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Arrhythmogenic Right Ventricular Cardiomyopathy Prevalence and Arrhythmic Outcomes in At-Risk Family Members: A Systematic Review and Meta-Analysis

Originally published Genomic and Precision Medicine. 2022;15


    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex cardiomyopathy with autosomal dominant inheritance and age-related incomplete penetrance, characterized by a high risk of sudden cardiac death. Recent professional consensus guidelines recommend clinical cardiac lifelong serial screening for at-risk family members refined only by age, but family genotype might influence necessary screening. Although numerous studies report prevalence of disease and arrhythmia in family members and explore predictors of penetrance and arrhythmic risk, a systematic review consolidating this evidence is lacking.


    We searched Medline (PubMed), Embase, The Cochrane Library, and Web of Science for studies that reported prevalence of (1) diagnosis of ARVC per 2010 Task Force Criteria and/or (2) sustained ventricular arrhythmias (VA) in at least 10 family members of definite patients with ARVC.


    We identified 41 studies, including 36 that reported diagnosis by Task Force Criteria and 22 VA. Meta-analysis of 1359 family members, from 13 unique cohorts showed an average prevalence estimate of 25% for diagnosis as per Task Force Criteria (95% CI, 0.15–0.35, I2=96.44%). Overall prevalence of VA among gene-positive family members was 18% (95% CI, 0.13–0.23, I2=33.25%) in 7 independent studies (n=597). Family genotype was a significant risk factor for diagnosis of both ARVC (odds ratio, 6.91 [95% CI, 1.27–37.70]; P=0.0005) and VA (odds ratio, 13.62 [95% CI, 0.91–204.13]; P=0.06). Male gender was not associated with disease prevalence (odds ratio, 1.18 [95% CI, 0.72–1.95]; P=0.42) or VA (odds ratio, 0.81 [95% CI, 0.51–1.29]; P=0.91).


    The prevalence of ARVC and VA in at-risk family members differs significantly based on family genotype. Although recent recommendations provide a guideline based only on age, we propose screening every 1 to 2 years for gene-positive family members and every 3 to 5 years for first-degree relatives of gene-elusive cases, as long as they are asymptomatic and not athletes.


    Supplemental Material is available at

    For Sources of Funding and Disclosures, see page 243.

    Correspondence: Cynthia A. James, PhD, CGC, Johns Hopkins ARVD Program - Blalock 545, 600 N Wolfe St, Baltimore, MD 21287. Email


