HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes

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).

[1]  A. Leenhardt,et al.  Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia , 2009, Circulation.

[2]  P. Bjerregaard.  Proposed diagnostic criteria for short QT syndrome are badly founded. , 2011, Journal of the American College of Cardiology.

[3]  Michael J Ackerman,et al.  The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis. , 2009, Journal of the American College of Cardiology.

[4]  J. Ruijter,et al.  Exercise-Induced ECG Changes in Brugada Syndrome , 2009, Circulation. Arrhythmia and electrophysiology.

[5]  C. Mcgorrian,et al.  Sudden cardiac death in 14- to 35-year olds in Ireland from 2005 to 2007: a retrospective registry. , 2011, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[6]  D. Tester,et al.  Protein Kinase A–Dependent Biophysical Phenotype for V227F-KCNJ2 Mutation in Catecholaminergic Polymorphic Ventricular Tachycardia , 2009, Circulation. Arrhythmia and electrophysiology.

[7]  A. Wilde,et al.  Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in The Netherlands. , 2010, Heart rhythm.

[8]  M. Ackerman,et al.  Videoscopic Left Cardiac Sympathetic Denervation for Patients With Recurrent Ventricular Fibrillation/Malignant Ventricular Arrhythmia Syndromes Besides Congenital Long-QT Syndrome , 2012, Circulation. Arrhythmia and electrophysiology.

[9]  Michael J Ackerman,et al.  Mutation and gender-specific risk in type 2 long QT syndrome: implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome. , 2011, Heart rhythm.

[10]  R. Frank,et al.  Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome. , 2007, European heart journal.

[11]  E. Green,et al.  A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome , 1995, Cell.

[12]  J. Brugada,et al.  Brugada syndrome: report of the second consensus conference. , 2005, Heart rhythm.

[13]  S. Viskin,et al.  Risk of sudden death among young individuals with J waves and early repolarization: putting the evidence into perspective. , 2011, Heart rhythm.

[14]  H. Huikuri,et al.  Prevalence and Prognostic Significance of Short QT Interval in a Middle-Aged Finnish Population , 2007, Circulation.

[15]  D. Corrado,et al.  Sudden cardiac death in young people with apparently normal heart. , 2001, Cardiovascular research.

[16]  S. Priori,et al.  Role of Genetic Analyses in Cardiology: Part I: Mendelian Diseases: Cardiac Channelopathies , 2006, Circulation.

[17]  Peter J. Schwartz,et al.  Diagnostic Criteria for the Long QT Syndrome An Update , 1993, Circulation.

[18]  J. Healey,et al.  Clinical ResearchHeart Rhythm DisorderPrevalence and Characteristics of Early Repolarization in the CASPER Registry: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry , 2011 .

[19]  Michael J. Ackerman,et al.  Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. , 2011, Journal of the American College of Cardiology.

[20]  J. Osborn.  Experimental hypothermia; respiratory and blood pH changes in relation to cardiac function. , 1953, The American journal of physiology.

[21]  A. Wilde,et al.  Familial Evaluation in Catecholaminergic Polymorphic Ventricular Tachycardia: Disease Penetrance and Expression in Cardiac Ryanodine Receptor Mutation–Carrying Relatives , 2012, Circulation. Arrhythmia and electrophysiology.

[22]  Hirotaka Oda,et al.  High prevalence of early repolarization in short QT syndrome. , 2010, Heart rhythm.

[23]  D. Kastner,et al.  Autosomal Recessive Catecholamine- or Exercise-Induced Polymorphic Ventricular Tachycardia: Clinical Features and Assignment of the Disease Gene to Chromosome 1p13-21 , 2001, Circulation.

[24]  G. Bonsel,et al.  Genetic knowledge and counselling skills of Dutch cardiologists: sufficient for the genomics era? , 2003, European heart journal.

[25]  G. Bonsel,et al.  Obtaining insurance after DNA diagnostics: a survey among hypertrophic cardiomyopathy mutation carriers , 2010, European Journal of Human Genetics.

[26]  M. Iannettoni,et al.  Delayed maximal response to left cardiac sympathectomy for catecholaminergic polymorphic ventricular tachycardia. , 2010, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[27]  J. Cryan,et al.  Sudden unexplained death in childhood (1–4 years) in Ireland: an epidemiological profile and comparison with SIDS , 2012, Archives of Disease in Childhood.

[28]  E. Schulze-Bahr,et al.  Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. , 2009, Journal of Clinical Investigation.

[29]  Derick R. Peterson,et al.  Risk Factors for Aborted Cardiac Arrest and Sudden Cardiac Death in Children With the Congenital Long-QT Syndrome , 2008, Circulation.

