HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.☆
Introduction
This international consensus statement is the collaborative effort of three medical societies representing electrophysiology in North America, Europe and Asian-Pacific area: the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA) and the Asia Pacific Heart Rhythm Society. The objective of the consensus document is to provide clinical guidance for diagnosis, risk stratification and management of patients affected by inherited primary arrhythmia syndromes. 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 clinical data on patients affected by channelopathies.
This document does not address the indications of genetic testing in patients affected by inherited arrhythmias and their family members. Diagnostic, prognostic, and therapeutic implications of the results of genetic testing also are not included in this document because this topic has been covered by a recent publication1 coauthored by some of the contributors of this consensus document, and it remains the reference text on this topic. Guidance for the evaluation of patients with idiopathic ventricular fibrillation, sudden arrhythmic death syndrome and sudden unexplained death in infancy, which includes genetic testing, are provided as these topics were not covered in the previous consensus statement.
Developing guidance for genetic diseases requires adaptation of the methodology adopted to prepare guidelines for clinical practice. Documents produced by other medical societies have acknowledged the need to define the criteria used to rank the strength of recommendation for genetic diseases.2
The most obvious difference encountered for inherited diseases is that randomized and/or blinded studies do not exist in this field. Therefore most of the available data derive from registries that have followed patients and recorded outcome information. As a consequence, all consensus recommendations are level of evidence (LOE) C (i.e., based on experts’ opinions).
The consensus recommendations in this document use the commonly used Class I, IIa, IIb and III classification and the corresponding language: “is recommended” for Class I consensus recommendation; “can be useful” for a Class IIa consensus recommendation; “may be considered” to signify a Class IIb consensus recommendation; and “should not” or “is not recommended” for a Class III consensus recommendation (failure to provide any additional benefit and may be harmful).
In the consensus document, the following terms will be defined as:
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Syncope: In the context of inherited arrhythmogenic disorders, the occurrence of “syncope” is an important indicator of arrhythmic risk. Although there is no definition to differentiate a syncopal episode caused by ventricular arrhythmias from an otherwise unexplained syncope, in the context of this document, the term “syncope” implies the exclusion of events that are likely due to vasovagal events such as those occurring during abrupt postural changes, exposure to heat and dehydration, emotional reactions to events such as blood drawing, etc. We refer to the guidelines of ESC and AHA/ACCF for the differential diagnoses of syncope.3, 4 Symptomatic individuals: The term “symptomatic” refers to individuals who have experienced ventricular arrhythmias (usually ventricular tachycardia or resuscitated ventricular fibrillation), or syncopal episodes (see definition above). The presence of symptoms is, in some of the channelopathies, an independent predictor of cardiac arrest at follow-up.
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Arrhythmic events: The term refers to the occurrence of symptomatic or asymptomatic sustained or nonsustained spontaneous ventricular tachycardia, or unexplained syncope/resuscitated cardiac arrest.
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Concealed mutation-positive patients: This term is used to refer to individuals without clinical symptoms or phenotype of a channelopathy who carry the genetic defect present in clinically affected members of the family.
When considering the guidance from this document, it is important to remember that there are no absolutes governing many clinical situations. The final judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all relevant circumstances. Recommendations are based on consensus of the writing group following the Heart Rhythm Society’s established consensus process. It is recognized that consensus does not mean unanimous agreement among all writing group members. We identified the aspects of patients' care for which a true consensus could be found. Surveys of the entire writing group were used. The authors received an agreement that was equal to or greater than 84% on all recommendations; most recommendations received agreement of 94% or higher.
This statement is directed to all health care professionals who are involved in the management of (1) individuals who survived a cardiac arrest at a young age (usually defined as <40 years) in the absence of a clinical diagnosis of cardiac disease, despite extensive clinical assessment; (2) family members of individuals who died suddenly at young age with a negative autopsy; (3) in patients and family members in whom the diagnosis of a channelopathy is clinically possible, likely, or established; and (4) young patients with unexplained syncope.
All members of this document writing group provided disclosure statements of all relationships that might present real or perceived conflicts of interest. Disclosures for all members of the writing group are published in Appendix A.