    • 1. Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy.Lancet. 2009; 373:1289–1300. doi: 10.1016/S0140-6736(09)60256-7CrossrefMedlineGoogle Scholar
    • 2. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people.N Engl J Med. 1988; 318:129–133. doi: 10.1056/NEJM198801213180301CrossrefMedlineGoogle Scholar
    • 3. Finocchiaro G, Papadakis M, Robertus JL, Dhutia H, Steriotis AK, Tome M, Mellor G, Merghani A, Malhotra A, Behr E, et al.. Etiology of sudden death in sports: insights from a united kingdom regional registry.J Am Coll Cardiol. 2016; 67:2108–2115. doi: 10.1016/j.jacc.2016.02.062CrossrefMedlineGoogle Scholar
    • 4. Corrado D, van Tintelen PJ, McKenna WJ, Hauer RNW, Anastastakis A, Asimaki A, Basso C, Bauce B, Brunckhorst C, Bucciarelli-Ducci C, et al.; International Experts. Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis.Eur Heart J. 2020; 41:1414–1429. doi: 10.1093/eurheartj/ehz669MedlineGoogle Scholar
    • 5. James CA, Jongbloed JDH, Hershberger RE, Morales A, Judge DP, Syrris P, Pilichou K, Domingo AM, Murray B, Cadrin-Tourigny J, 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. doi: 10.1161/CIRCGEN.120.003273LinkGoogle Scholar
    • 6. Hershberger RE, Givertz MM, Ho CY, Judge DP, Kantor PF, McBride KL, Morales A, Taylor MRG, Vatta M, Ware SM. Genetic evaluation of cardiomyopathy-a heart failure society of america practice guideline.J Card Fail. 2018; 24:281–302. doi: 10.1016/j.cardfail.2018.03.004CrossrefMedlineGoogle Scholar
    • 7. Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, Daubert JP, de Chillou C, DePasquale EC, Desai MY, et al.. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.Heart Rhythm. 2019; 16:e301–e372. doi: 10.1016/j.hrthm.2019.05.007CrossrefMedlineGoogle Scholar
    • 8. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MG, Daubert JP, et al.. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria.Eur Heart J. 2010; 31:806–814. doi: 10.1093/eurheartj/ehq025CrossrefMedlineGoogle Scholar
    • 9. Groeneweg JA, Bhonsale A, James CA, te Riele AS, Dooijes D, Tichnell C, Murray B, Wiesfeld AC, Sawant AC, Kassamali B, 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; 8:437–446. doi: 10.1161/CIRCGENETICS.114.001003LinkGoogle Scholar
    • 10. Jurlander R, Mills HL, Espersen KI, Raja AA, Svendsen JH, Theilade J, Iversen K, Vejlstrup N, Bundgaard H, Christensen AH. Screening relatives in arrhythmogenic right ventricular cardiomyopathy: yield of imaging and electrical investigations.Eur Heart J Cardiovasc Imaging. 2020; 21:175–182. doi: 10.1093/ehjci/jez204MedlineGoogle Scholar
    • 11. Protonotarios N, Anastasakis A, Antoniades L, Chlouverakis G, Syrris P, Basso C, Asimaki A, Theopistou A, Stefanadis C, Thiene G, et al.. Arrhythmogenic right ventricular cardiomyopathy/dysplasia on the basis of the revised diagnostic criteria in affected families with desmosomal mutations.Eur Heart J. 2011; 32:1097–1104. doi: 10.1093/eurheartj/ehr043CrossrefMedlineGoogle Scholar
    • 12. Sawant AC, Te Riele AS, Tichnell C, Murray B, Bhonsale A, Tandri H, Judge DP, Calkins H, James CA. Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers.Heart Rhythm. 2016; 13:199–207. doi: 10.1016/j.hrthm.2015.08.035CrossrefMedlineGoogle Scholar
    • 13. La Gerche A, Robberecht C, Kuiperi C, Nuyens D, Willems R, de Ravel T, Matthijs G, Heidbüchel H. Lower than expected desmosomal gene mutation prevalence in endurance athletes with complex ventricular arrhythmias of right ventricular origin.Heart. 2010; 96:1268–1274. doi: 10.1136/hrt.2009.189621CrossrefMedlineGoogle Scholar
