HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies


This Expert Consensus Statement is a summary of recommendations from the Heart Rhythm Society (HRS) and European Heart Rhythm Association (EHRA) on genetic testing for patients with cardiomyopathies and channelopathies. Ten points to remember are:

1. Genetic counseling is recommended for all patients and relatives with suspected heritable cardiomyopathies and channelopathies. However, the yield of genetic testing is highly variable, and treatment decisions should not rely solely on a genetic test result.

2. Genetic test results are probabilistic, not deterministic. Some ‘positive tests’ may represent ‘Variants of Uncertain Significance’ (VUS), and may represent a false-positive test. Likewise, false-negative tests in diseases for which mutations have not been identified are not uncommon.

3. A positive genetic test often does not offer therapeutic guidance or patient prognosis, and variability in disease phenotype and penetrance must be taken into account.

4. Genetic testing is recommended for patients and family members with a clinical suspicion of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, dilated cardiomyopathy with significant cardiac conduction disease (first- to third-degree heart block), and sudden infant death syndrome.

5. Genetic testing may be useful for patients with suspected Brugada syndrome (but not isolated type 2 or 3 pattern without signs/symptoms), short QT syndrome, arrhythmogenic cardiomyopathy meeting task force diagnostic criteria, dilated cardiomyopathy with a familial pattern (regardless of electrocardiogram findings), left ventricular noncompaction, and restrictive cardiomyopathy. The yield of testing in these circumstances tends to be less than the above conditions.

6. Genetic testing is not indicated at this time for atrial fibrillation, patient meeting one minor criterion for arrhythmogenic cardiomyopathy, or adult survivors of unexplained cardiac arrest without a suspected specific channelopathy/cardiomyopathy.

7. When a causative mutation is identified in an index case, genetic testing and counseling of family members is usually recommended. The role is much less clear when a VUS is identified.

8. For hypertrophic cardiomyopathy, knowledge of an underlying gene mutation has a limited role in risk assessment and management of a patient. Management and patient monitoring still rely on clinical factors.

9. It is estimated that 25-35% of sudden unexplained deaths (SUDs) from ages 1-35 years and up to 15% of sudden infant deaths (SIDs) may be due to known channelopathy-associated genes. Reimbursement for testing is an obstacle.

10. Given the complexity of genetic testing and testing interpretation, and the implications for patients and families, referral to a center that offers comprehensive cardiogenetic evaluation, patient/family counseling, and understands reimbursement and financial implications of testing is warranted.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure

Keywords: Infant Mortality, Electrocardiography, Genetic Testing, Heart Arrest, Penetrance, Mutation, Atrioventricular Block, Genetic Therapy, Cardiomyopathies, Channelopathies, Risk Assessment, Genetic Counseling, Pregnancy, Brugada Syndrome, False Positive Reactions, Sudden Infant Death, Long QT Syndrome, Heart Rate, Tachycardia, Consensus, Prognosis, Tachycardia, Ventricular, Phenotype, Heart Failure

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