Section snippets
Long QT Syndrome (LQTS)
LQTS is diagnosed: In the presence of an LQTS risk score ≥3.5 in the absence of a secondary cause for QT prolongation and/or In the presence of an unequivocally pathogenic mutation in one of the LQTS genes or In the presence of a QT interval corrected for heart rate using Bazett's formula (QTc) ≥500 ms in repeated 12-lead electrocardiogram (ECG) and in the absence of a secondary cause for QT prolongation. LQTS can be diagnosed in the presence of aExpert Consensus Recommendations on LQTS Diagnosis
Brugada Syndrome (BrS)
BrS is diagnosed in patients with ST-segment elevation with type 1 morphology ≥2 mm in ≥1 lead among the right precordial leads V1, V2, positioned in the 2nd, 3rd or 4th intercostal space occurring either spontaneously or after provocative drug test with intravenous administration of Class I antiarrhythmic drugs. BrS is diagnosed in patients with type 2 or type 3 ST-segment elevation in ≥1 lead among the right precordial leads V1, V2Expert Consensus Recommendations on Brugada Syndrome Diagnosis
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
CPVT is diagnosed in the presence of a structurally normal heart, normal ECG, and unexplained exercise or catecholamine-induced bidirectional VT or polymorphic ventricular premature beats or VT in an individual <40 years of age. CPVT is diagnosed in patients (index case or family member) who have a pathogenic mutation. CPVT is diagnosed in family members of a CPVT index case with a normal heart who manifest exercise-induced PVCs orExpert Consensus Recommendations on CPVT Diagnosis
Sjome (SQTS)
SQTS is diagnosed in the presence of a QTc ≤330 ms. SQTS can be diagnosed in the presence of a QTc <360 ms and one or more of the following: a pathogenic mutation, family history of SQTS, family history of sudden death at age ≤40, survival of a VT/VF episode in the absence of heart disease.Expert Consensus Recommendations on Short QT Syndrome Diagnosis
ICD implantation is recommended in symptomatic patients with Expert Consensus Recommendations on Short QT Syndrome Therapeutic Interventions Class I
Early Repolarization (ER)
ER syndrome is diagnosed in the presence of J-point elevation ≥1 mm in ≥2 contiguous inferior and/or lateral leads of a standard 12-lead ECG in a patient resuscitated from otherwise unexplained VF/polymorphic VT ER syndrome can be diagnosed in an SCD victim with a negative autopsy and medical chart review with a previous ECG demonstrating J-point elevation ≥1 mm in ≥2 contiguous inferior and/or lateral leads of a standard 12-leadExpert Consensus Recommendations on Early Repolarization Diagnosis
Progressive Cardiac Conduction Disease (PCCD)
Progressive cardiac conduction disease (PCCD) is diagnosed in the presence of unexplained progressive conduction abnormalities in young (<50 years) individuals with structurally normal hearts in the absence of skeletal myopathies, especially if there is a family history of PCCD.Expert Consensus Recommendations on Progressive Cardiac Conduction Disease Diagnosis
Pacemaker implantation isExpert Consensus Recommendations on Progressive Cardiac Conduction Disease Therapeutic Interventions Class I
Unexplained Cardiac Arrest: Idiopathic VF
IVF is defined as a resuscitated cardiac arrest victim, preferably with documentation of VF, in whom known cardiac, respiratory, metabolic and toxicological etiologies have been excluded through clinical evaluation.Expert Consensus Recommendations on Idiopathic Ventricular Fibrillation Diagnosis
Genetic testing in IVF can be useful when there is a suspicion of a specific genetic disease following clinicalExpert Consensus Recommendations on Idiopathic Ventricular Fibrillation Evaluation Class IIa
Unexplained Sudden Cardiac Death: Sudden Unexplained Death Syndrome (SUDS) and Sudden Unexplained Death in Infancy (SUDI)
It is recommended that an unexplained sudden death occurring in an individual older than 1 year of age is known as “sudden unexplained death syndrome” (SUDS). It is recommended that a SUDS death with negative pathological and toxicological assessment is termed “sudden arrhythmic death syndrome” (SADS). It is recommended thatExpert Consensus Recommendations on Sudden Unexplained Death Syndrome Diagnosis Expert Consensus Recommendations on Sudden Unexplained Death Syndrome Evaluation Class I
Inherited Arrhythmia Clinics
Inherited Arrhythmia Clinic Expert Consensus Recommendation Class I Patients (probands) and first-degree relatives with a diagnosed or suspected inherited cardiovascular disease as a potential cause of SCD (SUDS/SUDI) should be evaluated in a dedicated clinic with appropriately trained staff.
The evaluation and treatment of families suspected of having inherited arrhythmias requires a multidisciplinary team and approach. The presentation often is that of a proband or family member who has
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Developed in partnership with the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology, and the Asia Pacific Heart Rhythm Society (APHRS); and in collaboration with the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the Pediatric and Congenital Electrophysiology Society (PACES) and the Association for European Pediatric and Congenital Cardiology (AEPC).
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Representative for Association for European Pediatric and Congenital Cardiology
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Representative for Pediatric and Congenital Electrophysiology Society
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Representative for American Heart Association
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Representative for American College of Cardiology