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European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases

. 2022 Aug ; 38 (4) : 491-553. [epub] 20220531

Status PubMed-not-MEDLINE Language English Country Japan Media electronic-ecollection

Document type Journal Article

Grant support
MC_UP_1102/20 Medical Research Council - United Kingdom

Agnes Ginges Centre for Molecular Cardiology at Centenary Institute University of Sydney Sydney Australia

Amsterdam UMC Heart Center Department of Experimental Cardiology Amsterdam The Netherlands

Arrhythmia and Electrophysiology Unit Biocor Institute Minas Gerais Brazil

Arrhythmia Unit Instituto do Coracao Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Sao Paulo Brazil

Arrhythmia Unit Instituto do Coração Hospital das Clínicas HCFMUSP Faculdade de Medicina Universidade de São Paulo São Paulo Brazil

Cardiac Arrhythmia Service Massachusetts General Hospital and Harvard Medical School Boston MA USA

Cardiac Wellness Institute Chennai India

Cardiomyopathy Unit and Cardiac Rehabilitation Unit San Luca Hospital Istituto Auxologico Italiano IRCCS Milan Italy

Cardiovascular Clinical Academic Group Institute of Molecular and Clinical Sciences St George's University of London; St George's University Hospitals NHS Foundation Trust London UKMayo Clinic HealthcareLondon

Cardiovascular Genetics Center Department of Medicine Montreal Heart Institute Université de Montréal Montreal Canada

Cardiovascular Health Research Unit Division of Cardiology Department of Medicine University of Washington Seattle WA USA

Cardiovascular Research Lankenau Institute of Medical Research Wynnewood PA USA

Center for Cardiac Arrhythmias of Genetic Origin Istituto Auxologico Italiano IRCCS Milan Italy

Center for Cardiac Electrophysiology and Pacing University Hospitals Cleveland Medical Center Case Western Reserve University School of Medicine Cleveland OH USA

Center for Human Genetics University Hospitals Leuven Leuven Belgium

Centro de Investigacion Biomedica en Red en Enfermedades Cariovasculares Madrid Spain

Centro Nacional de Investigaciones Cardiovasculares Carlos 3 Madrid Spain

Cincinnati Children's Hospital Medical Centre University of Cincinnati Cincinnati OH USA

Clinical Department Health in Code A Coruña Spain

Department of Bioscience and Genetics National Cerebral and Cardiovascular Center Suita Japan

Department of Cardiology and Intensive Care Medicine University Hospital Campus Klinikum Bielefeld Bielefeld Germany

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Cardiovascular Medicine Division of Heart Rhythm Services Windland Smith Rice Genetic Heart Rhythm Clinic Mayo Clinic Rochester MN USA

Department of Cardiovascular Medicine Graduate School of Medicine Tokyo Japan

Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA

Department of Cardiovascular Medicine Stanford University Stanford CA USA

Department of Cardiovascular Medicine The 2nd Affiliated Hospital of Nanchang University Nanchang China

Department of Clinical Laboratory Medicine and Genetics National Cerebral and Cardiovascular Center Suita Osaka Japan

Department of Electrophysiology Heart Center at University of Leipzig Leipzig Germany

Department of Electrophysiology Heart Center Leipzig at University of Leipzig Leipzig Germany

Department of Medicine and Surgery University of Milano Bicocca Milan Italy

Department of Molecular Medicine University of Pavia Pavia Italy

Department of Pediatrics Division of Cardiology Vanderbilt University School of Medicine Nashville TN USA

Departments of Cardiovascular Medicine Pediatric and Adolescent Medicine and Molecular Pharmacology and Experimental Therapeutics; Divisions of Heart Rhythm Services and Pediatric Cardiology; Windland Smith Rice Genetic Heart Rhythm Clinic and Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic Rochester MN USA

Division of Cardiology Department of Internal Medicine Korea University Anam Hospital Korea University College of Medicine Seoul Republic of Korea

Division of Cardiology University of British Columbia Vancouver Canada

Division of Pediatric Arrhythmia and Electrophysiology Italian Hospital of Buenos Aires Buenos Aires Argentina

Heart Center Bad Neustadt Bad Neustadt a d Saale Germany

Heart Centre Department of Cardiology Amsterdam Universitair Medische Centra Amsterdam The Netherlands

Heart Failure and Inherited Cardiac Diseases Unit Department of Cardiology Hospital Universitario Puerta de Hierro Madrid Spain

Hipercol Brasil Program São Paulo Brazil

Inherited Arrhythmia and Cardiomyopathy Program Division of Cardiology University of Toronto Toronto ON Canada

Institut d'Investigacions Biomèdiques August Pi Sunyer Madrid Spain

Institute for Genetics of Heart Diseases University Hospital Münster Münster Germany

Instituto Nacional de Cardiología Ignacio Chávez Ciudad de México Mexico

Laboratory of Genetics and Molecular Cardiology Heart Institute University of São Paulo Medical School São Paulo Brazil

Leipzig Heart Institute Leipzig Germany

Metrohealth Medical Center Case Western Reserve University Cleveland OH USA

Molecular Cardiology Istituti Clinici Scientifici Maugeri IRCCS Pavia Italy

National Cerebral and Cardiovascular Center Research Institute Suita Japan

National Heart and Lung Institute and MRC London Institute of Medical Sciences Imperial College London London UK

Royal Brompton and Harefield Hospitals Guy's and St Thomas' NHS Foundation Trust London UK

Sorbonne Université Centre Paris France

Sydney Childrens Hospital Network University of Sydney Sydney Australia

The Department of Cardiology the Heart Centre Copenhagen University Hospital Rigshopitalet Copenhagen Denmark; Section of genetics Department of Forensic Medicine Faculty of Medical Sciences University of Copenhagen Denmark

See more in PubMed

Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H et al; European Heart Rhythm Association (EHRA). 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 2011;13:1077–109. PubMed

Schwartz PJ, Crotti L, George AL Jr. Modifier genes for sudden cardiac death. Eur Heart J. 2018;39:3925–31. PubMed PMC

Walsh R, Tadros R, Bezzina CR. When genetic burden reaches threshold. Eur Heart J. 2020;41:3849–55. PubMed PMC

Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. Genome‐wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50:1219–24. PubMed PMC

Schwartz PJ, Breithardt G, Howard AJ, Julian DG, Rehnqvist AN. Task Force Report: the legal implications of medical guidelines—a Task Force of the European Society of Cardiology. Eur Heart J. 1999;20:1152–7. PubMed

Stiles MK, Wilde AAM, Abrams DJ, Ackerman MJ, Albert CM, Behr ER, et al. 2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families. Heart Rhythm. 2021;18:e1–50. PubMed PMC

Cronin EM, Bogun FM, Maury P, Peichl P, Chen M, Namboodiri N, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias: executive summary. J Arrhythm. 2020;36:1–58. PubMed PMC

Musunuru K, Hershberger RE, Day SM, Klinedinst NJ, Landstrom AP, Parikh VN et al; American Heart Association Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology Genetic testing for inherited cardiovascular diseases: a scientific statement from the American Heart Association. Circ Genom Precis Med 2020;13:e000067. PubMed

Fellmann F, van El CG, Charron P , Michaud K, Howard HC, Boers SN et al; on behalf of European Society of Human Genetics, European Council of Legal Medicine, European Society of Cardiology working group on myocardial and pericardial diseases, European Reference Network for rare, low prevalence and complex diseases of the heart (ERN GUARD‐Heart), Association for European Cardiovascular Pathology . European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death. Eur J Hum Genet 2019;27:1763–73. PubMed PMC

Ingles J, Goldstein J, Thaxton C, Caleshu C, Corty EW, Crowley SB, et al. Evaluating the clinical validity of hypertrophic cardiomyopathy genes. Circ Genom Precis Med. 2019;12:e002460. PubMed PMC

Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: executive summary. Heart Rhythm. 2019;16:e373–407. PubMed

Al‐Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2018;15:e190–252. PubMed

Priori SG, Blomström‐Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36:2793–867. PubMed

Pedersen CT, Kay GN, Kalman J, Borggrefe M, Della‐Bella P, Dickfeld T et al; EP‐Europace,UK. EHRA/HRS/APHRS expert consensus on ventricular arrhythmias. Heart Rhythm 2014;11:e166–96. PubMed

Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. 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. Heart Rhythm. 2013;10:1932–63. PubMed

Charron P, Arad M, Arbustini E, Basso C, Bilinska Z, Elliott P, et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2010;31:2715–26. PubMed

Walsh R, Adler A, Amin AS, Abiusi E, Care M, Bikker H, et al. A multi‐centred, evidence‐based evaluation of gene validity in sudden arrhythmic death syndromes: CPVT and the short QT syndrome. Eur Heart J 2021;doi:10.1093/eurheartj/ehab687. PubMed PMC

James CA, Jongbloed JDH, Hershberger RE, Morales A, Judge DP, Syrris P, et al. International evidence based reappraisal of genes associated with arrhythmogenic right ventricular cardiomyopathy using the clinical genome resource framework. Circ Genom Precis Med 2021;14:e003273. PubMed PMC

Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, et al. Evidence‐based assessment of genes in dilated cardiomyopathy. Circulation. 2021;144:7–19. PubMed PMC

Adler A, Novelli V, Amin AS, Abiusi E, Care M, Nannenberg EA, et al. An international, multicentered, evidence‐based reappraisal of genes reported to cause congenital long QT syndrome. Circulation. 2020;141:418–28. PubMed PMC

Hosseini SM, Kim R, Udupa S, Costain G, Jobling R, Liston E et al; National Institutes of Health Clinical Genome Resource Consortium. Reappraisal of reported genes for sudden arrhythmic death: evidence‐based evaluation of gene validity for Brugada syndrome. Circulation 2018;138:1195–205. PubMed PMC

Mont L, Pelliccia A, Sharma S, Biffi A, Borjesson MB, Terradellas J. et al; Reviewers. Pre‐participation cardiovascular evaluation for athletic participants to prevent sudden death: position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE. Eur J Prev Cardiol. 2017;24:41–69. PubMed

Claussnitzer M, Cho JH, Collins R, Cox NJ, Dermitzakis ET, Hurles ME, et al. A brief history of human disease genetics. Nature. 2020;577:179–89. PubMed PMC

Roberts R, Marian AJ, Dandona S, Stewart AF. Genomics in cardiovascular disease. J Am Coll Cardiol. 2013;61:2029–37. PubMed PMC

Kim L, Devereux RB, Basson CT. Impact of genetic insights into mendelian disease on cardiovascular clinical practice. Circulation. 2011;123:544–50. PubMed

Wordsworth S, Leal J, Blair E, Legood R, Thomson K, Seller A, et al. DNA testing for hypertrophic cardiomyopathy: a cost‐effectiveness model. Eur Heart J. 2010;31:926–35. PubMed

Wilde AA, Behr ER. Genetic testing for inherited cardiac disease. Nat Rev Cardiol. 2013;10:571–83. PubMed

Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, et al. Transethnic genome‐wide association study provides insights in the genetic architecture and heritability of long QT syndrome. Circulation. 2020;142:324–38. PubMed PMC

Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, et al. Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect. Nat Genet. 2021;53:128–34. PubMed PMC

Harper AR, Goel A, Grace C, Thomson KL, Petersen SE, Xu X, et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. Nat Genet. 2021;53:135–42. PubMed PMC

Conrad DF, Keebler JE, DePristo MA, Lindsay SJ, Zhang Y, Casals F et al; 1000 Genomes Project . Variation in genome‐wide mutation rates within and between human families. Nat Genet 2011;43:712–4. PubMed PMC

Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA et al; 1000 Genomes Project Consortium . A map of human genome variation from population‐scale sequencing. Nature 2010;467:1061–73. PubMed PMC

Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280–91. PubMed

Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N, et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science. 2007;315:848–53. PubMed PMC

Zhang F, Gu W, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet. 2009;10:451–81. PubMed PMC

Lejeune J, Gautier M, Turpin R. Study of somatic chromosomes from 9 mongoloid children. C R Hebd Seances Acad Sci. 1959;248:1721–2. PubMed

Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain‐terminating inhibitors. Proc Natl Acad Sci USA. 1977;74:5463–7. PubMed PMC

International Human Genome Sequencing Consortium . Finishing the euchromatic sequence of the human genome. Nature. 2004;431:931–45. PubMed

Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, et al. Genome sequencing in microfabricated high‐density picolitre reactors. Nature. 2005;437:376–80. PubMed PMC

Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008;456:53–9. PubMed PMC

Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA. 2009;106:19096–101. PubMed PMC

Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461:272–6. PubMed PMC

Zhang F, Lupski JR. Non‐coding genetic variants in human disease. Hum Mol Genet. 2015;24:R102–10. PubMed PMC

Whiffin N, Karczewski KJ, Zhang X, Chothani S, Smith MJ, Evans DG et al; Genome Aggregation Database Consortium. Characterising the loss‐of‐function impact of 5' untranslated region variants in 15,708 individuals. Nat Commun 2020;11:2523. PubMed PMC

Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, et al. Multi‐platform discovery of haplotype‐resolved structural variation in human genomes. Nat Commun. 2019;10:1784. PubMed PMC

Alkan C, Coe BP, Eichler EE. Genome structural variation discovery and genotyping. Nat Rev Genet. 2011;12:363–76. PubMed PMC

Hindson CM, Chevillet JR, Briggs HA, Gallichotte EN, Ruf IK, Hindson BJ, et al. Absolute quantification by droplet digital PCR versus analog real‐time PCR. Nat Methods. 2013;10:1003–5. PubMed PMC

LaFramboise T. Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances. Nucleic Acids Res. 2009;37:4181–93. PubMed PMC

Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19:249–55. PubMed

Miller DT, Lee K, Chung WK, Gordon AS, Herman GE, Klein TE et al; ACMG Secondary Findings Working Group . ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2021;23:1381–90. PubMed

Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA, et al. 10 years of GWAS discovery: biology, function, and translation. Am J Hum Genet. 2017;101:5–22. PubMed PMC

Pe'er I, Yelensky R, Altshuler D, Daly MJ. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol. 2008;32:381–5. PubMed

Sotoodehnia N, Isaacs A, de Bakker PI, Dorr M, Newton‐Cheh C, Nolte IM, et al. Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nat Genet. 2010;42:1068–76. PubMed PMC

Aung N, Vargas JD, Yang C, Cabrera CP, Warren HR, Fung K, et al. Genome‐wide analysis of left ventricular image‐derived phenotypes identifies fourteen loci associated with cardiac morphogenesis and heart failure development. Circulation. 2019;140:1318–30. PubMed PMC

Giri A, Hellwege JN, Keaton JM, Park J, Qiu C, Warren HR, et al. Trans‐ethnic association study of blood pressure determinants in over 750,000 individuals. Nat Genet. 2019;51:51–62. PubMed PMC

Nikpay M, Goel A, Won HH, Hall LM, Willenborg C, Kanoni S, et al. A comprehensive 1,000 Genomes‐based genome‐wide association meta‐analysis of coronary artery disease. Nat Genet. 2015;47:1121–30. PubMed PMC

Shah S, Henry A, Roselli C, Lin H, Sveinbjornsson G, Fatemifar G et al; Regeneron Genetics Center . Genome‐wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure; Nat Commun 2020;11:163. PubMed PMC

Roselli C, Chaffin MD, Weng LC, Aeschbacher S, Ahlberg G, Albert CM, et al. Multi‐ethnic genome‐wide association study for atrial fibrillation. Nat Genet. 2018;50:1225–33. PubMed PMC

Ashar FN, Mitchell RN, Albert CM, Newton‐Cheh C, Brody JA, Muller‐Nurasyid M, et al. A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. Eur Heart J. 2018;39:3961–9. PubMed PMC

Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, et al. Common variants at PubMed PMC

Villard E, Perret C, Gary F, Proust C, Dilanian G, Hengstenberg C, et al. A genome‐wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy. Eur Heart J. 2011;32:1065–76. PubMed PMC

Lambert SA, Gil L, Jupp S, Ritchie SC, Xu Y, Buniello A, et al. The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation. Nat Genet. 2021;53:420–5. PubMed PMC

Marston NA, Kamanu FK, Nordio F, Gurmu Y, Roselli C, Sever PS, et al. Predicting benefit from evolocumab therapy in patients with atherosclerotic disease using a genetic risk score: results from the FOURIER trial. Circulation. 2020;141:616–23. PubMed PMC

Damask A, Steg PG, Schwartz GG, Szarek M, Hagstrom E, Badimon L, et al. Patients with high genome‐wide polygenic risk scores for coronary artery disease may receive greater clinical benefit from alirocumab treatment in the ODYSSEY OUTCOMES trial. Circulation. 2020;141:624–36. PubMed

Marston NA, Gurmu Y, Melloni GEM, Bonaca M, Gencer B, Sever PS, et al. The effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibition on the risk of venous thromboembolism. Circulation. 2020;141:1600–7. PubMed PMC

Tadros R, Tan HL, El Mathari S, Kors JA, Postema PG, Lahrouchi N, et al. Predicting cardiac electrical response to sodium‐channel blockade and Brugada syndrome using polygenic risk scores. Eur Heart J. 2019;40:3097–107. PubMed PMC

Wijeyeratne YD, Tanck MW, Mizusawa Y, Batchvarov V, Barc J, Crotti L, et al. PubMed PMC

Turkowski KL, Dotzler SM, Tester DJ, Giudicessi JR, Bos JM, Speziale AD, et al. Corrected QT interval‐polygenic risk score and its contribution to type 1, type 2, and type 3 long‐QT syndrome in probands and genotype‐positive family members. Circ Genom Precis Med. 2020;13:e002922. PubMed

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier‐Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24. PubMed PMC

Manrai AK, Funke BH, Rehm HL, Olesen MS, Maron BA, Szolovits P, et al. Genetic misdiagnoses and the potential for health disparities. N Engl J Med. 2016;375:655–65. PubMed PMC

Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME. Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc. 2003;78:1479–87. PubMed

Ackerman MJ, Splawski I, Makielski JC, Tester DJ, Will ML, Timothy KW, et al. Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing. Heart Rhythm. 2004;1:600–7. PubMed

Giudicessi JR, Roden DM, Wilde AAM, Ackerman MJ. Classification and reporting of potentially proarrhythmic common genetic variation in long QT syndrome genetic testing. Circulation. 2018;137:619–30. PubMed PMC

Giudicessi JR, Wilde AAM, Ackerman MJ. The genetic architecture of long QT syndrome: a critical reappraisal. Trends Cardiovasc Med. 2018;28:453–64. PubMed PMC

Ackerman JP, Bartos DC, Kapplinger JD, Tester DJ, Delisle BP, Ackerman MJ. The Promise and Peril of Precision Medicine. Mayo Clin Proc. 2016;91:1606–16. PubMed PMC

Kelly MA, Caleshu C, Morales A, Buchan J, Wolf Z, Harrison SM, et al. Adaptation and validation of the ACMG/AMP variant classification framework for MYH7‐associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel. Genet Med. 2018;20:351–9. PubMed PMC

Richmond CM, James PA, Pantaleo SJ, Chong B, Lunke S, Tan TY, et al. Clinical and laboratory reporting impact of ACMG‐AMP and modified ClinGen variant classification frameworks in MYH7‐related cardiomyopathy. Genet Med. 2021;23:1108–15. PubMed

Bains S, Dotzler SM, Krijger C, Giudicessi JR, Ye D, Bikker H, et al. A phenotype‐enhanced variant classification framework to decrease the burden of missense variants of uncertain significance in type 1 long QT syndrome. Heart Rhythm. 2022;19:435–42. PubMed

Kim YE, Ki CS, Jang MA. Challenges and considerations in sequence variant interpretation for mendelian disorders. Ann Lab Med. 2019;39:421–9. PubMed PMC

Gelb BD, Cavé H, Dillon MW, Gripp KW, Lee JA, Mason‐Suares H et al; ClinGen RASopathy Working Group. ClinGen's RASopathy Expert Panel consensus methods for variant interpretation. Genet Med 2018;20:1334–45. PubMed PMC

Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60:705–15. PubMed

Lafreniere‐Roula M, Bolkier Y, Zahavich L, Mathew J, George K, Wilson J, et al. Family screening for hypertrophic cardiomyopathy: is it time to change practice guidelines? Eur Heart J. 2019;40:3672–81. PubMed PMC

Ingles J, Burns C, Funke B. Pathogenicity of hypertrophic cardiomyopathy variants: a path forward together. Circ Cardiovasc Genet. 2017;10:e001916. PubMed

Ouellette AC, Mathew J, Manickaraj AK, Manase G, Zahavich L, Wilson J, et al. Clinical genetic testing in pediatric cardiomyopathy: is bigger better? Clin Genet. 2018;93:33–40. PubMed

Jensen MK, Havndrup O, Christiansen M, Andersen PS, Diness B, Axelsson A, et al. Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12‐year follow‐up study of clinical screening and predictive genetic testing. Circulation. 2013;127:48–54. PubMed

Semsarian C, Ingles J, Wilde AA. Sudden cardiac death in the young: the molecular autopsy and a practical approach to surviving relatives. Eur Heart J. 2015;36:1290–6. PubMed

Rueda M, Wagner JL, Phillips TC, Topol SE, Muse ED, Lucas JR, et al. Molecular autopsy for sudden death in the young: is data aggregation the key? Front Cardiovasc Med. 2017;4:72. PubMed PMC

Torkamani A, Muse ED, Spencer EG, Rueda M, Wagner GN, Lucas JR, et al. Molecular autopsy for sudden unexpected death. JAMA. 2016;316:1492–4. PubMed PMC

Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119:19–31. PubMed

Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, et al. Calmodulin mutations associated with recurrent cardiac arrest in infants. Circulation. 2013;127:1009–17. PubMed PMC

Crotti L, Spazzolini C, Tester DJ, Ghidoni A, Baruteau AE, Beckmann BM, et al. Calmodulin mutations and life‐threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry. Eur Heart J. 2019;40:2964–75. PubMed PMC

Altmann HM, Tester DJ, Will ML, Middha S, Evans JM, Eckloff BW, et al. Homozygous/compound heterozygous triadin mutations associated with autosomal‐recessive long‐QT syndrome and pediatric sudden cardiac arrest: elucidation of the Triadin knockout syndrome. Circulation. 2015;131:2051–60. PubMed

Clemens DJ, Tester DJ, Giudicessi JR, Bos JM, Rohatgi RK, Abrams DJ, et al. International Triadin knockout syndrome registry. Circ Genom Precis Med 2019;12:e002419. PubMed

Itoh H, Crotti L, Aiba T, Spazzolini C, Denjoy I, Fressart V, et al. The genetics underlying acquired long QT syndrome: impact for genetic screening. Eur Heart J. 2016;37:1456–64. PubMed PMC

Shimizu W, Horie M. Phenotypic manifestations of mutations in genes encoding subunits of cardiac potassium channels. Circ Res. 2011;109:97–109. PubMed

Crotti L, Odening KE, Sanguinetti MC. Heritable arrhythmias associated with abnormal function of cardiac potassium channels. Cardiovasc Res. 2020;116:1542–56. PubMed

Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Arch Mal Coeur Vaiss. 1966;59:263–72. PubMed

Viskin S. Long QT syndromes and torsade de pointes. Lancet 1999;354:1625–33. PubMed

Takenaka K, Ai T, Shimizu W, Kobori A, Ninomiya T, Otani H, et al. Exercise stress test amplifies genotype‐phenotype correlation in the LQT1 and LQT2 forms of the long‐QT syndrome. Circulation. 2003;107:838–44. PubMed

Sy RW, van der Werf C, Chattha IS, Chockalingam P, Adler A, Healey JS, et al. Derivation and validation of a simple exercise‐based algorithm for prediction of genetic testing in relatives of LQTS probands. Circulation. 2011;124:2187–94. PubMed

Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long‐QT syndrome. Circulation. 2011;124:2181–4. PubMed

Schwartz PJ, Stramba‐Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, et al. Prevalence of the congenital long‐QT syndrome. Circulation. 2009;120:1761–7. PubMed PMC

Moss AJ, Schwartz PJ, Crampton RS, Locati E, Carleen E. The long QT syndrome: a prospective international study. Circulation. 1985;71:17–21. PubMed

Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J. 1985;109:399–411. PubMed

Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, et al. The Jervell and Lange‐Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation. 2006;113:783–90. PubMed

Roberts JD, Asaki SY, Mazzanti A, Bos JM, Tuleta I, Muir AR, et al. An international multicenter evaluation of type 5 long QT syndrome: a low penetrant primary arrhythmic condition. Circulation. 2020;141:429–39. PubMed PMC

Mazzanti A, Guz D, Trancuccio A, Pagan E, Kukavica D, Chargeishvili T, et al. Natural history and risk stratification in Andersen‐Tawil syndrome type 1. J Am Coll Cardiol. 2020;75:1772–84. PubMed

Wang DW, Crotti L, Shimizu W, Pedrazzini M, Cantu FD, Filippo P, et al. Malignant perinatal variant of long‐QT syndrome caused by a profoundly dysfunctional cardiac sodium channel. Circ Arrhythm Electrophysiol. 2008;1:370–8. PubMed PMC

Crotti L, Ghidoni A, Insolia R, Schwartz PJ. The role of the cardiac sodium channel in perinatal early infant mortality. Card Electrophysiol Clin. 2014;6:749–59.

Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, et al. The E1784K mutation in PubMed PMC

Rocchetti M, Sala L, Dreizehnter L, Crotti L, Sinnecker D, Mura M, et al. Elucidating arrhythmogenic mechanisms of long‐QT syndrome CALM1‐F142L mutation in patient‐specific induced pluripotent stem cell‐derived cardiomyocytes. Cardiovasc Res. 2017;113:531–41. PubMed

Schwartz PJ, Ackerman MJ, Antzelevitch C, Bezzina CR, Borggrefe M, Cuneo BF, et al. Inherited cardiac arrhythmias. Nat Rev Dis Primers. 2020;6:58. PubMed PMC

Dagradi F, Spazzolini C, Castelletti S, Pedrazzini M, Kotta MC, Crotti L, et al. Exercise training‐induced repolarization abnormalities masquerading as congenital long QT syndrome. Circulation. 2020;142:2405–15. PubMed

Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long‐QT syndrome: clinical impact. Circulation. 1999;99:529–33. PubMed

Shimizu W, Noda T, Takaki H, Kurita T, Nagaya N, Satomi K, et al. Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long‐QT syndrome. J Am Coll Cardiol. 2003;41:633–42. PubMed

Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S, et al. Risk for life‐threatening cardiac events in patients with genotype‐confirmed long‐QT syndrome and normal‐range corrected QT intervals. J Am Coll Cardiol. 2011;57:51–9. PubMed PMC

Mazzanti A, Maragna R, Vacanti G, Monteforte N, Bloise R, Marino M, et al. Interplay between genetic substrate, QTc duration, and arrhythmia risk in patients with long QT syndrome. J Am Coll Cardiol. 2018;71:1663–71. PubMed

Shimizu W, Moss AJ, Wilde AA, Towbin JA, Ackerman MJ, January CT, et al. Genotype‐phenotype aspects of type 2 long QT syndrome. J Am Coll Cardiol. 2009;54:2052–62. PubMed PMC

Schwartz PJ, Moreno C, Kotta MC, Pedrazzini M, Crotti L, Dagradi F, et al. Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region. Eur Heart J. 2021;42:4743–55. PubMed PMC

Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, et al. Clinical aspects of type‐1 long‐QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007;115:2481–9. PubMed PMC

Crotti L, Spazzolini C, Schwartz PJ, Shimizu W, Denjoy I, Schulze‐Bahr E, 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. Circulation. 2007;116:2366–75. PubMed

Wilde AA, Moss AJ, Kaufman ES, Shimizu W, Peterson DR, Benhorin J, et al. Clinical aspects of type 3 long‐QT syndrome: an International Multicenter Study. Circulation. 2016;134:872–82. PubMed PMC

Lee YK, Sala L, Mura M, Rocchetti M, Pedrazzini M, Ran X, et al. MTMR4 SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes. Cardiovasc Res. 2021;117:767–79. PubMed PMC

Vincent GM, Schwartz PJ, Denjoy I, Swan H, Bithell C, Spazzolini C, et al. High efficacy of beta‐blockers in long‐QT syndrome type 1: contribution of noncompliance and QT‐prolonging drugs to the occurrence of beta‐blocker treatment “failures”. Circulation. 2009;119:215–21. PubMed

Barsheshet A, Goldenberg I, O‐Uchi J, Moss AJ, Jons C, Shimizu W, et al. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life‐threatening events: implications for mutation‐specific response to beta‐blocker therapy in type 1 long‐QT syndrome. Circulation. 2012;125:1988–96. PubMed PMC

Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, et al. Left cardiac sympathetic denervation in the management of high‐risk patients affected by the long‐QT syndrome. Circulation. 2004;109:1826–33. PubMed

Dusi V, Pugliese L, De Ferrari GM, Odero A, Crotti L, Dagradi F, et al. Left cardiac sympathetic denervation for long QT syndrome: 50 years’ experience provides guidance for management. JACC Clin Electrophysiol 2021;https://doi.org/10.1016/j.jacep.2021.09.002. PubMed

Etheridge SP, Compton SJ, Tristani‐Firouzi M, Mason JW. A new oral therapy for long QT syndrome: long‐term oral potassium improves repolarization in patients with HERG mutations. J Am Coll Cardiol. 2003;42:1777–82. PubMed

Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, et al. Genotype‐phenotype correlation in the long‐QT syndrome: gene‐specific triggers for life‐threatening arrhythmias. Circulation. 2001;103:89–95. PubMed

Wilde AA, Jongbloed RJ, Doevendans PA, Düren DR, Hauer RN, van Langen IM, et al. Auditory stimuli as a trigger for arrhythmic events differentiate HERG‐related (LQTS2) patients from KVLQT1‐related patients (LQTS1). J Am Coll Cardiol. 1999;33:327–32. PubMed

Khositseth A, Tester DJ, Will ML, Bell CM, Ackerman MJ. Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. Heart Rhythm. 2004;1:60–4. PubMed

Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA, et al. Long QT syndrome patients with mutations of the PubMed

Mazzanti A, Maragna R, Faragli A, Monteforte N, Bloise R, Memmi M, et al. Gene‐specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol. 2016;67:1053–8. PubMed PMC

Funasako M, Aiba T, Ishibashi K, Nakajima I, Miyamoto K, Inoue Y, et al. Pronounced shortening of QT interval with mexiletine infusion test in patients with type 3 congenital long QT syndrome. Circ J. 2016;80:340–5. PubMed

Bos JM, Crotti L, Rohatgi RK, Castelletti S, Dagradi F, Schwartz PJ, et al. Mexiletine shortens the QT interval in patients with potassium channel‐mediated type 2 long QT syndrome. Circ Arrhythm Electrophysiol. 2019;12:e007280. PubMed

Mehta A, Ramachandra CJA, Singh P, Chitre A, Lua CH, Mura M, et al. Identification of a targeted and testable antiarrhythmic therapy for long‐QT syndrome type 2 using a patient‐specific cellular model. Eur Heart J. 2018;39:1446–55. PubMed

Schwartz PJ, Gnecchi M, Dagradi F, Castelletti S, Parati G, Spazzolini C, et al. From patient‐specific induced pluripotent stem cells to clinical translation in long QT syndrome Type 2. Eur Heart J. 2019;40:1832–6. PubMed

Schwartz PJ, Woosley RL. Predicting the unpredictable: drug‐induced QT prolongation and Torsades de Pointes. J Am Coll Cardiol. 2016;67:1639–50. PubMed

Kääb S, Crawford DC, Sinner MF, Behr ER, Kannankeril PJ, Wilde AA, et al. A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug‐induced torsades de pointes. Circ Cardiovasc Genet. 2012;5:91–9. PubMed PMC

Strauss DG, Vicente J, Johannesen L, Blinova K, Mason JW, Weeke P, et al. Common genetic variant risk score is associated with drug‐induced QT prolongation and Torsade de Pointes risk: a pilot study. Circulation. 2017;135:1300–10. PubMed PMC

Lahat H, Pras E, Eldar M. A missense mutation in CASQ2 is associated with autosomal recessive catecholamine‐induced polymorphic ventricular tachycardia in Bedouin families from Israel. Ann Med. 2004;36(Suppl 1):87–91. PubMed

Roux‐Buisson N, Cacheux M, Fourest‐Lieuvin A, Fauconnier J, Brocard J, Denjoy I, et al. Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human. Hum Mol Genet. 2012;21:2759–67. PubMed PMC

Devalla HD, Gélinas R, Aburawi EH, Beqqali A, Goyette P, Freund C, et al. TECRL, a new life‐threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT. EMBO Mol Med. 2016;8:1390–408. PubMed PMC

Webster G, Aburawi EH, Chaix MA, Chandler S, Foo R, Islam A, et al. Life‐threatening arrhythmias with autosomal recessive TECRL variants. Europace. 2021;23:781–8. PubMed PMC

Medeiros‐Domingo A, Bhuiyan ZA, Tester DJ, Hofman N, Bikker H, van Tintelen JP, 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. J Am Coll Cardiol. 2009;54:2065–74. PubMed PMC

Laurent G, Saal S, Amarouch MY, Béziau DM, Marsman RF, Faivre L, et al. Multifocal ectopic Purkinje‐related premature contractions: a new PubMed

Swan H, Amarouch MY, Leinonen J, Marjamaa A, Kucera JP, Laitinen‐Forsblom PJ, et al. Gain‐of‐function mutation of the PubMed

Tester DJ, Ackerman JP, Giudicessi JR, Ackerman NC, Cerrone M, Delmar M, et al. Plakophilin‐2 truncation variants in patients clinically diagnosed with catecholaminergic polymorphic ventricular tachycardia and decedents with exercise‐associated autopsy negative sudden unexplained death in the young. JACC Clin Electrophysiol. 2019;5:120–7. PubMed PMC

Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff J‐M, et al. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation. 2009;119:2426–34. PubMed

van der Werf C, Nederend I, Hofman N, van Geloven N, Ebink C, Frohn‐Mulder IM, et al. Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation‐carrying relatives. Circ Arrhythm Electrophysiol. 2012;5:748–56. PubMed

Giudicessi JR, Lieve KVV, Rohatgi RK, Koca F, Tester DJ, van der Werf C, et al. Assessment and validation of a phenotype‐enhanced variant classification framework to promote or demote RYR2 missense variants of uncertain significance. Circ Genom Precis Med. 2019;12:e002510. PubMed

Coumel P. Catecholaminergic‐induced severe ventricular arrhythmias with Adams‐Stokes syndrome in children: report of four cases. Br Heart J. 1978;40:28–37.

Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P. Catecholaminergic polymorphic ventricular tachycardia in children. A 7‐year follow‐up of 21 patients. Circulation. 1995;91:1512–9. PubMed

Tester DJ, Spoon DB, Valdivia HH, Makielski JC, Ackerman MJ. Targeted mutational analysis of the RyR2‐encoded cardiac ryanodine receptor in sudden unexplained death: a molecular autopsy of 49 medical examiner/coroner's cases. Mayo Clin Proc. 2004;79:1380–4. PubMed

Krahn AD, Healey JS, Simpson CS, Chauhan VS, Birnie DH, Champagne J, et al. Sentinel symptoms in patients with unexplained cardiac arrest: from the cardiac arrest survivors with preserved ejection fraction registry (CASPER). J Cardiovasc Electrophysiol. 2012;23:60–6. PubMed

Rucinski C, Winbo A, Marcondes L, Earle N, Stiles M, Stiles R, et al. A population‐based registry of patients with inherited cardiac conditions and resuscitated cardiac arrest. J Am Coll Cardiol. 2020;75:2698–707. PubMed

Leinonen JT, Crotti L, Djupsjöbacka A, Castelletti S, Junna N, Ghidoni A, et al. The genetics underlying idiopathic ventricular fibrillation: a special role for catecholaminergic polymorphic ventricular tachycardia? Int J Cardiol. 2018;250:139–45. PubMed

Tester DJ, Dura M, Carturan E, Reiken S, Wronska A, Marks AR, et al. A mechanism for sudden infant death syndrome (SIDS): stress‐induced leak via ryanodine receptors. Heart Rhythm. 2007;4:733–9. PubMed PMC

Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001;103:196–200. PubMed

Laitinen PJ, Brown KM, Piippo K, Swan H, Devaney JM, Brahmbhatt B, et al. Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation. 2001;103:485–90. PubMed

Sun B, Yao J, Ni M, Wei J, Zhong X, Guo W, et al. Cardiac ryanodine receptor calcium release deficiency syndrome. Sci Transl Med 2021;13:eaba7287. PubMed

Roston TM, Wei J, Guo W, Li Y, Zhong X, Wang R, et al. Clinical and functional characterization of ryanodine receptor 2 variants implicated in calcium‐release deficiency syndrome. JAMA Cardiol. 2022;7:84–92. PubMed PMC

Tester DJ, Arya P, Will M, Haglund CM, Farley AL, Makielski JC, et al. Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing. Heart Rhythm. 2006;3:800–5. PubMed

Kapplinger JD, Pundi KN, Larson NB, Callis TE, Tester DJ, Bikker H, et al. Yield of the RYR2 genetic test in suspected catecholaminergic polymorphic ventricular tachycardia and implications for test interpretation. Circ Genom Precis Med. 2018;11:e001424. PubMed PMC

Gray B, Bagnall RD, Lam L, Ingles J, Turner C, Haan E, et al. A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2016;13:1652–60. PubMed PMC

Ng K, Titus EW, Lieve KV, Roston TM, Mazzanti A, Deiter FH, et al. An international multicenter evaluation of inheritance patterns, arrhythmic risks, and underlying mechanisms of CASQ2‐catecholaminergic polymorphic ventricular tachycardia. Circulation. 2020;142:932–47. PubMed PMC

van der Werf C, Zwinderman AH, Wilde AA. Therapeutic approach for patients with catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments. Europace. 2012;14:175–83. PubMed

Kannankeril PJ, Moore JP, Cerrone M, Priori SG, Kertesz NJ, Ro PS, et al. Efficacy of flecainide in the treatment of catecholaminergic polymorphic ventricular tachycardia: a randomized clinical trial. JAMA Cardiol. 2017;2:759–66. PubMed PMC

De Ferrari GM, Dusi V, Spazzolini C, Bos JM, Abrams DJ, Berul CI, et al. Clinical management of catecholaminergic polymorphic ventricular tachycardia: the role of left cardiac sympathetic denervation. Circulation. 2015;131:2185–93. PubMed

van der Werf C, Lieve KV, Bos JM, Lane CM, Denjoy I, Roses‐Noguer F, et al. Implantable cardioverter‐defibrillators in previously undiagnosed patients with catecholaminergic polymorphic ventricular tachycardia resuscitated from sudden cardiac arrest. Eur Heart J. 2019;40:2953–61. PubMed