[30]  R. Hauer,et al.  Diagnosis and long-term follow-up of the Brugada syndrome in patients with idiopathic ventricular fibrillation. , 2000, European heart journal.

[31]  E. Behr,et al.  Sudden Cardiac Death With Autopsy Findings of Uncertain Significance: Potential for Erroneous Interpretation , 2013, Circulation. Arrhythmia and electrophysiology.

[32]  H. Tan,et al.  Active cascade screening in primary inherited arrhythmia syndromes: does it lead to prophylactic treatment? , 2010, Journal of the American College of Cardiology.

[33]  A Malliani,et al.  Electrical alternation of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome. , 1975, American heart journal.

[34]  Kyoung-Min Park,et al.  Mode of onset of ventricular fibrillation in patients with early repolarization pattern vs. Brugada syndrome. , 2010, European heart journal.

[35]  P. Lambiase,et al.  Prevalence of J-point elevation in sudden arrhythmic death syndrome families. , 2011, Journal of the American College of Cardiology.

[36]  Amos Katz,et al.  Distinguishing "benign" from "malignant early repolarization": the value of the ST-segment morphology. , 2012, Heart rhythm.

[37]  S. Priori,et al.  Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. , 2004, JAMA.

[38]  Eric Schulze-Bahr,et al.  Mutational spectrum in the Ca2+‐activated cation channel gene TRPM4 in patients with cardiac conductance disturbances , 2012, Human mutation.

[39]  A. Castellanos,et al.  Sudden cardiac death. Structure, function, and time-dependence of risk. , 1992, Circulation.

[40]  M. Gollob,et al.  The short QT syndrome: proposed diagnostic criteria. , 2011, Journal of the American College of Cardiology.

[41]  J. Brugada,et al.  Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. , 1992, Journal of the American College of Cardiology.

[42]  L. Jordaens,et al.  Who Are the Long-QT Syndrome Patients Who Receive an Implantable Cardioverter-Defibrillator and What Happens to Them?: Data From the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry , 2010, Circulation.

[43]  A. Wilde,et al.  A Novel Early Onset Lethal Form of Catecholaminergic Polymorphic Ventricular Tachycardia Maps to Chromosome 7p14‐p22 , 2007, Journal of cardiovascular electrophysiology.

[44]  Prashanthan Sanders,et al.  Mapping and Ablation of Ventricular Fibrillation Associated With Long-QT and Brugada Syndromes , 2003, Circulation.

[45]  E. Behr,et al.  Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families. , 2008, European heart journal.

[46]  Koji Maemura,et al.  Incidence and Prognostic Value of Early Repolarization Pattern in the 12-Lead Electrocardiogram , 2011, Circulation.

[47]  P. Coumel,et al.  KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. , 1997, Circulation.

[48]  G. Bonsel,et al.  Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy , 2008, European Journal of Human Genetics.

[49]  P. C. Viswanathan,et al.  A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. , 2003, The Journal of clinical investigation.

[50]  Michael J Ackerman,et al.  Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. , 2008, Heart rhythm.

[51]  C. Antzelevitch,et al.  Augmentation of J waves and electrical storms in patients with early repolarization. , 2008, The New England journal of medicine.

[52]  Carlo Napolitano,et al.  Erratum: Long QT syndrome patients with mutations on the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate: Implications for gene-specific therapy (Circulation (1995) 92 (3381-3386)) , 1996 .

[53]  S. Priori,et al.  Clinical Phenotype and Functional Characterization of CASQ2 Mutations Associated With Catecholaminergic Polymorphic Ventricular Tachycardia , 2006, Circulation.

[54]  John K Triedman,et al.  Implications of Implantable Cardioverter Defibrillator Therapy in Congenital Heart Disease and Pediatrics , 2004, Journal of cardiovascular electrophysiology.

[55]  P. Schwartz,et al.  NOS1AP Is a Genetic Modifier of the Long-QT Syndrome , 2009, Circulation.

[56]  Fabio Mosca,et al.  Prevalence of the Congenital Long-QT Syndrome , 2009, Circulation.

[57]  Ferhaan Ahmad,et al.  Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease. , 2008, Journal of molecular and cellular cardiology.

[58]  J. Graham.  Clinical Implications for Patients With Long QT Syndrome Who Experience a Cardiac Event During Infancy , 2010 .

[59]  S. Priori,et al.  [Risk stratification in Brugada syndrome]. , 2011, Giornale italiano di cardiologia.

[60]  S. Viskin,et al.  Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia. , 2007, Heart rhythm.

[61]  A. Wilde,et al.  High Distress in Parents Whose Children Undergo Predictive Testing for Long QT Syndrome , 2005, Public Health Genomics.

[62]  P. Coumel.  Catecholamine-induced severe ventricular arrhythmias with Adams-Stokes syndrome in children : report of four cases , 1978 .