    • 14. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, Camerini F. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology.Br Heart J. 1994; 71:215–218. doi: 10.1136/hrt.71.3.215CrossrefMedlineGoogle Scholar
    • 15. Hamid MS, Norman M, Quraishi A, Firoozi S, Thaman R, Gimeno JR, Sachdev B, Rowland E, Elliott PM, McKenna WJ. Prospective evaluation of relatives for familial arrhythmogenic right ventricular cardiomyopathy/dysplasia reveals a need to broaden diagnostic criteria.J Am Coll Cardiol. 2002; 40:1445–1450. doi: 10.1016/s0735-1097(02)02307-0CrossrefMedlineGoogle Scholar
    • 16. Alcalde M, Campuzano O, Berne P, García-Pavía P, Doltra A, Arbelo E, Sarquella-Brugada G, Iglesias A, Alonso-Pulpon L, Brugada J, et al.. Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy.PLoS One. 2014; 9:e100560. doi: 10.1371/journal.pone.0100560CrossrefMedlineGoogle Scholar
    • 17. Chen L, Rao M, Chen X, Chen K, Ren J, Zhang N, Zhao Q, Yu W, Yuan B, Song J. A founder homozygous DSG2 variant in East Asia results in ARVC with full penetrance and heart failure phenotype.Int J Cardiol. 2019; 274:263–270. doi: 10.1016/j.ijcard.2018.06.105CrossrefMedlineGoogle Scholar
    • 18. Chivulescu M, Lie ØH, Popescu BA, Skulstad H, Edvardsen T, Jurcut RO, Haugaa KH. High penetrance and similar disease progression in probands and in family members with arrhythmogenic cardiomyopathy.Eur Heart J. 2020; 41:1401–1410. doi: 10.1093/eurheartj/ehz570CrossrefMedlineGoogle Scholar
    • 19. DeWitt ES, Chandler SF, Hylind RJ, Beausejour Ladouceur V, Blume ED, VanderPluym C, Powell AJ, Fynn-Thompson F, Roberts AE, et al.. Phenotypic manifestations of arrhythmogenic cardiomyopathy in children and adolescents.J Am Coll Cardiol. 2019; 74:346–358. doi: 10.1016/j.jacc.2019.05.022CrossrefMedlineGoogle Scholar
    • 20. Hall CL, Akhtar MM, Sabater-Molina M, Futema M, Asimaki A, Protonotarios A, Dalageorgou C, Pittman AM, Suarez MP, Aguilera B, et al.. Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype.Int J Cardiol. 2020; 307:101–108. doi: 10.1016/j.ijcard.2019.09.048CrossrefMedlineGoogle Scholar
    • 21. Heermann P, Hedderich DM, Paul M, Schülke C, Kroeger JR, Baeßler B, Wichter T, Maintz D, Waltenberger J, Heindel W, et al.. Biventricular myocardial strain analysis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) using cardiovascular magnetic resonance feature tracking.J Cardiovasc Magn Reson. 2014; 16:75. doi: 10.1186/s12968-014-0075-zCrossrefMedlineGoogle Scholar
    • 22. Hermida A, Fressart V, Hidden-Lucet F, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Mansencal N, Delacretaz E, et al.. High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.Eur J Heart Fail. 2019; 21:792–800. doi: 10.1002/ejhf.1423CrossrefMedlineGoogle Scholar
    • 23. Pilichou K, Lazzarini E, Rigato I, Celeghin R, De Bortoli M, Perazzolo Marra M, Cason M, Jongbloed J, Calore M, Rizzo S, et al.. Large genomic rearrangements of desmosomal genes in Italian arrhythmogenic cardiomyopathy patients.Circ Arrhythm Electrophysiol. 2017; 10:e005324. doi: 10.1161/CIRCEP.117.005324LinkGoogle Scholar
    • 24. Quarta G, Muir A, Pantazis A, Syrris P, Gehmlich K, Garcia-Pavia P, Ward D, Sen-Chowdhry S, Elliott PM, McKenna WJ. Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria.Circulation. 2011; 123:2701–2709. doi: 10.1161/CIRCULATIONAHA.110.976936LinkGoogle Scholar
    • 25. Svensson A, Åström-Aneq M, Widlund KF, Fluur C, Green A, Rehnberg M, Gunnarsson C. Arrhythmogenic right ventricular cardiomyopathy - 4 Swedish families with an associated PKP2 c.2146-1G>C variant.Am J Cardiovasc Dis. 2016; 6:55–65. Accessed May 19, 2022. Scholar