Yang Y, Hu D, Sacher F, Kusano KF, Li X, Barajas‐Martinez H, et al. Meta‐analysis of risk stratification of PubMed PMC

Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, et al. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls. Genet Med. 2021;23:47–58. PubMed PMC

Postema PG. About Brugada syndrome and its prevalence. Europace. 2012;14:925–8. PubMed

Milman A, Andorin A, Gourraud JB, Postema PG, Sacher F, Mabo P, et al. Profile of patients with Brugada syndrome presenting with their first documented arrhythmic event: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS). Heart Rhythm. 2018;15:716–24. PubMed

Kim YG, Oh SK, Choi HY, Choi JI. Inherited arrhythmia syndrome predisposing to sudden cardiac death. Korean J Intern Med. 2021;36:527–38. PubMed PMC

Papadakis M, Papatheodorou E, Mellor G, Raju H, Bastiaenen R, Wijeyeratne Y, et al. The diagnostic yield of Brugada syndrome after sudden death with normal autopsy. J Am Coll Cardiol. 2018;71:1204–14. PubMed

Tadros R, Nannenberg EA, Lieve KV, Skoric‐Milosavljevic D, Lahrouchi N, Lekanne Deprez RH, et al. Yield and pitfalls of ajmaline testing in the evaluation of unexplained cardiac arrest and sudden unexplained death: single‐center experience with 482 families. JACC Clin Electrophysiol. 2017;3:1400–8. PubMed

Shimizu W, Matsuo K, Takagi M, Tanabe Y, Aiba T, Taguchi A, et al. Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty‐seven‐lead body surface potential mapping and its application to twelve‐lead electrocardiograms. J Cardiovasc Electrophysiol. 2000;11:396–404. PubMed

Viskin S, Rosso R, Friedensohn L, Havakuk O, Wilde AA. Everybody has Brugada syndrome until proven otherwise? Heart Rhythm. 2015;12:1595–8. PubMed

Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, et al. J‐Wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge. Europace. 2017;19:665–94. PubMed PMC

Baranchuk A, Nguyen T, Ryu MH, Femenia F, Zareba W, Wilde AA, et al. Brugada phenocopy: new terminology and proposed classification. Ann Noninvasive Electrocardiol. 2012;17:299–314. PubMed PMC

Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, et al. Long‐term prognosis of patients diagnosed with Brugada syndrome: results from the FINGER Brugada Syndrome Registry. Circulation. 2010;121:635–43. PubMed

Lahrouchi N, Talajic M, Tadros R. Risk of arrhythmic events in drug‐induced Brugada syndrome. Heart Rhythm. 2017;14:1434–5. PubMed

Postema PG, Wolpert C, Amin AS, Probst V, Borggrefe M, Roden DM, et al. Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up‐to‐date website (www.brugadadrugs.org). Heart Rhythm. 2009;6:1335–41. PubMed PMC

Probst V, Wilde AA, Barc J, Sacher F, Babuty D, Mabo P, et al. PubMed

Peltenburg PJ, Blom NA, Vink AS, Kammeraad JAE, Breur H, Rammeloo LAJ, et al. In children and adolescents from Brugada syndrome‐families, only PubMed

Bezzina C, Veldkamp MW, van Den Berg MP, Postma AV, Rook MB, Viersma JW, et al. A single Na(+) channel mutation causing both long‐QT and Brugada syndromes. Circ Res. 1999;85:1206–13. PubMed

Sacilotto L, Scanavacca MI, Olivetti N, Lemes C, Pessente GD, Wulkan F, et al. Low rate of life‐threatening events and limitations in predicting invasive and noninvasive markers of symptoms in a cohort of type 1 Brugada syndrome patients: data and insights from the GenBra registry. J Cardiovasc Electrophysiol. 2020;31:2920–8. PubMed

Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, et al. Genotype‐phenotype correlation of PubMed

Ciconte G, Monasky MM, Santinelli V, Micaglio E, Vicedomini G, Anastasia L, et al. Brugada syndrome genetics is associated with phenotype severity. Eur Heart J. 2021;42:1082–90. PubMed PMC

Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. Circulation. 2019;140:e333–81. PubMed

Surawicz B, Childers R, Deal BJ, Gettes LS, Bailey JJ, Gorgels A, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009;53:976–81. PubMed

Asatryan B, Medeiros‐Domingo A. Molecular and genetic insights into progressive cardiac conduction disease. Europace. 2019;21:1145–58. PubMed

Neu A, Eiselt M, Paul M, Sauter K, Stallmeyer B, Isbrandt D, et al. A homozygous PubMed

Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, et al. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene ( PubMed PMC

Kyndt F, Probst V, Potet F, Demolombe S, Chevallier JC, Baro I, et al. Novel PubMed

Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction‐system disease. N Engl J Med. 1999;341:1715–24. PubMed

Birnie DH, Sauer WH, Bogun F, Cooper JM, Culver DA, Duvernoy CS, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm. 2014;11:1305–23. PubMed

Akhtar M, Elliott PM. Risk stratification for sudden cardiac death in non‐ischaemic dilated cardiomyopathy. Curr Cardiol Rep. 2019;21:155. PubMed PMC

Wahbi K, Ben Yaou R, Gandjbakhch E, Anselme F, Gossios T, Lakdawala NK, et al. Development and validation of a new risk prediction score for life‐threatening ventricular tachyarrhythmias in laminopathies. Circulation. 2019;140:293–302. PubMed

Van Rijsingen IAW, Arbustini E, Elliott PM, Mogensen J, Hermans‐Van Ast JF, Van Der Kooi AJ, et al. Risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers a European cohort study. J Am Coll Cardiol. 2012;59:493–500. PubMed

Nakajima K, Aiba T, Makiyama T, Nishiuchi S, Ohno S, Kato K, et al. Clinical manifestations and long‐term mortality in lamin A/C mutation carriers from a Japanese Multicenter Registry. Circ J. 2018;82:2707–14. PubMed

Tan RB, Gando I, Bu L, Cecchin F, Coetzee W. A homozygous PubMed

Makita N, Sasaki K, Groenewegen WA, Yokota T, Yokoshiki H, Murakami T, et al. Congenital atrial standstill associated with coinheritance of a novel PubMed

Kruse M, Schulze‐Bahr E, Corfield V, Beckmann A, Stallmeyer B, Kurtbay G, et al. Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. J Clin Invest. 2009;119:2737–44. PubMed PMC

Daumy X, Amarouch MY, Lindenbaum P, Bonnaud S, Charpentier E, Bianchi B, et al. Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I. Int J Cardiol. 2016;207:349–58. PubMed

Kamdar F, Garry DJ. Dystrophin‐deficient cardiomyopathy. J Am Coll Cardiol. 2016;67:2533–46. PubMed

Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992;69:385. PubMed

Bonne G, Quijano‐Roy S. Emery‐Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies. Handb Clin Neurol. 2013;113:1367–76. PubMed

Ishikawa T, Mishima H, Barc J, Takahashi MP, Hirono K, Terada S, et al. Cardiac emerinopathy: a nonsyndromic nuclear envelopathy with increased risk of thromboembolic stroke due to progressive atrial standstill and left ventricular noncompaction. Circ Arrhythm Electrophysiol. 2020;13:e008712. PubMed

Cenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C. Review: Danon disease: review of natural history and recent advances. Neuropathol Appl Neurobiol. 2020;46:303–22. PubMed

Arbustini E, Di Toro A, Giuliani L, Favalli V, Narula N, Grasso M. Cardiac phenotypes in hereditary muscle disorders: JACC state‐of‐the‐art review. J Am Coll Cardiol. 2018;72:2485–506. PubMed

Hu D, Hu D, Liu L, Barr D, Liu Y, Balderrabano‐Saucedo N, et al. Identification, clinical manifestation and structural mechanisms of mutations in AMPK associated cardiac glycogen storage disease. EBioMedicine. 2020;54:102723. PubMed PMC

Theis JL, Zimmermann MT, Larsen BT, Rybakova IN, Long PA, Evans JM, et al. TNNI3K mutation in familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy. Hum Mol Genet. 2014;23:5793–804. PubMed PMC

Seki A, Ishikawa T, Daumy X, Mishima H, Barc J, Sasaki R, et al. Progressive atrial conduction defects associated with bone malformation caused by a connexin‐45 mutation. J Am Coll Cardiol. 2017;70:358–70. PubMed

Limongelli G, Masarone D, Pacileo G. Mitochondrial disease and the heart. Heart. 2017;103:390–8. PubMed

Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res. 2005;96:800–7. PubMed

Templin C, Ghadri JR, Rougier JS, Baumer A, Kaplan V, Albesa M, et al. Identification of a novel loss‐of‐function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J. 2011;32:1077–88. PubMed PMC

Gollob MH, Redpath CJ, Roberts JD. The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol. 2011;57:802–12. PubMed

Giustetto C, Scrocco C, Schimpf R, Maury P, Mazzanti A, Levetto M, et al. Usefulness of exercise test in the diagnosis of short QT syndrome. Europace. 2015;17:628–34. PubMed

Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M, et al. Sudden death associated with short‐QT syndrome linked to mutations in HERG. Circulation. 2004;109:30–5. PubMed

Bellocq C, van Ginneken AC, Bezzina CR, Alders M, Escande D, Mannens MM, et al. Mutation in the KCNQ1 gene leading to the short QT‐interval syndrome. Circulation. 2004;109:2394–7. PubMed

Thorsen K, Dam VS, Kjaer‐Sorensen K, Pedersen LN, Skeberdis VA, Jurevicius J, et al. Loss‐of‐activity‐mutation in the cardiac chloride‐bicarbonate exchanger AE3 causes short QT syndrome. Nat Commun. 2017;8:1696. PubMed PMC

Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, 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. Circulation. 2007;115:442–9. PubMed PMC

Hancox JC, Whittaker DG, Du C, Stuart AG, Zhang H. Emerging therapeutic targets in the short QT syndrome. Expert Opin Ther Targets. 2018;22:439–51. PubMed

Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion‐dependent carnitine transporter. Nat Genet. 1999;21:91–4. PubMed

Roussel J, Labarthe F, Thireau J, Ferro F, Farah C, Roy J, et al. Carnitine deficiency induces a short QT syndrome. Heart Rhythm. 2016;13:165–74. PubMed

Gélinas R, Leach E, Horvath G, Laksman Z. Molecular autopsy implicates primary carnitine deficiency in sudden unexplained death and reversible short QT syndrome. Can J Cardiol 2019;35:1256.e1–2. PubMed

Giustetto C, Schimpf R, Mazzanti A, Scrocco C, Maury P, Anttonen O, et al. Long‐term follow‐up of patients with short QT syndrome. J Am Coll Cardiol. 2011;58:587–95. PubMed

Hu D, Li Y, Zhang J, Pfeiffer R, Gollob MH, Healey J, et al. The phenotypic spectrum of a mutation hotspot responsible for the short QT syndrome. JACC Clin Electrophysiol. 2017;3:727–43. PubMed

Mazzanti A, Maragna R, Vacanti G, Kostopoulou A, Marino M, Monteforte N, et al. Hydroquinidine prevents life‐threatening arrhythmic events in patients with short QT syndrome. J Am Coll Cardiol. 2017;70:3010–5. PubMed

Raschwitz LS, El‐Battrawy I, Schlentrich K, Besler J, Veith M, Roterberg G, et al. Differences in short QT syndrome subtypes: a systematic literature review and pooled analysis. Front Genet. 2019;10:1312. PubMed PMC

Harrell DT, Ashihara T, Ishikawa T, Tominaga I, Mazzanti A, Takahashi K, et al. Genotype‐dependent differences in age of manifestation and arrhythmia complications in short QT syndrome. Int J Cardiol. 2015;190:393–402. PubMed

Morita H, Kusano‐Fukushima K, Nagase S, Fujimoto Y, Hisamatsu K, Fujio H, et al. Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. J Am Coll Cardiol. 2002;40:1437–44. PubMed

Olson TM, Michels VV, Ballew JD, Reyna SP, Karst ML, Herron KJ, et al. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA. 2005;293:447–54. PubMed PMC

McNair WP, Ku L, Taylor MR, Fain PR, Dao D, Wolfel E, et al. PubMed

Li Q, Huang H, Liu G, Lam K, Rutberg J, Green MS, et al. Gain‐of‐function mutation of Nav1.5 in atrial fibrillation enhances cellular excitability and lowers the threshold for action potential firing. Biochem Biophys Res Commun. 2009;380:132–7. PubMed

Chen YH, Xu SJ, Bendahhou S, Wang XL, Wang Y, Xu WY, et al. KCNQ1 gain‐of‐function mutation in familial atrial fibrillation. Science. 2003;299:251–4. PubMed

Orr N, Arnaout R, Gula LJ, Spears DA, Leong‐Sit P, Li Q, et al. A mutation in the atrial‐specific myosin light chain gene (MYL4) causes familial atrial fibrillation. Nat Commun. 2016;7:11303. PubMed PMC