[63]  Yun-Jiu Cheng,et al.  Early repolarization pattern and risk for arrhythmia death: a meta-analysis. , 2013, Journal of the American College of Cardiology.

[64]  Claudia Stöllberger,et al.  Guidelines for device-based therapy of cardiac rhythm abnormalities. , 2009, Heart rhythm.

[65]  K. Brown,et al.  Mutations of the Cardiac Ryanodine Receptor (RyR2) Gene in Familial Polymorphic Ventricular Tachycardia , 2001, Circulation.

[66]  E. Behr,et al.  Low prevalence of risk markers in cases of sudden death due to Brugada syndrome relevance to risk stratification in Brugada syndrome. , 2011, Journal of the American College of Cardiology.

[67]  M. Glikson,et al.  Outcome after implantation of cardioverter defibrillator [corrected] in patients with Brugada syndrome: a multicenter Israeli study (ISRABRU). , 2008, The Israel Medical Association journal : IMAJ.

[68]  S. Viskin,et al.  Management of Idiopathic Ventricular Fibrillation: Implantable Defibrillators? Antiarrhythmic Drugs? , 1998 .

[69]  Mark A Hlatky,et al.  ACC/AHA/HRS 2008 guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: executive summary. , 2008, Heart rhythm.

[70]  J. Brugada,et al.  Should patients with an asymptomatic Brugada electrocardiogram undergo pharmacological and electrophysiological testing? , 2005, Circulation.

[71]  A. Moss,et al.  Long QT Syndrome: An Indication for Cervicothoracic Sympathectomy , 1995, Cardiovascular surgery.

[72]  J. van den Bout,et al.  Can parents adjust to the idea that their child is at risk for a sudden death?: Psychological impact of risk for long QT syndrome , 2005, American journal of medical genetics. Part A.

[73]  J. Towbin,et al.  Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. , 2002, Human molecular genetics.

[74]  K. Aonuma,et al.  Successful catheter ablation of bidirectional ventricular premature contractions triggering ventricular fibrillation in catecholaminergic polymorphic ventricular tachycardia with RyR2 mutation. , 2012, Circulation. Arrhythmia and electrophysiology.

[75]  J. Jaspers,et al.  The influence of coping styles and perceived control on emotional distress in persons at risk for a hereditary heart disease , 2007, American journal of medical genetics. Part A.

[76]  Tuomas Kerola,et al.  Early Repolarization: Electrocardiographic Phenotypes Associated With Favorable Long-Term Outcome , 2011, Circulation.

[77]  S. Narayan,et al.  Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. , 2009, Journal of the American College of Cardiology.

[78]  S. Priori,et al.  Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. , 1998, Circulation.

[79]  M. Brignole,et al.  The Diagnosis and Management of Syncope , 2010, Current hypertension reports.

[80]  M. Sheppard,et al.  Aetiology of sudden cardiac death in athletes in the United Kingdom: a pathological study , 2009, Heart.

[81]  S. Priori,et al.  Magnetic resonance investigations in Brugada syndrome reveal unexpectedly high rate of structural abnormalities. , 2009, European Heart Journal.

[82]  M. Ackerman,et al.  Epinephrine QT Stress Testing in the Evaluation of Congenital Long-QT Syndrome: Diagnostic Accuracy of the Paradoxical QT Response , 2005, Circulation.

[83]  S. Priori,et al.  Association of Long QT Syndrome Loci and Cardiac Events Among Patients Treated With β-Blockers , 2004 .

[84]  P. Brugada,et al.  Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome. , 2007, European heart journal.

[85]  W. Shimizu.  Acquired forms of the Brugada syndrome. , 2005, Journal of electrocardiology.

[86]  S. Priori,et al.  Inherited calcium channelopathies in the pathophysiology of arrhythmias , 2012, Nature Reviews Cardiology.

[87]  S. Priori,et al.  Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. , 2004, Heart rhythm.

[88]  D. Lancet,et al.  A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. , 2001, Cold Spring Harbor symposia on quantitative biology.

[89]  A. Castellanos,et al.  Inferolateral early repolarization in athletes , 2011, Journal of Interventional Cardiac Electrophysiology.

[90]  F. Romeo,et al.  Distribution and prognostic significance of QT intervals in the lowest half centile in 12,012 apparently healthy persons. , 2006, The American journal of cardiology.

[91]  E. Behr,et al.  Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome , 2003, The Lancet.

[92]  Calum A MacRae,et al.  Risk stratification in the long-QT syndrome. , 2003, The New England journal of medicine.

[93]  A. Wilde,et al.  Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. , 2011, Journal of the American College of Cardiology.

[94]  D. Tamborero,et al.  Gender differences in clinical manifestations of Brugada syndrome. , 2008, Journal of the American College of Cardiology.

