News from the Heart Rhythm SocietyHRS/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)
Section snippets
Preamble
This international consensus statement provides the state of genetic testing for the channelopathies and cardiomyopathies. It summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of genetic testing for these potentially heritable cardiac conditions. This document focuses primarily on the state of genetic testing for the 13 distinct entities detailed and the relative diagnostic,
Table of Contents
Introduction and Summary of Expert Consensus Recommendations (see Table 1)
Table 1. Expert Consensus Recommendations
Table 2. Summary of Common Cardiac Channelopathy/Cardiomyopathy-Associated Genes (>5% of Disease)
Table 3. Yield and Signal-to-Noise Associated with Disease-Specific Genetic Testing
- I
State of Genetic Testing for Long QT Syndrome (LQTS)
- a
Expert Consensus Recommendations
- b
Diagnostic Implications of LQTS Genetic Testing
- i
Summary of the Common LQTS Genes (see Table 2)
- ii
Index Cases
- iii
Family Screening
- i
- c
- a
Expert Consensus Recommendations
- 1
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.
- 2
Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing is
Expert Consensus Recommendations
- 1
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.
- 2
Mutation-specific genetic testing is recommended for family members and appropriate relatives following the
Expert Consensus Recommendations
- 1
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.
- 2
Genetic testing is not indicated in the setting of an isolated type 2 or type 3 Brugada ECG pattern.
- 3
Mutation-specific genetic testing is recommended
Expert Consensus Recommendations
- 1
Genetic testing may be considered as part of the diagnostic evaluation for patients with either isolated CCD or CCD with concomitant congenital heart disease, especially when there is documentation of a positive family history of CCD.
- 2
Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the CCD-causative mutation in an index case.
This section pertains to familial forms of conduction disease, not to (common) non-familial
Expert Consensus Recommendations
- 1
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.
- 2
Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the SQTS-causative mutation in an index case.
The short QT syndrome
Expert Consensus Recommendations
- 1
Genetic testing is not indicated for atrial fibrillation at this time.
- 2
SNP genotyping in general and SNP rs2200733 genotyping at the 4q25 locus for AF is not indicated at this time based on the limited outcome data currently available.
Atrial fibrillation (AF) is the most common sustained arrhythmia and its prevalence is increasing. AF is associated with an increased risk of stroke, heart failure, dementia, and death.143 Symptoms of AF include palpitations, fatigue, dyspnea on exertion, and chest
Expert Consensus Recommendations
- 1
Comprehensive or targeted (MYBPC3, MYH7, TNNI3, TNNT2, TPM1) 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.
- 2
Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the HCM-causative mutation in an index case.
Hypertrophic
Expert Consensus Recommendations
- 1
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.
- 2
Genetic testing may be considered for patients with possible ACM/ARVC (1 major or 2 minor criteria) according to the 2010 task force criteria.
- 3
Genetic testing is not recommended for patients with only a single minor criterion according to the 2010 task force criteria.
- 4
Mutation-specific genetic testing is recommended for
Expert Consensus Recommendations
- 1
Comprehensive or targeted (LMNA and SCN5A) DCM genetic testing is recommended for patients with DCM and significant cardiac conduction disease (i.e., first, second, or third-degree heart block) and/or a family history of premature unexpected sudden death.
- 2
Genetic testing can be useful for patients with familial DCM to confirm the diagnosis, to recognize those who are at highest risk of arrhythmia and syndromic features, to facilitate cascade screening within the family, and to help with family
Expert Consensus Recommendations
- 1
LVNC genetic testing can be useful for patients in whom a cardiologist has established a clinical diagnosis of LVNC based on examination of the patient's clinical history, family history, and electrocardiographic/echocardiographic phenotype.
- 2
Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of an LVNC-causative mutation in the index case.
Left ventricular noncompaction (LVNC) is a recently classified form of inherited
Expert Consensus Recommendations
- 1
RCM genetic testing may be considered for patients in whom a cardiologist has established a clinical index of suspicion for RCM based on examination of the patient's clinical history, family history, and electrocardiographic/echocardiographic phenotype.
- 2
Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of an RCM-causative mutation in the index case.
Restrictive cardiomyopathy (RCM) is rare. Little has been reported on its
Expert Consensus Recommendations
- 1
In the survivor of an Unexplained Out-of-Hospital Cardiac Arrest, genetic testing should be guided by the results of medical evaluation and is used for the primary purpose of screening at-risk family members for subclinical disease.
- 2
Routine genetic testing, in the absence of a clinical index of suspicion for a specific cardiomyopathy or channelopathy, is not indicated for the survivor of an Unexplained Out-of-Hospital Cardiac Arrest.
Out-of-hospital cardiac arrest (OHCA) occurs most commonly in
Expert Consensus Recommendations
- 1
For all SUDS and SIDS cases, collection of a tissue sample is recommended (5–10 mL whole blood in EDTA tube, blood spot card, or a frozen sample of heart, liver, or spleen) for subsequent DNA analysis/genetic testing.
- 2
In the setting of autopsy-negative SUDS, comprehensive or targeted (RYR2, KCNQ1, KCNH2, and SCN5A) ion channel genetic testing may be considered in an attempt to establish probable cause and manner of death and to facilitate the identification of potentially at-risk relatives and
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The Heart Rhythm Society and European Heart Rhythm Association endorsed the document in April of 2011. The American Heart Association endorsed the document in June of 2011.
Correspondence and reprint requests: Sonja Olson, Heart Rhythm Society, 1400 K Street NW, Washington, DC 20005. E-mail address: [email protected].