Kumar S, Baldinger SH, Gandjbakhch E, Maury P, Sellal JM, Androulakis AF, et al. Long‐term arrhythmic and nonarrhythmic outcomes of lamin A/C mutation carriers. J Am Coll Cardiol. 2016;68:2299–307. PubMed

Choi SH, Weng LC, Roselli C, Lin H, Haggerty CM, Shoemaker MB et al; For the DiscovEHR study and the NHLBI Trans‐Omics for Precision Medicine (TOPMed) Consortium. Association between titin loss‐of‐function variants and early‐onset atrial fibrillation. JAMA 2018;320:2354–64. PubMed PMC

Yoneda ZT, Anderson KC, Quintana JA, O'Neill MJ, Sims RA, Glazer AM, et al. Early‐onset atrial fibrillation and the prevalence of rare variants in cardiomyopathy and arrhythmia genes. JAMA Cardiol. 2021;6:1371–9. PubMed PMC

Goodyer WR, Dunn K, Caleshu C, Jackson M, Wylie J, Moscarello T, et al. Broad genetic testing in a clinical setting uncovers a high prevalence of titin loss‐of‐function variants in very early onset atrial fibrillation. Circ Genom Precis Med. 2019;12:e002713. PubMed PMC

Roberts R. Mechanisms of disease: genetic mechanisms of atrial fibrillation. Nat Clin Pract Cardiovasc Med. 2006;3:276–82. PubMed

Darbar D, Herron KJ, Ballew JD, Jahangir A, Gersh BJ, Shen WK, et al. Familial atrial fibrillation is a genetically heterogeneous disorder. J Am Coll Cardiol. 2003;41:2185–92. PubMed

Sébillon P, Bouchier C, Bidot LD, Bonne G, Ahamed K, Charron P, et al. Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations. J Med Genet. 2003;40:560–7. PubMed PMC

Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH, et al. Ankyrin‐B mutation causes type 4 long‐QT cardiac arrhythmia and sudden cardiac death. Nature. 2003;421:634–9. PubMed

Hong K, Piper DR, Diaz‐Valdecantos A, Brugada J, Oliva A, Burashnikov E, et al. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc Res. 2005;68:433–40. PubMed

Bhuiyan ZA, van den Berg MP, van Tintelen JP, Bink‐Boelkens MT, Wiesfeld AC, Alders M, et al. Expanding spectrum of human RYR2‐related disease: new electrocardiographic, structural, and genetic features. Circulation. 2007;116:1569–76. PubMed

Sy RW, Gollob MH, Klein GJ, Yee R, Skanes AC, Gula LJ, et al. Arrhythmia characterization and long‐term outcomes in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2011;8:864–71. PubMed

Gillmore JD, Booth DR, Pepys MB, Hawkins PN. Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man. Heart. 1999;82:e2. PubMed PMC

Gutierrez‐Roelens I, De Roy L, Ovaert C, Sluysmans T, Devriendt K, Brunner HG, et al. A novel CSX/NKX2‐5 mutation causes autosomal‐dominant AV block: are atrial fibrillation and syncopes part of the phenotype? Eur J Hum Genet. 2006;14:1313–6. PubMed

Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, et al. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation. 2001;104:3030–3. PubMed

Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011;57:e101–98. PubMed

Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, et al. Kv1.5 channelopathy due to KCNA5 loss‐of‐function mutation causes human atrial fibrillation. Hum Mol Genet. 2006;15:2185–91. PubMed

Deo M, Ruan Y, Pandit SV, Shah K, Berenfeld O, Blaufox A, et al. KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proc Natl Acad Sci USA. 2013;110:4291–6. PubMed PMC

Hong K, Bjerregaard P, Gussak I, Brugada R. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J Cardiovasc Electrophysiol. 2005;16:394–6. PubMed

Li RG, Xu YJ, Ye WG, Li YJ, Chen H, Qiu XB, et al. Connexin45 (GJC1) loss‐of‐function mutation contributes to familial atrial fibrillation and conduction disease. Heart Rhythm. 2021;18:684–93. PubMed

Hodgson‐Zingman DM, Karst ML, Zingman LV, Heublein DM, Darbar D, Herron KJ, et al. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med. 2008;359:158–65. PubMed PMC

Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with Bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;140:e382–482. PubMed

Jensen MT, Wod M, Galatius S, Hjelmborg JB, Jensen GB, Christensen K. Heritability of resting heart rate and association with mortality in middle‐aged and elderly twins. Heart. 2018;104:30–6. PubMed PMC

Holm H, Gudbjartsson DF, Arnar DO, Thorleifsson G, Thorgeirsson G, Stefansdottir H, et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet. 2010;42:117–22. PubMed

Holm H, Gudbjartsson DF, Sulem P, Masson G, Helgadottir HT, Zanon C, et al. A rare variant in MYH6 is associated with high risk of sick sinus syndrome. Nat Genet. 2011;43:316–20. PubMed PMC

Ramirez J, Duijvenboden SV, Ntalla I, Mifsud B, Warren HR, Tzanis E, et al. Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system. Nat Commun. 2018;9:1947. PubMed PMC

Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, et al. 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with Bradycardia and cardiac conduction delay: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol. 2019;74:932–87. PubMed

Veldkamp MW, Wilders R, Baartscheer A, Zegers JG, Bezzina CR, Wilde AA. Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res. 2003;92:976–83. PubMed

Chiang DY, Kim JJ, Valdes SO, de la Uz C, Fan Y, Orcutt J, et al. Loss‐of‐function PubMed PMC

Schulze‐Bahr E, Neu A, Friederich P, Kaupp UB, Breithardt G, Pongs O, et al. Pacemaker channel dysfunction in a patient with sinus node disease. J Clin Invest. 2003;111:1537–45. PubMed PMC

Milano A, Vermeer AM, Lodder EM, Barc J, Verkerk AO, Postma AV, et al. HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. J Am Coll Cardiol. 2014;64:745–56. PubMed

Stallmeyer B, Kuß J, Kotthoff S, Zumhagen S, Vowinkel K, Rinné S, et al. A mutation in the G‐protein gene GNB2 causes familial sinus node and atrioventricular conduction dysfunction. Circ Res. 2017;120:e33–44. PubMed

Righi D, Silvetti MS, Drago F. Sinus bradycardia, junctional rhythm, and low‐rate atrial fibrillation in Short QT syndrome during 20 years of follow‐up: three faces of the same genetic problem. Cardiol Young. 2016;26:589–92. PubMed

Whittaker DG, Colman MA, Ni H, Hancox JC, Zhang H. Human atrial arrhythmogenesis and sinus bradycardia in KCNQ1‐linked short QT syndrome: insights from computational modelling. Front Physiol. 2018;9:1402. PubMed PMC

Kuß J, Stallmeyer B, Goldstein M, Rinné S, Pees C, Zumhagen S, et al. Familial sinus node disease caused by a gain of GIRK (G‐protein activated inwardly rectifying K(+) channel) channel function. Circ Genom Precis Med. 2019;12:e002238. PubMed

Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, et al. Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation. Circulation. 2019;139:2157–69. PubMed

Arbel‐Ganon L, Behar JA, Gomez AM, Yaniv Y. Distinct mechanisms mediate pacemaker dysfunction associated with catecholaminergic polymorphic ventricular tachycardia mutations: insights from computational modeling. J Mol Cell Cardiol. 2020;143:85–95. PubMed

Baig SM, Koschak A, Lieb A, Gebhart M, Dafinger C, Nurnberg G, et al. Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. Nat Neurosci. 2011;14:77–84. PubMed

Liaqat K, Schrauwen I, Raza SI, Lee K, Hussain S, Chakchouk I et al; University of Washington Center for Mendelian Genomics. Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance. J Hum Genet 2019;64:153–60. PubMed PMC

Lodder EM, De Nittis P, Koopman CD, Wiszniewski W, Moura de Souza CF, Lahrouchi N, et al. GNB5 mutations cause an autosomal‐recessive multisystem syndrome with sinus bradycardia and cognitive disability. Am J Hum Genet 2016;99:786. PubMed PMC

Chetaille P, Preuss C, Burkhard S, Cote JM, Houde C, Castilloux J, et al. Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nat Genet. 2014;46:1245–9. PubMed

Kong D, Zhan Y, Liu C, Hu Y, Zhou Y, Luo J, et al. A novel mutation of the EMD gene in a family with cardiac conduction abnormalities and a high incidence of sudden cardiac death. Pharmgenomics Pers Med. 2019;12:319–27. PubMed PMC

Wasserburger RH, Alt WJ. The normal RS‐T segment elevation variant. Am J Cardiol. 1961;8:184–92. PubMed

Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA, et al. Long‐term outcome associated with early repolarization on electrocardiography. N Engl J Med. 2009;361:2529–37. PubMed

Rosso R, Kogan E, Belhassen B, Rozovski U, Scheinman MM, Zeltser D, et al. J‐point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol. 2008;52:1231–8. PubMed

Haïssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358:2016–23. PubMed

Aizawa Y, Chinushi M, Hasegawa K, Naiki N, Horie M, Kaneko Y, et al. Electrical storm in idiopathic ventricular fibrillation is associated with early repolarization. J Am Coll Cardiol. 2013;62:1015–9. PubMed

Nam GB, Kim YH, Antzelevitch C. Augmentation of J waves and electrical storms in patients with early repolarization. N Engl J Med. 2008;358:2078–9. PubMed PMC

Koncz I, Gurabi Z, Patocskai B, Panama BK, Szél T, Hu D, et al. Mechanisms underlying the development of the electrocardiographic and arrhythmic manifestations of early repolarization syndrome. J Mol Cell Cardiol. 2014;68:20–8. PubMed PMC

Ghosh S, Cooper DH, Vijayakumar R, Zhang J, Pollak S, Haïssaguerre M, et al. Early repolarization associated with sudden death: insights from noninvasive electrocardiographic imaging. Heart Rhythm. 2010;7:534–7. PubMed PMC

Nademanee K, Haissaguerre M, Hocini M, Nogami A, Cheniti G, Duchateau J, et al. Mapping and ablation of ventricular fibrillation associated with early repolarization syndrome. Circulation. 2019;140:1477–90. PubMed

Haïssaguerre M, Nademanee K, Hocini M, Cheniti G, Duchateau J, Frontera A, et al. Depolarization versus repolarization abnormality underlying inferolateral J‐wave syndromes: new concepts in sudden cardiac death with apparently normal hearts. Heart Rhythm. 2019;16:781–90. PubMed PMC

Boukens BJ, Benjacholamas V, van Amersfoort S, Meijborg VM, Schumacher C, Jensen B, et al. Structurally abnormal myocardium underlies ventricular fibrillation storms in a patient diagnosed with the early repolarization pattern. JACC Clin Electrophysiol. 2020;6:1395–404. PubMed

Reinhard W, Kaess BM, Debiec R, Nelson CP, Stark K, Tobin MD, et al. Heritability of early repolarization: a population‐based study. Circ Cardiovasc Genet. 2011;4:134–8. PubMed

Bastiaenen R, Nolte IM, Munroe PB, Riese H, Nelson C, O'Connor H, et al. The narrow‐sense and common single nucleotide polymorphism heritability of early repolarization. Int J Cardiol. 2019;279:135–40. PubMed

Honarbakhsh S, Srinivasan N, Kirkby C, Firman E, Tobin L, Finlay M, et al. Medium‐term outcomes of idiopathic ventricular fibrillation survivors and family screening: a multicentre experience. Europace. 2017;19:1874–80. PubMed

Nunn LM, Bhar‐Amato J, Lowe MD, Macfarlane PW, Rogers P, McKenna WJ, et al. Prevalence of J‐point elevation in sudden arrhythmic death syndrome families. J Am Coll Cardiol. 2011;58:286–90. PubMed

Mellor G, Nelson CP, Robb C, Raju H, Wijeyeratne Y, Hengstenberg C, et al. The prevalence and significance of the early repolarization pattern in sudden arrhythmic death syndrome families. Circ Arrhythm Electrophysiol. 2016;9:e003960. PubMed

Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, et al. Electrocardiographic characteristics and PubMed

Giudicessi JR, Ye D, Stutzman MJ, Zhou W, Tester DJ, Ackerman MJ. Prevalence and electrophysiological phenotype of rare PubMed

Zhang ZH, Barajas‐Martínez H, Xia H, Li B, Capra JA, Clatot J, et al. Distinct features of probands with early repolarization and brugada syndromes carrying PubMed PMC

Chauveau S, Janin A, Till M, Morel E, Chevalier P, Millat G. Early repolarization syndrome caused by de novo duplication of KCND3 detected by next‐generation sequencing. HeartRhythm Case Rep. 2017;3:574–8. PubMed PMC

Takayama K, Ohno S, Ding WG, Ashihara T, Fukumoto D, Wada Y, et al. A de novo gain‐of‐function KCND3 mutation in early repolarization syndrome. Heart Rhythm. 2019;16:1698–706. PubMed