[95]  J. Brugada,et al.  Determinants of Sudden Cardiac Death in Individuals With the Electrocardiographic Pattern of Brugada Syndrome and No Previous Cardiac Arrest , 2003, Circulation.

[96]  J. Ornato,et al.  ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities. , 2008, Heart rhythm.

[97]  M. Yoshiyama,et al.  Successful radiofrequency catheter ablation for electrical storm of ventricular fibrillation in a patient with Brugada syndrome. , 2008, Circulation journal : official journal of the Japanese Circulation Society.

[98]  J. Brugada,et al.  Sudden Death Associated With Short-QT Syndrome Linked to Mutations in HERG , 2003, Circulation.

[99]  N. Hagiwara,et al.  Long-Term Prognosis of Probands With Brugada-Pattern ST-Elevation in Leads V1–V3 , 2009, Circulation. Arrhythmia and electrophysiology.

[100]  A. Zwinderman,et al.  Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study. , 2012, Journal of the American College of Cardiology.

[101]  Mohamed Chahine,et al.  SCN5A Polymorphism Restores Trafficking of a Brugada Syndrome Mutation on a Separate Gene , 2006, Circulation.

[102]  S. Viskin.  Implantable Cardioverter Defibrillator in High‐Risk Long QT Syndrome Patients , 2003, Journal of cardiovascular electrophysiology.

[103]  Charles Antzelevitch,et al.  J wave syndromes. , 2010, Heart rhythm.

[104]  H. Morita,et al.  Epicardial ablation eliminates ventricular arrhythmias in an experimental model of Brugada syndrome. , 2009, Heart rhythm.

[105]  Tohru Ohe,et al.  Fragmented QRS as a Marker of Conduction Abnormality and a Predictor of Prognosis of Brugada Syndrome , 2008, Circulation.

[106]  A. Wilde,et al.  Family and population strategies for screening and counselling of inherited cardiac arrhythmias , 2004, Annals of medicine.

[107]  Silvia G. Priori,et al.  Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need for definition and standardized clinical evaluation. Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the , 1997, Circulation.

[108]  G. Bonsel,et al.  Genetic counseling and cardiac care in predictively tested hypertrophic cardiomyopathy mutation carriers: The patients' perspective , 2009, American journal of medical genetics. Part A.

[109]  Lisa Pearse,et al.  Sudden Death in Young Adults: A 25-Year Review of Autopsies in Military Recruits , 2004, Annals of Internal Medicine.

[110]  Martin Borggrefe,et al.  Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. , 2010, Heart rhythm.

[111]  M. Sheppard,et al.  Sudden, unexpected cardiac or unexplained death in England: a national survey. , 2003, QJM : monthly journal of the Association of Physicians.

[112]  D. Roden,et al.  Common Sodium Channel Promoter Haplotype in Asian Subjects Underlies Variability in Cardiac Conduction , 2006, Circulation.

[113]  Carlo Napolitano,et al.  Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia , 2002, Circulation.

[114]  Carlo Napolitano,et al.  Risk stratification in the long-QT syndrome. , 2003, The New England journal of medicine.

[115]  W. Shimizu,et al.  Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization , 2011, Circulation. Arrhythmia and electrophysiology.

[116]  Michael Christiansen,et al.  Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. , 2012, American journal of human genetics.

[117]  D. Tester,et al.  The role of molecular autopsy in unexplained sudden cardiac death , 2006, Current opinion in cardiology.

[118]  S. Priori.  Arrhythmias: Unexplained sudden cardiac death—back to clinical evaluation , 2009, Nature Reviews Cardiology.

[119]  Thomas Lavergne,et al.  Sudden cardiac arrest associated with early repolarization. , 2008, The New England journal of medicine.

[120]  T. Ikeda,et al.  Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification. , 2001, Journal of the American College of Cardiology.

[121]  D. Coomans,et al.  The value of a family history of sudden death in patients with diagnostic type I Brugada ECG pattern. , 2011, European heart journal.

[122]  M. Borggrefe,et al.  Arrhythmias: A 'Schwartz score' for short QT syndrome , 2011, Nature Reviews Cardiology.

[123]  J. Towbin,et al.  Long-Term Follow-Up of Individuals With the Electrocardiographic Pattern of Right Bundle-Branch Block and ST-Segment Elevation in Precordial Leads V1 to V3 , 2002, Circulation.

[124]  G. Breithardt,et al.  Life-threatening Arrhythmias Genotype-phenotype Correlation in the Long-qt Syndrome : Gene-specific Triggers for Genotype-phenotype Correlation in the Long-qt Syndrome Gene-specific Triggers for Life-threatening Arrhythmias , 2022 .

