: diagnostic yield of comprehensive clinical evaluation of pediatric first-degree relatives. Pacing Clin Electrophysiol. 2014 Dec;37(12):1681-5.
  • Lopes L, Syrris P, et. al. Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy Heart. 2015;101:294-30.
  • Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: executive summary: a Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;124:2761–96.
  • Ladapo JA, Lyons H, Yau M, et al. Enhanced Assessment of Chest Pain and Related Symptoms in the Primary Care Setting Through the Use of a Novel Personalized Medicine Genomic Test: Results From a Prospective Registry Study. Am J Med Qual. May 5 2014. PMID 24798176
  • Semsarian C, Ingles J, Maron MS, Maron BJ . New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65:1249–1254. doi: 10.1016/j.jacc.2015.01.019.
  • Tawil R and Venance S. Andersen-Tawil syndrome. Gene Reviews. University of Washington, Seattle. Updated 2015 Sep 3
    Semsarian C, Ingles J, Maron MS, Maron BJ . New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65:1249–1254. doi: 10.1016/j.jacc.2015.01.019.
  • Alders M, Cristiaans I. Long QT syndrome. Gene Reviews. Updated 2015 Jun 18. Funded by the NIH. Developed at the University of Washington, Seattle. Accessed Oct 6, 2016.
  • Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Accessed Oct. 6, 2016.
  • Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO). Eur J Cardiothorac Surg. 2016 Sep 23.
  • McNally E, MacLeod H, DelleFave –Castillo L. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Gene Reviews. Updated 2017 May 25.
  • National Library of Medicine (US). Genetics Home Reference [Internet]. Bethesda (MD): The Library; 2017 Sep 26 [cited 2017 Oct 2].
  • Yamagata K, Horie M, Aiba T, et al.(2017) Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. Circulation. Jun 6 2017;135(23):2255-2270.
  • Mellor G, Laksman ZWM, Tadros R, et al.(2017) Mellor G, Laksman ZWM, Tadros R, et al. Genetic Testing in the Evaluation of Unexplained Cardiac Arrest: From the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry). Circ Cardiovasc Genet. Jun 2017;10(3)
  • Tester DJ, Ackerman MJ. GENETICS OF LONG QT SYNDROME. Methodist DeBakey Cardiovascular Journal. 2014;10(1):29-33.

 

Policy History:

  • June 2018 - Annual review, Policy revised
  • June 2017 - Annual review, Policy revised
  • June 2016 - Annual review, Policy revised
  • June 2015 - Annual review, Policy revised
  • July 2014 - Annual review, Policy revised
  • September 2013 - Annual review, Policy renewed
  • October 2012 - New policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.