Teumer A, Trenkwalder T, Kessler T, Jamshidi Y, van den Berg ME, Kaess B, et al. KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern. JCI Insight. 2019;4:e131156. PubMed PMC

Barajas‐Martínez H, Hu D, Ferrer T, Onetti CG, Wu Y, Burashnikov E, et al. Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. Heart Rhythm. 2012;9:548–55. PubMed PMC

Medeiros‐Domingo A, Tan BH, Crotti L, Tester DJ, Eckhardt L, Cuoretti A, 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. Heart Rhythm. 2010;7:1466–71. PubMed PMC

Vidaillet HJ Jr, Pressley JC, Henke E, Harrell FE Jr, German LD. Familial occurrence of accessory atrioventricular pathways (preexcitation syndrome). N Engl J Med. 1987;317:65–9. PubMed

Deal BJ, Keane JF, Gillette PC, Garson A Jr. Wolff‐Parkinson‐White syndrome and supraventricular tachycardia during infancy: management and follow‐up. J Am Coll Cardiol. 1985;5:130–5. PubMed

MacRae CA, Ghaisas N, Kass S, Donnelly S, Basson CT, Watkins HC, et al. Familial hypertrophic cardiomyopathy with Wolff‐Parkinson‐White syndrome maps to a locus on chromosome 7q3. J Clin Invest. 1995;96:1216–20. PubMed PMC

Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, et al. Identification of a gene responsible for familial Wolff‐Parkinson‐White syndrome. N Engl J Med. 2001;344:1823–31. PubMed

Lopez‐Sainz A, Dominguez F, Lopes LR, Ochoa JP, Barriales‐Villa R, Climent V, et al. Clinical features and natural history of PRKAG2 variant cardiac glycogenosis. J Am Coll Cardiol. 2020;76:186–97. PubMed

Landstrom AP, Parvatiyar MS, Pinto JR, Marquardt ML, Bos JM, Tester DJ, et al. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1‐encoded troponin C. J Mol Cell Cardiol. 2008;45:281–8. PubMed PMC

Geier C, Gehmlich K, Ehler E, Hassfeld S, Perrot A, Hayess K, et al. Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet. 2008;17:2753–65. PubMed

Landstrom AP, Weisleder N, Batalden KB, Bos JM, Tester DJ, Ommen SR, et al. Mutations in JPH2‐encoded junctophilin‐2 associated with hypertrophic cardiomyopathy in humans. J Mol Cell Cardiol. 2007;42:1026–35. PubMed PMC

Al Senaidi K, Joshi N, Al‐Nabhani M, Al‐Kasbi G, Al Farqani A, Al‐Thihli K, et al. Phenotypic spectrum of ALPK3‐related cardiomyopathy. Am J Med Genet A. 2019;179:1235–40. PubMed

Ochoa JP, Sabater‐Molina M, García‐Pinilla JM, Mogensen J, Restrepo‐Córdoba A, Palomino‐Doza J, et al. Formin homology 2 domain containing 3 (FHOD3) is a genetic basis for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2018;72:2457–67. PubMed

Alfares AA, Kelly MA, Mcdermott G, Funke BH, Lebo MS, Baxter SB, et al. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015;17:880–8. PubMed

Ingles J, Sarina T, Yeates L, Hunt L, Macciocca I, McCormack L, et al. Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy. Genet Med. 2013;15:972–7. PubMed

van Velzen HG, Schinkel AFL, Baart SJ, Oldenburg RA, Frohn‐Mulder IME, van Slegtenhorst MA, et al. Outcomes of contemporary family screening in hypertrophic cardiomyopathy. Circ Genom Precis Med. 2018;11:e001896. PubMed

Norrish G, Jager J, Field E, Quinn E, Fell H, Lord E, et al. Yield of clinical screening for hypertrophic cardiomyopathy in child first‐degree relatives. Circulation. 2019;140:184–92. PubMed PMC

Pena JLB, Santos WC, Siqueira MHA, Sampaio IH, Moura ICG, Sternick EB. Glycogen storage cardiomyopathy (PRKAG2): diagnostic findings of standard and advanced echocardiography techniques. Eur Heart J Cardiovasc Imaging. 2021;22:800–7. PubMed

Maron BJ, Roberts WC, Arad M, Haas TS, Spirito P, Wright GB, et al. Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy. JAMA. 2009;301:1253–9. PubMed PMC

Elliott P, Baker R, Pasquale F, Quarta G, Ebrahim H, Mehta AB et al; ACES study group. Prevalence of Anderson‐Fabry disease in patients with hypertrophic cardiomyopathy: the European Anderson‐Fabry Disease survey. Heart 2011;97:1957–60. PubMed

Benson MD, Waddington‐Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med. 2018;379:22–31. PubMed

Yavari A, Bellahcene M, Bucchi A, Sirenko S, Pinter K, Herring N, et al. Mammalian γ2 AMPK regulates intrinsic heart rate. Nat Commun. 2017;8:1258. PubMed PMC

Sternick EB, Oliva A, Gerken LM, Magalhães L, Scarpelli R, Correia FS, et al. Clinical, electrocardiographic, and electrophysiologic characteristics of patients with a fasciculoventricular pathway: the role of PRKAG2 mutation. Heart Rhythm. 2011;8:58–64. PubMed

Das KJ, Ingles J, Bagnall RD, Semsarian C. Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment. Genet Med. 2014;16:286–93. PubMed

Ahmad F, McNally EM, Ackerman MJ, Baty LC, Day SM, Kullo IJ, et al. Establishment of specialized clinical cardiovascular genetics programs: recognizing the need and meeting standards: a scientific statement from the American Heart Association. Circ Genom Precis Med. 2019;12:e000054. PubMed

Ranthe MF, Carstensen L, Øyen N, Jensen MK, Axelsson A, Wohlfahrt J, et al. Risk of cardiomyopathy in younger persons with a family history of death from cardiomyopathy: a nationwide family study in a cohort of 3.9 million persons. Circulation. 2015;132:1013–9. PubMed

Bagnall RD, Ingles J, Dinger ME, Cowley MJ, Ross SB, Minoche AE, et al. Whole genome sequencing improves outcomes of genetic testing in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2018;72:419–29. PubMed

Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D et al; For the SHaRe Investigators. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation 2018;138:1387–98. PubMed PMC

Thomson KL, Ormondroyd E, Harper AR, Dent T, McGuire K, Baksi J. et al; NIHR BioResource – Rare Diseases Consortium. Analysis of 51 proposed hypertrophic cardiomyopathy genes from genome sequencing data in sarcomere negative cases has negligible diagnostic yield. Genet Med. 2019;21:1576–84. PubMed PMC

Valdés‐Mas R, Gutiérrez‐Fernández A, Gómez J, Coto E, Astudillo A, Puente DA, et al. Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy. Nat Commun. 2014;5:5326. PubMed

Ingles J, Burns C, Bagnall RD, Lam L, Yeates L, Sarina T, et al. Nonfamilial hypertrophic cardiomyopathy: prevalence, natural history, and clinical implications. Circ Cardiovasc Genet. 2017;10:e001620. PubMed

van Capelle CI, Poelman E, Frohn‐Mulder IM, Koopman LP, van den Hout JMP, Régal L, et al. Cardiac outcome in classic infantile Pompe disease after 13 years of treatment with recombinant human acid alpha‐glucosidase. Int J Cardiol. 2018;269:104–10. PubMed

Landstrom AP, Adekola BA, Bos JM, Ommen SR, Ackerman MJ. PLN‐encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing. Am Heart J. 2011;161:165–71. PubMed PMC

Kouz K, Lissewski C, Spranger S, Mitter D, Riess A, Lopez‐Gonzalez V, et al. Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation. Genet Med. 2016;18:1226–34. PubMed

Mathew J, Zahavich L, Lafreniere‐Roula M, Wilson J, George K, Benson L, et al. Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy. Clin Genet. 2018;93:310–9. PubMed

Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J Med Genet. 2005;42:e59. PubMed PMC

Miron A, Lafreniere‐Roula MS, Fan CP, Armstrong KR, Dragulescu A, Papaz T, et al. A validated model for sudden cardiac death risk prediction in pediatric hypertrophic cardiomyopathy. Circulation. 2020;142:217–29. PubMed PMC

Christiaans I, Birnie E, Bonsel GJ, Mannens MM, Michels M, Majoor‐Krakauer D, et al. Manifest disease, risk factors for sudden cardiac death, and cardiac events in a large nationwide cohort of predictively tested hypertrophic cardiomyopathy mutation carriers: determining the best cardiological screening strategy. Eur Heart J. 2011;32:1161–70. PubMed

Haas J, Frese KS, Peil B, Kloos W, Keller A, Nietsch R, et al. Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J 2015;36:1123–35a. PubMed

Ware JS, Amor‐Salamanca A, Tayal U, Govind R, Serrano I, Salazar‐Mendiguchía J, et al. Genetic etiology for alcohol‐induced cardiac toxicity. J Am Coll Cardiol. 2018;71:2293–302. PubMed PMC

Ware JS, Li J, Mazaika E, Yasso CM, Desouza T, Cappola TP. et al; IMAC‐2 and IPAC Investigators. Shared genetic predisposition in peripartum and dilated cardiomyopathies. N Engl J Med. 2016;374:233–41. PubMed PMC

Thuillot M, Maupain C, Gandjbakhch E, Waintraub X, Hidden‐Lucet F, Isnard R, et al. External validation of risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers. Eur J Heart Fail. 2019;21:253–4. PubMed

Peters S, Kumar S, Elliott P, Kalman JM, Fatkin D. Arrhythmic genotypes in familial dilated cardiomyopathy: implications for genetic testing and clinical management. Heart Lung Circ. 2019;28:31–8. PubMed

Kayvanpour E, Sedaghat‐Hamedani F, Amr A, Lai A, Haas J, Holzer DB, et al. Genotype‐phenotype associations in dilated cardiomyopathy: meta‐analysis on more than 8000 individuals. Clin Res Cardiol. 2017;106:127–39. PubMed

Ortiz‐Genga MF, Cuenca S, Dal Ferro M, Zorio E, Salgado‐Aranda R, Climent V, et al. Truncating FLNC mutations are associated with high‐risk dilated and arrhythmogenic cardiomyopathies. J Am Coll Cardiol. 2016;68:2440–51. PubMed

Ader F, De Groote P, Réant P, Rooryck‐Thambo C, Dupin‐Deguine D, Rambaud C, et al. FLNC pathogenic variants in patients with cardiomyopathies: prevalence and genotype‐phenotype correlations. Clin Genet. 2019;96:317–29. PubMed

Wahbi K, Béhin A, Charron P, Dunand M, Richard P, Meune C, et al. High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES gene mutations: a 10‐year longitudinal study. Neuromuscul Disord. 2012;22:211–8. PubMed

Heliö T, Elliott P, Koskenvuo JW, Gimeno JR, Tavazzi L, Tendera M, et al. ESC EORP Cardiomyopathy Registry: real‐life practice of genetic counselling and testing in adult cardiomyopathy patients. ESC Heart Fail. 2020;7:3013–21. PubMed PMC

European Society of Human Genetics . Genetic testing in asymptomatic minors: recommendations of the European Society of Human Genetics. Eur J Hum Genet. 2009;17:720–1. PubMed PMC

Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29:270–6. PubMed

Keren A, Gottlieb S, Tzivoni D, Stern S, Yarom R, Billingham ME, et al. Mildly dilated congestive cardiomyopathy. Use of prospective diagnostic criteria and description of the clinical course without heart transplantation. Circulation. 1990;81:506–17. PubMed

Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA. Frequency and phenotypes of familial dilated cardiomyopathy. J Am Coll Cardiol. 1998;31:186–94. PubMed

Mahon NG, Murphy RT, MacRae CA, Caforio AL, Elliott PM, McKenna WJ. Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease. Ann Intern Med. 2005;143:108–15. PubMed

Michels VV, Moll PP, Miller FA, Tajik AJ, Chu JS, Driscoll DJ, et al. The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992;326:77–82. PubMed

Asselbergs FW, Sammani A, Elliott P, Gimeno JR, Tavazzi L, Tendera M et al; Cardiomyopathy & Myocarditis Registry Investigators Group. Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry. ESC Heart Fail 2021;8:95–105. PubMed PMC

Garcia‐Pavia P, Kim Y, Restrepo‐Cordoba MA, Lunde IG, Wakimoto H, Smith AM, et al. Genetic variants associated with cancer therapy‐induced cardiomyopathy. Circulation. 2019;140:31–41. PubMed PMC

Kontorovich AR, Patel N, Moscati A, Richter F, Peter I, Purevjav E, et al. Myopathic cardiac genotypes increase risk for myocarditis. JACC Basic Transl Sci. 2021;6:584–92. PubMed PMC

Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, et al. Reevaluating the genetic contribution of monogenic dilated cardiomyopathy. Circulation. 2020;141:387–98. PubMed PMC

Jordan E, Hershberger RE. Considering complexity in the genetic evaluation of dilated cardiomyopathy. Heart. 2021;107:106–12. PubMed PMC