[125]  M. Cárdenas,et al.  Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with an implantable cardioverter-defibrillator: a case series and literature review. , 2012, Heart rhythm.

[126]  H. Morita,et al.  Electroanatomical correlation of repolarization abnormalities in Brugada syndrome: detection of type 1 electrocardiogram in the right ventricular outflow tract. , 2010, Journal of the American College of Cardiology.

[127]  A. Waldo.  Prevalence and Prognostic Significance of Short QT Interval in a Middle-Aged Finnish Population , 2008 .

[128]  M. Tobin,et al.  Heritability of Early Repolarization: A Population-Based Study , 2011, Circulation. Cardiovascular genetics.

[129]  J. Brugada,et al.  Idiopathic Short QT Interval:A New Clinical Syndrome? , 2001, Cardiology.

[130]  A. Wilde,et al.  Absence of Calsequestrin 2 Causes Severe Forms of Catecholaminergic Polymorphic Ventricular Tachycardia , 2002, Circulation research.

[131]  A. Moss,et al.  Ranolazine Shortens Repolarization in Patients with Sustained Inward Sodium Current Due to Type‐3 Long‐QT Syndrome , 2008, Journal of cardiovascular electrophysiology.

[132]  J. Caldwell,et al.  The clinical management of relatives of young sudden unexplained death victims; implantable defibrillators are rarely indicated , 2012, Heart.

[133]  E. Behr,et al.  Sudden arrhythmic death syndrome: a national survey of sudden unexplained cardiac death , 2007, Heart.

[134]  D. Roden,et al.  Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans , 2009, Nature Medicine.

[135]  A. Moss,et al.  ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. , 1995, Circulation.

[136]  P. Schwartz,et al.  All LQT3 patients need an ICD: true or false? , 2009, Heart rhythm.

[137]  P. Coumel,et al.  Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. , 1995, Circulation.

[138]  M. Nagashima,et al.  Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death , 2003, Heart.

[139]  N. Saoudi,et al.  Radiofrequency Ablation of Ventricular Fibrillation and Multiple Right and Left Atrial Tachycardia in a Patient with Brugada Syndrome , 2004, Journal of Interventional Cardiac Electrophysiology.

[140]  A. Zwinderman,et al.  Therapeutic approach for patients with catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments. , 2012, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[141]  H. Crijns,et al.  Favourable outcome in idiopathic ventricular fibrillation with treatment aimed at prevention of high sympathetic tone and suppression of inducible arrhythmias. , 1995, British heart journal.

[142]  D. Lancet,et al.  A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. , 2001, American journal of human genetics.

[143]  R. N. Planken,et al.  SCN5A Mutations in Brugada Syndrome Are Associated with Increased Cardiac Dimensions and Reduced Contractility , 2012, PloS one.

[144]  Roger W Byard,et al.  Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. , 2004, Pediatrics.

[145]  Y. Kokubo,et al.  Sex Hormone and Gender Difference—Role of Testosterone on Male Predominance in Brugada Syndrome , 2007, Journal of cardiovascular electrophysiology.

[146]  S. Priori,et al.  Yield of Genetic Screening in Inherited Cardiac Channelopathies: How to Prioritize Access to Genetic Testing , 2009, Circulation. Arrhythmia and electrophysiology.

[147]  A. Wilde,et al.  Mechanisms of inherited cardiac conduction disease. , 2005, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[148]  K. Reinier,et al.  Population-based analysis of sudden death in children: The Oregon Sudden Unexpected Death Study. , 2009, Heart rhythm.

[149]  M. Gollob,et al.  A novel mutation in the RYR2 gene leading to catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation: dose-dependent arrhythmia-event suppression by β-blocker therapy. , 2011, The Canadian journal of cardiology.

[150]  J. Healey,et al.  Systematic Assessment of Patients With Unexplained Cardiac Arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER) , 2009, Circulation.

[151]  P. Schwartz,et al.  Left cardiac sympathetic denervation for the prevention of life-threatening arrhythmias: the surgical supraclavicular approach to cervicothoracic sympathectomy. , 2010, Heart rhythm.

[152]  Carlo Napolitano,et al.  A cardiac arrhythmia syndrome caused by loss of ankyrin-B function , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[153]  P. Schwartz,et al.  QTc behavior during exercise and genetic testing for the long-QT syndrome. , 2011, Circulation.

[154]  G. Eide,et al.  General anxiety, depression, and physical health in relation to symptoms of heart-focused anxiety- a cross sectional study among patients living with the risk of serious arrhythmias and sudden cardiac death , 2011, Health and quality of life outcomes.

[155]  M. P,et al.  Electrical Storms in Brugada Syndrome: Review of Pharmacologic and Ablative Therapeutic Options , 2005, Indian Pacing and Electrophysiology Journal.

[156]  H. Crijns,et al.  Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? , 2004, Journal of Molecular Medicine.

[157]  R. Hauer,et al.  Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. , 2012, Journal of the American College of Cardiology.

[158]  Andrew C. Zygmunt,et al.  Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males , 2002, Circulation.

[159]  M. Horie,et al.  Association of atrial arrhythmia and sinus node dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia. , 2007, Circulation journal : official journal of the Japanese Circulation Society.

[160]  J. Brugada,et al.  Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. , 1998, Circulation.

[161]  M. Bitner-Glindzicz,et al.  The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. , 2006, Circulation.

[162]  L. Mestroni,et al.  Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. , 2003, Journal of the American College of Cardiology.

[163]  L. Toivonen,et al.  Calcium Channel Antagonism Reduces Exercise‐Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations , 2005, Journal of cardiovascular electrophysiology.

[164]  F. Gaita,et al.  Risk stratification of the patients with Brugada type electrocardiogram: a community-based prospective study. , 2008, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[165]  C. Berul,et al.  Inherited Conduction System Abnormalities—One Group of Diseases, Many Genes , 2006, Journal of cardiovascular electrophysiology.

[166]  P. Schwartz,et al.  Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. , 1994, Journal of the American College of Cardiology.

[167]  M. Ackerman,et al.  Implantable cardioverter defibrillator therapy for congenital long QT syndrome: a single-center experience. , 2010, Heart rhythm.

[168]  Michael J Ackerman,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). , 2011, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[169]  H. Tan,et al.  Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. , 2009, Heart rhythm.

[170]  J. Lunardi,et al.  Germline and somatic mosaicism for a mutation of the ryanodine receptor type 2 gene: implication for genetic counselling and patient caring. , 2011, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[171]  G. Bonsel,et al.  Quality of life and psychological distress in hypertrophic cardiomyopathy mutation carriers: A cross‐sectional cohort study , 2009, American journal of medical genetics. Part A.

[172]  G. Landes,et al.  Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias , 1996, Nature Genetics.

[173]  S. Priori,et al.  High Efficacy of β-Blockers in Long-QT Syndrome Type 1: Contribution of Noncompliance and QT-Prolonging Drugs to the Occurrence of β-Blocker Treatment “Failures” , 2009, Circulation.

[174]  Derick R. Peterson,et al.  Increased Risk of Arrhythmic Events in Long-QT Syndrome With Mutations in the Pore Region of the Human Ether-a-go-go–Related Gene Potassium Channel , 2002, Circulation.

[175]  A. Moss,et al.  Unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome. , 1971, The New England journal of medicine.

[176]  V. Salomaa,et al.  The early repolarization pattern in the general population: clinical correlates and heritability. , 2011, Journal of the American College of Cardiology.

[177]  S. Priori,et al.  Left Cardiac Sympathetic Denervation in the Management of High-Risk Patients Affected by the Long-QT Syndrome , 2004, Circulation.

[178]  J. Schmid,et al.  Prevalence of long and short QT in a young population of 41,767 predominantly male Swiss conscripts. , 2009, Heart rhythm.

[179]  G. Bushman,et al.  The role of thoracic epidural blockade in predicting responsiveness to left sympathetic denervation in patients with catecholaminergic polymorphic ventricular tachycardia. , 2011, Journal of cardiothoracic and vascular anesthesia.

[180]  A. Moss,et al.  The Common Long-QT Syndrome Mutation KCNQ1/A341V Causes Unusually Severe Clinical Manifestations in Patients With Different Ethnic Backgrounds: Toward a Mutation-Specific Risk Stratification , 2007, Circulation.

[181]  Michael J Ackerman,et al.  Genotype-phenotype aspects of type 2 long QT syndrome. , 2009, Journal of the American College of Cardiology.

[182]  Euan Ashley,et al.  Early Repolarization in an Ambulatory Clinical Population , 2011, Circulation.

[183]  J. Healey,et al.  Derivation and Validation of a Simple Exercise-Based Algorithm for Prediction of Genetic Testing in Relatives of LQTS Probands , 2011, Circulation.

[184]  J. Svendsen,et al.  Nationwide study of sudden cardiac death in persons aged 1-35 years. , 2011, European heart journal.

[185]  谷山 真規子.  Atrial fibrillation in patients with Brugada syndrome : relationships of gene mutation, electrophysiology, and clinical backgrounds , 2008 .

[186]  Martin Borggrefe,et al.  Short QT Syndrome: A Familial Cause of Sudden Death , 2003, Circulation.

[187]  James H. Davis.  Sudden death in the young. , 2009, EMS magazine.

[188]  D. Fatkin,et al.  Guidelines for genetic testing of inherited cardiac disorders. , 2011, Heart, lung & circulation.