Garnier S, Harakalova M, Weiss S, Mokry M, Regitz‐Zagrosek V, Hengstenberg C, et al. Genome‐wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23.Eur Heart J 2021;42:2000–11. PubMed PMC

Mogensen J, van Tintelen JP, Fokstuen S, Elliott P, van Langen IM, Meder B, et al. The current role of next‐generation DNA sequencing in routine care of patients with hereditary cardiovascular conditions: a viewpoint paper of the European Society of Cardiology working group on myocardial and pericardial diseases and members of the European Society of Human Genetics. Eur Heart J. 2015;36:1367–70. PubMed

Peters S, Johnson R, Birch S, Zentner D, Hershberger RE, Fatkin D. Familial dilated cardiomyopathy. Heart Lung Circ. 2020;29:566–74. PubMed

Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non‐dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2016;37:1850–8. PubMed

Hasselberg NE, Haland TF, Saberniak J, Brekke PH, Berge KE, Leren TP, et al. Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation. Eur Heart J. 2018;39:853–60. PubMed PMC

Kuliev A, Pomerantseva E, Polling D, Verlinsky O, Rechitsky S. PGD for inherited cardiac diseases. Reprod Biomed Online. 2012;24:443–53. PubMed

Hoorntje ET, Bollen IA, Barge‐Schaapveld DQ, van Tienen FH, Te Meerman GJ, Jansweijer JA, et al. Lamin A/C‐related cardiac disease: late onset with a variable and mild phenotype in a large cohort of patients with the lamin A/C p.(Arg331Gln) founder mutation. Circ Cardiovasc Genet 2017;10:e001631. PubMed

Verdonschot JAJ, Hazebroek MR, Derks KWJ, Barandiarán Aizpurua A, Merken JJ, Wang P, et al. Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long‐term life‐threatening arrhythmias. Eur Heart J. 2018;39:864–73. PubMed

Gigli M, Merlo M, Graw SL, Barbati G, Rowland TJ, Slavov DB, et al. Genetic risk of arrhythmic phenotypes in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2019;74:1480–90. PubMed PMC

Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019;16:e301–72. PubMed

Van Lint FHM, Murray B, Tichnell C, Zwart R, Amat N, Lekanne Deprez RH, et al. Arrhythmogenic right ventricular cardiomyopathy‐associated desmosomal variants are rarely de novo. Circ Genom Precis Med. 2019;12:e002467. PubMed

Corrado D, Perazzolo Marra M, Zorzi A, Beffagna G, Cipriani A, Lazzari MD, et al. Diagnosis of arrhythmogenic cardiomyopathy: the Padua criteria. Int J Cardiol. 2020;319:106–14. PubMed

Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, 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). Heart Rhythm. 2011;8:1308–39. PubMed

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, et al. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2017;19:192–203. PubMed PMC

Corrado D, van Tintelen PJ, McKenna WJ, Hauer RNW, Anastastakis A, Asimaki A, et al. Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis. Eur Heart J. 2020;41:1414–29. PubMed PMC

Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, et al. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace. 2010;12:861–8. PubMed

van der Zwaag PA, van Rijsingen IA, Asimaki A, Jongbloed JD, van Veldhuisen DJ, Wiesfeld AC, et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur J Heart Fail. 2012;14:1199–207. PubMed PMC

Hodgkinson KA, Connors SP, Merner N, Haywood A, Young TL, McKenna WJ, et al. The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43. Clin Genet. 2013;83:321–31. PubMed

Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001;10:189–94. PubMed

Protonotarios A, Brodehl A, Asimaki A, Jager J, Quinn E, Stanasiuk C, et al. The novel desmin variant p.Leu115Ile is associated with a unique form of biventricular Arrhythmogenic Cardiomyopathy. Can J Cardiol. 2021;37:857–66. PubMed

Bermúdez‐Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, et al. Novel desmin mutation p.Glu401Asp impairs filament formation, disrupts cell membrane integrity, and causes severe arrhythmogenic left ventricular cardiomyopathy/dysplasia. Circulation. 2018;137:1595–610. PubMed

Marey I, Fressart V, Rambaud C, Fornes P, Martin L, Grotto S, et al. Clinical impact of post‐mortem genetic testing in cardiac death and cardiomyopathy. Open Med (Wars). 2020;15:435–46. PubMed PMC

Groeneweg JA, Bhonsale A, James CA, Te Riele AS, Dooijes D, Tichnell C, et al. Clinical presentation, long‐term follow‐up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members. Circ Cardiovasc Genet. 2015;8:437–46. PubMed

Quarta G, Muir A, Pantazis A, Syrris P, Gehmlich K, Garcia‐Pavia P, et al. Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria. Circulation. 2011;123:2701–9. PubMed

James CA, Syrris P, van Tintelen JP, Calkins H. The role of genetics in cardiovascular disease: arrhythmogenic cardiomyopathy. Eur Heart J. 2020;41:1393–400. PubMed

Ghidoni A, Elliott PM, Syrris P, Calkins H, James CA, Judge DP, et al. Cadherin 2‐related arrhythmogenic cardiomyopathy: prevalence and clinical features. Circ Genom Precis Med. 2021;14:e003097. PubMed PMC

Ross SB, Singer ES, Driscoll E, Nowak N, Yeates L, Puranik R, et al. Genetic architecture of left ventricular noncompaction in adults. Hum Genome Var. 2020;7:33. PubMed PMC

Verstraelen TE, van Lint FHM, Bosman LP, de Brouwer R, Proost VM, Abeln BGS, et al. Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers‐reaching the frontiers of individual risk prediction. Eur Heart J. 2021;42:2842–50. PubMed PMC

Cadrin‐Tourigny J, Bosman LP, Wang W, Tadros R, Bhonsale A, Bourfiss M, et al. Sudden cardiac death prediction in arrhythmogenic right ventricular cardiomyopathy: a multinational collaboration. Circ Arrhythm Electrophysiol. 2021;14:e008509. PubMed PMC

Rigato I, Bauce B, Rampazzo A, Zorzi A, Pilichou K, Mazzotti E, et al. Compound and digenic heterozygosity predicts lifetime arrhythmic outcome and sudden cardiac death in desmosomal gene‐related arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet. 2013;6:533–42. PubMed

Bhonsale A, Groeneweg JA, James CA, Dooijes D, Tichnell C, Jongbloed JDH, et al. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy‐associated mutation carriers. Eur Heart J. 2015;36:847–55. PubMed

James CA, Bhonsale A, Tichnell C, Murray B, Russell SD, Tandri H, et al. Exercise increases age‐related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy‐associated desmosomal mutation carriers. J Am Coll Cardiol. 2013;62:1290–7. PubMed PMC

Sawant ACT, Riele ASJM, Tichnell C, Murray B, Bhonsale A, Tandri H, et al. Safety of American Heart Association‐recommended minimum exercise for desmosomal mutation carriers. Heart Rhythm. 2016;13:199–207. PubMed

Van Waning JI, Caliskan K, Hoedemaekers YM, Van Spaendonck‐Zwarts KY, Baas AF, Boekholdt SM, et al. Genetics, clinical features, and long‐term outcome of noncompaction cardiomyopathy. J Am Coll Cardiol. 2018;71:711–22. PubMed

Liu S, Bai Y, Huang J, Zhao H, Zhang X, Hu S, et al. Do mitochondria contribute to left ventricular non‐compaction cardiomyopathy? New findings from myocardium of patients with left ventricular non‐compaction cardiomyopathy. Mol Genet Metab. 2013;109:100–6. PubMed

Richard P, Ader F, Roux M, Donal E, Eicher JC, Aoutil N, et al. Targeted panel sequencing in adult patients with left ventricular non‐compaction reveals a large genetic heterogeneity. Clin Genet. 2019;95:356–67. PubMed

Vanlerberghe C, Jourdain A‐S, Ghoumid J, Frenois F, Mezel A, Vaksmann G, et al. Holt‐Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants. Eur J Hum Genet. 2019;27:360–8. PubMed PMC

Maury P, Gandjbakhch E, Baruteau A‐E, Bessière F, Kyndt F, Bouvagnet P, et al. Cardiac phenotype and long‐term follow‐up of patients with mutations in NKX2‐5 gene. J Am Coll Cardiol. 2016;68:2389–90. PubMed

Ross SB, Bagnall RD, Yeates L, Sy RW, Semsarian C. Holt‐Oram syndrome in two families diagnosed with left ventricular noncompaction and conduction disease. HeartRhythm Case Rep. 2018;4:146–51. PubMed PMC

Femia G, Zhu D, Choudhary P, Ross SB, Muthurangu V, Richmond D, et al. Long term clinical outcomes associated with CMR quantified isolated left ventricular non‐compaction in adults. Int J Cardiol. 2021;328:235–40. PubMed

Mazzarotto F, Hawley MH, Beltrami M, Beekman L, de Marvao A, McGurk KA, et al. Systematic large‐scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies. Genet Med. 2021;23:856–64. PubMed PMC

Ross SB, Semsarian C. Clinical and genetic complexities of left ventricular noncompaction: preventing overdiagnosis in a disease we do not understand. JAMA Cardiol. 2018;3:1033–4. PubMed

Ross SB, Jones K, Blanch B, Puranik R, McGeechan K, Barratt A, et al. A systematic review and meta‐analysis of the prevalence of left ventricular non‐compaction in adults. Eur Heart J. 2020;41:1428–36. PubMed

Gallego‐Delgado M, Delgado JF, Brossa‐Loidi V, Palomo J, Marzoa‐Rivas R, Perez‐Villa F, et al. Idiopathic restrictive cardiomyopathy is primarily a genetic disease. J Am Coll Cardiol. 2016;67:3021–3. PubMed

Kaski JP, Syrris P, Burch M, Tome‐Esteban MT, Fenton M, Christiansen M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart. 2008;94:1478–84. PubMed

Sen‐Chowdhry S, Syrris P, McKenna WJ. Genetics of restrictive cardiomyopathy. Heart Fail Clin. 2010;6:179–86. PubMed

Ton V‐K, Mukherjee M, Judge DP. Transthyretin cardiac amyloidosis: pathogenesis, treatments, and emerging role in heart failure with preserved ejection fraction. Clin Med Insights Cardiol. 2014;8(Suppl 1):39–44. PubMed PMC

Buxbaum JN, Ruberg FL. Transthyretin V122I (pV142I)* cardiac amyloidosis: an age‐dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans. Genet Med. 2017;19:733–42. PubMed PMC

Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, et al. Ten‐year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet. 2015;52:353–8. PubMed PMC

Emdin M, Aimo A, Rapezzi C, Fontana M, Perfetto F, Seferovic PM, et al. Treatment of cardiac transthyretin amyloidosis: an update. Eur Heart J. 2019;40:3699–706. PubMed

Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington‐Cruz M, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007–16. PubMed

Behr ER, Casey A, Sheppard M, Wright M, Bowker TJ, Davies MJ, et al. Sudden arrhythmic death syndrome: a national survey of sudden unexplained cardiac death. Heart. 2007;93:601–5. PubMed PMC

Lahrouchi N, Raju H, Lodder EM, Papatheodorou S, Miles C, Ware JS, et al. The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy. Eur J Hum Genet. 2020;28:17–22. PubMed PMC

de Noronha SV, Behr ER, Papadakis M, Ohta‐Ogo K, Banya W, Wells J, et al. The importance of specialist cardiac histopathological examination in the investigation of young sudden cardiac deaths. Europace. 2014;16:899–907. PubMed

Tester DJ, Medeiros‐Domingo A, Will ML, Haglund CM, Ackerman MJ. Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy‐negative sudden unexplained death referred for postmortem genetic testing. Mayo Clin Proc. 2012;87:524–39. PubMed PMC

Bagnall RD, Weintraub RG, Ingles J, Duflou J, Yeates L, Lam L, et al. A prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016;374:2441–52. PubMed

Lahrouchi N, Raju H, Lodder EM, Papatheodorou E, Ware JS, Papadakis M, et al. Utility of post‐mortem genetic testing in cases of sudden arrhythmic death syndrome. J Am Coll Cardiol. 2017;69:2134–45. PubMed PMC

Isbister JC, Nowak N, Butters A, Yeates L, Gray B, Sy RW, et al. "Concealed cardiomyopathy" as a cause of previously unexplained sudden cardiac arrest. Int J Cardiol. 2021;324:96–101. PubMed

Anderson JH, Tester DJ, Will ML, Ackerman MJ. Whole‐exome molecular autopsy after exertion‐related sudden unexplained death in the young. Circ Cardiovasc Genet. 2016;9:259–65. PubMed

Shanks GW, Tester DJ, Ackerman JP, Simpson MA, Behr ER, White SM, et al. Importance of variant interpretation in whole‐exome molecular autopsy: population‐based case series. Circulation. 2018;137:2705–15. PubMed

Grondin SD, Davies B, Cadrin‐Tourigny J, Steinberg C, Cheung CC, Jorda P, et al. Importance of genetic testing in unexplained cardiac arrest. Eur Heart J 2022;doi:10.1093/eurheartj/ehac145. PubMed PMC

Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998;98:2334–51. PubMed

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 United States. Circulation 1997;95:265–72. PubMed

Mellor G, Laksman ZWM, Tadros R, Roberts JD, Gerull B, Simpson CS, 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. 2017;10:e001686. PubMed

Asatryan B, Schaller A, Seiler J, Servatius H, Noti F, Baldinger SH, et al. Usefulness of genetic testing in sudden cardiac arrest survivors with or without previous clinical evidence of heart disease. Am J Cardiol. 2019;123:2031–8. PubMed

Visser M, Dooijes D, van der Smagt JJ, van der Heijden JF, Doevendans PA, Loh P, et al. Next‐generation sequencing of a large gene panel in patients initially diagnosed with idiopathic ventricular fibrillation. Heart Rhythm. 2017;14:1035–40. PubMed

Matassini MV, Krahn AD, Gardner M, Champagne J, Sanatani S, Birnie DH, et al. Evolution of clinical diagnosis in patients presenting with unexplained cardiac arrest or syncope due to polymorphic ventricular tachycardia. Heart Rhythm. 2014;11:274–81. PubMed

Alders M, Koopmann TT, Christiaans I, Postema PG, Beekman L, Tanck MW, et al. Haplotype‐sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation. Am J Hum Genet. 2009;84:468–76. PubMed PMC

Fujii Y, Itoh H, Ohno S, Murayama T, Kurebayashi N, Aoki H, et al. A type 2 ryanodine receptor variant associated with reduced Ca(2+) release and short‐coupled torsades de pointes ventricular arrhythmia. Heart Rhythm. 2017;14:98–107. PubMed

Li Y, Wei J, Guo W, Sun B, Estillore JP, Wang R, et al. Human RyR2 (Ryanodine Receptor 2) loss‐of‐function mutations: clinical phenotypes and in vitro characterization. Circ Arrhythm Electrophysiol. 2021;14:e010013. PubMed

Mone F, Stott BK, Hamilton S, Seale AN, Quinlan‐Jones E, Allen S, et al. The diagnostic yield of prenatal genetic technologies in congenital heart disease: a prospective cohort study. Fetal Diagn Ther. 2021;1–8. PubMed

Qiao F, Wang Y, Zhang C, Zhou R, Wu Y, Wang C, et al. Comprehensive evaluation of genetic variants in fetuses with congenital heart defect using chromosomal microarray analysis and exome sequencing. Ultrasound Obstet Gynecol. 2021;58:377–87. PubMed

Mone F, Eberhardt RY, Morris RK, Hurles ME, McMullan DJ, Maher ER, et al. COngenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: prospective cohort study and systematic review. Ultrasound Obstet Gynecol. 2021;57:43–51. PubMed

Hanchard NA, Umana LA, D'Alessandro L, Azamian M, Poopola M, Morris SA, et al. Assessment of large copy number variants in patients with apparently isolated congenital left‐sided cardiac lesions reveals clinically relevant genomic events. Am J Med Genet A. 2017;173:2176–88. PubMed PMC

Hauser NS, Solomon BD, Vilboux T, Khromykh A, Baveja R, Bodian DL. Experience with genomic sequencing in pediatric patients with congenital cardiac defects in a large community hospital. Mol Genet Genomic Med. 2018;6:200–12. PubMed PMC

Brunelli L, Jenkins SM, Gudgeon JM, Bleyl SB, Miller CE, Tvrdik T, et al. Targeted gene panel sequencing for the rapid diagnosis of acutely ill infants. Mol Genet Genomic Med. 2019;7:e00796. PubMed PMC

Thienpont B, Mertens L, de Ravel T, Eyskens B, Boshoff D, Maas N, et al. Submicroscopic chromosomal imbalances detected by array‐CGH are a frequent cause of congenital heart defects in selected patients. Eur Heart J. 2007;28:2778–84. PubMed

Jin SC, Homsy J, Zaidi S, Lu Q, Morton S, DePalma SR, et al. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet. 2017;49:1593–601. PubMed PMC

Homsy J, Zaidi S, Shen Y, Ware JS, Samocha KE, Karczewski KJ, et al. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science. 2015;350:1262–6. PubMed PMC

Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH, Thienpont B, et al. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat Genet. 2016;48:1060–5. PubMed PMC

Alankarage D, Ip E, Szot JO, Munro J, Blue GM, Harrison K, et al. Identification of clinically actionable variants from genome sequencing of families with congenital heart disease. Genet Med. 2019;21:1111–20. PubMed

Jia Y, Louw JJ, Breckpot J, Callewaert B, Barrea C, Sznajer Y, et al. The diagnostic value of next generation sequencing in familial nonsyndromic congenital heart defects. Am J Med Genet A 2015;167a:1822–9. PubMed

Blue GM, Kirk EP, Giannoulatou E, Dunwoodie SL, Ho JW, Hilton DC, et al. Targeted next‐generation sequencing identifies pathogenic variants in familial congenital heart disease. J Am Coll Cardiol. 2014;64:2498–506. PubMed

LaHaye S, Corsmeier D, Basu M, Bowman JL, Fitzgerald‐Butt S, Zender G, et al. Utilization of whole exome sequencing to identify causative mutations in familial congenital heart disease. Circ Cardiovasc Genet. 2016;9:320–9. PubMed PMC

Breckpot J, Thienpont B, Arens Y, Tranchevent LC, Vermeesch JR, Moreau Y, et al. Challenges of interpreting copy number variation in syndromic and non‐syndromic congenital heart defects. Cytogenet Genome Res. 2011;135:251–9. PubMed

Liu H, Giguet‐Valard AG, Simonet T, Szenker‐Ravi E, Lambert L, Vincent‐Delorme C, et al. Next‐generation sequencing in a series of 80 fetuses with complex cardiac malformations and/or heterotaxy. Hum Mutat. 2020;41:2167–78. PubMed

Li AH, Hanchard NA, Azamian M, D’Alessandro LCA, Coban‐Akdemir Z, Lopez KN, et al. Genetic architecture of laterality defects revealed by whole exome sequencing. Eur J Hum Genet. 2019;27:563–73. PubMed PMC

Gileles‐Hillel A, Mor‐Shaked H, Shoseyov D, Reiter J, Tsabari R, Hevroni A, et al. Whole‐exome sequencing accuracy in the diagnosis of primary ciliary dyskinesia. ERJ Open Res. 2020;6:00213–2020. PubMed PMC

Boskovski MT, Homsy J, Nathan M, Sleeper LA, Morton S, Manheimer KB, et al. De novo damaging variants, clinical phenotypes, and post‐operative outcomes in congenital heart disease. Circ Genom Precis Med. 2020;13:e002836. PubMed PMC

Ellesøe SG, Johansen MM, Bjerre JV, Hjortdal VE, Brunak S, Larsen LA. Familial atrial septal defect and sudden cardiac death: identification of a novel NKX2‐5 mutation and a review of the literature. Congenit Heart Dis. 2016;11:283–90. PubMed PMC

Li QY, Newbury‐Ecob RA, Terrett JA, Wilson DI, Curtis AR, Yi CH, et al. Holt‐Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet. 1997;15:21–9. PubMed

Blue GM, Smith J, Sholler GF, Semsarian C, Winlaw DS, Flagship AGCGD. Current practice of genetic testing and counselling in congenital heart disease: an Australian perspective. Heart Lung Circ. 2020;29:1733–6. PubMed

Zhang TN, Wu QJ, Liu YS, Lv JL, Sun H, Chang Q, et al. Environmental risk factors and congenital heart disease: an umbrella review of 165 systematic reviews and meta‐analyses with more than 120 million participants. Front Cardiovasc Med. 2021;8:640729. PubMed PMC

Geng J, Picker J, Zheng Z, Zhang X, Wang J, Hisama F, et al. Chromosome microarray testing for patients with congenital heart defects reveals novel disease causing loci and high diagnostic yield. BMC Genomics. 2014;15:1127. PubMed PMC

Szot JO, Cuny H, Blue GM, Humphreys DT, Ip E, Harrison K, et al. A screening approach to identify clinically actionable variants causing congenital heart disease in exome data. Circ Genom Precis Med. 2018;11:e001978. PubMed

Lander J, Ware SM. Copy number variation in congenital heart defects. Curr Genet Med Rep. 2014;2:168–78.

Powis Z, Thrush D, Davis BT, Dolinsky JS. Diagnostic exome sequencing in pediatric patients with congenital heart disease. J Am Coll Cardiol. 2016;67:991.

Morrish AM, Smith J, Enriquez A, Sholler GF, Mervis J, Dunwoodie SL, et al. A new era of genetic testing in congenital heart disease: a review. Trends Cardiovasc Med 2021;doi: 10.1016/j.tcm2021.04.011. PubMed

Richardson A, Ormond KE. Ethical considerations in prenatal testing: genomic testing and medical uncertainty. Semin Fetal Neonatal Med. 2018;23:161. PubMed

Iwarsson E, Jacobsson B, Dagerhamn J, Davidson T, Bernabé E, Heibert AM. Analysis of cell‐free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population—a systematic review and meta‐analysis. Acta Obstet Gynecol Scand. 2017;96:7–18. PubMed

Kagan KO, Sroka F, Sonek J, Abele H, Lüthgens K, Schmid M, et al. First‐trimester risk assessment based on ultrasound and cell‐free DNA vs combined screening: a randomized controlled trial. Ultrasound Obstet Gynecol. 2018;51:437–44. PubMed

Migliorini S, Saccone G, Silvestro F, Massaro G, Arduino B, D'Alessandro P, et al. First‐trimester screening based on cell‐free DNA vs combined screening: a randomized clinical trial on women's experience. Prenat Diagn. 2020;40:1482–8. PubMed

Russell MW, Chung WK, Kaltman JR, Miller TA. Advances in the understanding of the genetic determinants of congenital heart disease and their impact on clinical outcomes. JAHA. 2018;7:e006906. PubMed PMC

Zaidi S, Brueckner M. Genetics and genomics of congenital heart disease. Circ Res. 2017;120:923–40. PubMed PMC

Hureaux M, Guterman S, Hervé B, Till M, Jaillard S, Redon S, et al. Chromosomal microarray analysis in fetuses with an isolated congenital heart defect: A retrospective, nationwide, multicenter study in France. Prenat Diagn. 2019;39:464–70. PubMed

van Nisselrooij AEL, Lugthart MA, Clur SA, Linskens IH, Pajkrt E, Rammeloo LA, et al. The prevalence of genetic diagnoses in fetuses with severe congenital heart defects. Genet Med. 2020;22:1206–14. PubMed PMC

Landstrom AP, Kim JJ, Gelb BD, Helm BM, Kannankeril PJ, Semsarian C, et al. Genetic testing for heritable cardiovascular diseases in pediatric patients: a scientific statement from the American Heart Association. Circ Genom Precis Med. 2021;14:e000086. PubMed PMC

Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell. 2015;161:161–72. PubMed PMC

Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, Roos C, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358:1240–9. PubMed

Myocardial Infarction Genetics C, Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, et al. Genome‐wide association of early‐onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334–41. PubMed PMC

Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377:111–21. PubMed PMC

Inouye M, Abraham G, Nelson CP, Wood AM, Sweeting MJ, Dudbridge F et al; UK Biobank CardioMetabolic Consortium CHD Working Group. Genomic risk prediction of coronary artery disease in 480,000 adults: implications for primary prevention. J Am Coll Cardiol 2018;72:1883–93. PubMed PMC

Mosley JD, Gupta DK, Tan J, Yao J, Wells QS, Shaffer CM, et al. Predictive accuracy of a polygenic risk score compared with a clinical risk score for incident coronary heart disease. JAMA. 2020;323:627–35. PubMed PMC

Elliott J, Bodinier B, Bond TA, Chadeau‐Hyam M, Evangelou E, Moons KGM, et al. Predictive accuracy of a polygenic risk score‐enhanced prediction model vs a clinical risk score for coronary artery disease. JAMA. 2020;323:636–45. PubMed PMC

Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield M, Devlin JJ, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. 2015;385:2264–71. PubMed PMC

Bongianino R, Priori SG. Gene therapy to treat cardiac arrhythmias. Nat Rev Cardiol. 2015;12:531–46. PubMed

Matsa LS, Sagurthi SR, Ananthapur V, Nalla S, Nallari P. Endothelin 1 gene as a modifier in dilated cardiomyopathy. Gene. 2014;548:256–62. PubMed

Jiang J, Wakimoto H, Seidman JG, Seidman CE. Allele‐specific silencing of mutant Myh6 transcripts in mice suppresses hypertrophic cardiomyopathy. Science. 2013;342:111–4. PubMed PMC

Anzalone AV, Koblan LW, Liu DR. Genome editing with CRISPR‐Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol. 2020;38:824–44. PubMed

Dotzler SM, Kim CSJ, Gendron WAC, Zhou W, Ye D, Bos JM, et al. Suppression‐replacement KCNQ1 gene therapy for type 1 long QT syndrome. Circulation. 2021;143:1411–25. PubMed

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