[189]  M. Ackerman,et al.  Competitive sports participation in athletes with congenital long QT syndrome. , 2012, JAMA.

[190]  Arthur J Moss,et al.  SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome , 1995, Cell.

[191]  T. Ikeda,et al.  Circadian variation of late potentials in idiopathic ventricular fibrillation associated with J waves: insights into alternative pathophysiology and risk stratification. , 2010, Heart rhythm.

[192]  S. Priori,et al.  Natural History of Brugada Syndrome: Insights for Risk Stratification and Management , 2002, Circulation.

[193]  Andrea Mazzanti,et al.  Long-term follow-up of patients with short QT syndrome. , 2011, Journal of the American College of Cardiology.

[194]  M. Ackerman,et al.  Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. , 2009, Heart rhythm.

[195]  W. Shimizu,et al.  Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy. , 2000, Journal of the American College of Cardiology.

[196]  M Borggrefe,et al.  Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome: Results From the FINGER Brugada Syndrome Registry , 2010, Circulation.

[197]  F. Charpentier,et al.  Progressive Cardiac Conduction Disease , 2008 .

[198]  S. Priori,et al.  Molecular Autopsy for Sudden Unexplained Death? Time to Discuss Pros and Cons , 2012, Journal of cardiovascular electrophysiology.

[199]  H. Heidbuchel,et al.  Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization role of drug therapy. , 2009, Journal of the American College of Cardiology.

[200]  A. Wilde,et al.  Sudden Unexplained Death: Heritability and Diagnostic Yield of Cardiological and Genetic Examination in Surviving Relatives , 2005, Circulation.

[201]  P. Rahko,et al.  Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy. , 2008, American heart journal.

[202]  W. Shimizu,et al.  Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada syndrome. , 2007, The American journal of cardiology.

[203]  S. Priori,et al.  Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. , 1995, Circulation.

[204]  A. Moss,et al.  Risk of fatal arrhythmic events in long QT syndrome patients after syncope. , 2010, Journal of the American College of Cardiology.

[205]  Distinguishing ‘benign’ from ‘malignant early repolarization’: the value of the ST-segment morphology , 2012 .

[206]  A. Peters,et al.  A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern. , 2012, Heart rhythm.

[207]  J. Brugada,et al.  Inferior and Lateral Electrocardiographic Repolarization Abnormalities in Brugada Syndrome , 2009, Circulation. Arrhythmia and electrophysiology.

[208]  Charles Antzelevitch.  Brugada syndrome. , 2006, Pacing and clinical electrophysiology : PACE.

[209]  A. Peters,et al.  Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA) , 2010, PLoS medicine.

[210]  Jay W Mason,et al.  Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. , 2007, Journal of electrocardiology.

[211]  Dan M. Roden,et al.  ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines , 2006 .

[212]  Tachapong Ngarmukos,et al.  Prevention of Ventricular Fibrillation Episodes in Brugada Syndrome by Catheter Ablation Over the Anterior Right Ventricular Outflow Tract Epicardium , 2011, Circulation.

[213]  S. Priori,et al.  A Novel Form of Short QT Syndrome (SQT3) Is Caused by a Mutation in the KCNJ2 Gene , 2005, Circulation research.

[214]  S. Viskin,et al.  J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. , 2008, Journal of the American College of Cardiology.

[215]  H. Katus,et al.  Successful acute and long-term management of electrical storm in Brugada syndrome using orciprenaline and quinine/quinidine , 2010, Clinical Research in Cardiology.

[216]  D. Nieman.  Aetiology of sudden cardiac death in athletes in the United Kingdom: a pathological study , 2010 .

[217]  I. V. van Langen,et al.  A Case of Catecholaminergic Polymorphic Ventricular Tachycardia Caused by Two Calsequestrin 2 Mutations , 2008, Pacing and clinical electrophysiology : PACE.

[218]  E. Kaufman,et al.  Mutations in Cytoplasmic Loops of the KCNQ1 Channel and the Risk of Life-Threatening Events: Implications for Mutation-Specific Response to &bgr;-Blocker Therapy in Type 1 Long-QT Syndrome , 2012, Circulation.

[219]  E. Kaufman,et al.  Risk of death in the long QT syndrome when a sibling has died. , 2008, Heart rhythm.

[220]  R. Hauer,et al.  Unexplained cardiac arrest. The need for a prospective registry. , 1992, European heart journal.

[221]  Michel Haïssaguerre,et al.  Loss-of-Function Mutations in the Cardiac Calcium Channel Underlie a New Clinical Entity Characterized by ST-Segment Elevation, Short QT Intervals, and Sudden Cardiac Death , 2007, Circulation.

[222]  Wataru Shimizu,et al.  Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. , 2010, Journal of the American College of Cardiology.

[223]  M. Hendriks,et al.  Familial disease with a risk of sudden death: a longitudinal study of the psychological consequences of predictive testing for long QT syndrome. , 2008, Heart rhythm.

[224]  S. Priori,et al.  CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism , 2004, Cell.

[225]  Jani T Tikkanen,et al.  Long-term outcome associated with early repolarization on electrocardiography. , 2009, The New England journal of medicine.

[226]  Lauri Toivonen,et al.  The Jervell and Lange-Nielsen Syndrome: Natural History, Molecular Basis, and Clinical Outcome , 2006, Archives des maladies du coeur et des vaisseaux.

[227]  A. Wilde,et al.  Ventricular Fibrillation with Prominent Early Repolarization Associated with a Rare Variant of KCNJ8/KATP Channel , 2009, Journal of cardiovascular electrophysiology.

[228]  Siobhan M. Dolan,et al.  Challenges of genetic testing in adolescents with cardiac arrhythmia syndromes , 2011, Journal of Medical Ethics.

[229]  P. Schwartz,et al.  Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. , 2008, The New England journal of medicine.

[230]  A. Leenhardt,et al.  Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human , 2012, Human molecular genetics.

[231]  H. Morita,et al.  Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. , 2002, Journal of the American College of Cardiology.

[232]  G. Breithardt,et al.  Atrial Arrhythmias in Long‐QT Syndrome under Daily Life Conditions: A Nested Case Control Study , 2009, Journal of cardiovascular electrophysiology.

[233]  M. Ackerman,et al.  The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. , 2011, Heart rhythm.

[234]  S. Priori,et al.  Mutations in the Cardiac Ryanodine Receptor Gene (hRyR2) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia , 2001, Circulation.

[235]  A. V. van Ginneken,et al.  Mutation in the KCNQ1 Gene Leading to the Short QT-Interval Syndrome , 2004, Circulation.

[236]  G. Breithardt,et al.  Long-Term Prognosis of Individuals With Right Precordial ST-Segment–Elevation Brugada Syndrome , 2005, Circulation.

[237]  K. Hayashi,et al.  Assessment of QT Intervals and Prevalence of Short QT Syndrome in Japan , 2008, Clinical cardiology.

[238]  Ravi B. Patel,et al.  Early Repolarization Associated With Ventricular Arrhythmias in Patients With Chronic Coronary Artery Disease , 2010, Circulation. Arrhythmia and electrophysiology.

[239]  P. Lambiase,et al.  Genetics and cardiovascular disease—causes and prevention of unexpected sudden adult death: the role of the SADS clinic , 2011, Heart.

[240]  Claudia Stöllberger,et al.  Guidelines for device-based therapy of cardiac rhythm abnormalities. , 2009, Heart rhythm.

[241]  J. Blanc,et al.  Guidelines for the diagnosis and management of syncope (version 2009). , 2009, European heart journal.

[242]  P. Schwartz,et al.  Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes. , 2010, Heart rhythm.

[243]  H. Kinney,et al.  Risk Factor Changes for Sudden Infant Death Syndrome After Initiation of Back-to-Sleep Campaign , 2012, Pediatrics.

[244]  A. Wilde,et al.  The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. , 2010, Journal of the American College of Cardiology.

[245]  M. O'Neill,et al.  Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome: A Multicenter Study , 2006, Circulation.

[246]  J. A. Gomes,et al.  Risk Stratification of Individuals with the Brugada Electrocardiogram: A Meta‐Analysis , 2006, Journal of cardiovascular electrophysiology.

[247]  C. Berul,et al.  Video-assisted thoracoscopic cardiac denervation: a potential novel therapeutic option for children with intractable ventricular arrhythmias. , 2008, The Annals of thoracic surgery.

[248]  A. Moss,et al.  Implantable Cardioverter Defibrillator in High‐Risk Long QT Syndrome Patients , 2003, Journal of cardiovascular electrophysiology.

[249]  M. Sheppard,et al.  Guidelines for autopsy investigation of sudden cardiac death , 2007, Virchows Archiv.

[250]  S. Priori,et al.  Should patients with an asymptomatic Brugada electrocardiogram undergo pharmacological and electrophysiological testing? , 2005, Circulation.

[251]  Michel Haissaguerre,et al.  Short QT syndrome: pharmacological treatment. , 2004, Journal of the American College of Cardiology.

[252]  L. McLain,et al.  Sudden death in young athletes. , 2003, Pediatric annals.

[253]  L. Yeates,et al.  The emerging role of the cardiac genetic counselor. , 2011, Heart Rhythm.

[254]  W. Shimizu,et al.  Clinical impact of the number of extrastimuli in programmed electrical stimulation in patients with Brugada type 1 electrocardiogram. , 2012, Heart rhythm.