    • 26. te Riele AS, James CA, Groeneweg JA, Sawant AC, Kammers K, Murray B, Tichnell C, van der Heijden JF, Judge DP, Dooijes D, et al.. Approach to family screening in arrhythmogenic right ventricular dysplasia/cardiomyopathy.Eur Heart J. 2016; 37:755–763. doi: 10.1093/eurheartj/ehv387CrossrefMedlineGoogle Scholar
    • 27. Mast TP, Taha K, Cramer MJ, Lumens J, van der Heijden JF, Bouma BJ, van den Berg MP, Asselbergs FW, Doevendans PA, Teske AJ. The prognostic value of right ventricular deformation imaging in early arrhythmogenic right ventricular cardiomyopathy.JACC Cardiovasc Imaging. 2019; 12:446–455. doi: 10.1016/j.jcmg.2018.01.012CrossrefMedlineGoogle Scholar
    • 28. Bhonsale A, Groeneweg JA, James CA, Dooijes D, Tichnell C, Jongbloed JD, Murray B, te Riele AS, van den Berg MP, Bikker H, et al.. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers.Eur Heart J. 2015; 36:847–855. doi: 10.1093/eurheartj/ehu509CrossrefMedlineGoogle Scholar
    • 29. Campuzano O, Fernandez-Falgueras A, Sarquella-Brugada G, Cesar S, Arbelo E, García-Álvarez A, Jordà P, Coll M, Fiol V, Iglesias A, et al.. Personalized interpretation and clinical translation of genetic variants associated with cardiomyopathies.Front Genet. 2019; 10:450. doi: 10.3389/fgene.2019.00450CrossrefMedlineGoogle Scholar
    • 30. Cox MG, van der Zwaag PA, van der Werf C, van der Smagt JJ, Noorman M, Bhuiyan ZA, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, et al.. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study.Circulation. 2011; 123:2690–2700. doi: 10.1161/CIRCULATIONAHA.110.988287LinkGoogle Scholar
    • 31. te Riele AS, James CA, Rastegar N, Bhonsale A, Murray B, Tichnell C, Judge DP, Bluemke DA, Zimmerman SL, Kamel IR, et al.. Yield of serial evaluation in at-risk family members of patients with ARVD/C.J Am Coll Cardiol. 2014; 64:293–301. doi: 10.1016/j.jacc.2014.04.044CrossrefMedlineGoogle Scholar
    • 32. Saberniak J, Hasselberg NE, Borgquist R, Platonov PG, Sarvari SI, Smith HJ, Ribe M, Holst AG, Edvardsen T, Haugaa KH. Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members.Eur J Heart Fail. 2014; 16:1337–1344. doi: 10.1002/ejhf.181CrossrefMedlineGoogle Scholar
    • 33. Te Riele ASJM, James CA, Sawant AC, Bhonsale A, Groeneweg JA, Mast TP, Murray B, Tichnell C, Dooijes D, van Tintelen JP, et al.. Arrhythmogenic right ventricular dysplasia/cardiomyopathy in the pediatric population: clinical characterization and comparison with adult-onset disease.JACC Clin Electrophysiol. 2015; 1:551–560. doi: 10.1016/j.jacep.2015.08.004CrossrefMedlineGoogle Scholar
    • 34. James CA, Bhonsale A, Tichnell C, Murray B, Russell SD, Tandri H, Tedford RJ, Judge DP, Calkins H. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers.J Am Coll Cardiol. 2013; 62:1290–1297. doi: 10.1016/j.jacc.2013.06.033CrossrefMedlineGoogle Scholar
    • 35. Bhonsale A, James CA, Tichnell C, Murray B, Gagarin D, Philips B, Dalal D, Tedford R, Russell SD, Abraham T, et al.. Incidence and predictors of implantable cardioverter defibrillator therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing implantable cardioverter defibrillator implantation for primary prevention.J Am Coll Cardiol. 2011; 58:1485–1496. doi: 10.1016/j.jacc.2011.06.043CrossrefMedlineGoogle Scholar
    • 36. Leren IS, Saberniak J, Haland TF, Edvardsen T, Haugaa KH. Combination of ECG and echocardiography for identification of arrhythmic events in early ARVC.JACC Cardiovasc Imaging. 2017; 10:503–513. doi: 10.1016/j.jcmg.2016.06.011CrossrefMedlineGoogle Scholar
    • 37. Bhonsale A, James CA, Tichnell C, Murray B, Madhavan S, Philips B, Russell SD, Abraham T, Tandri H, Judge DP, et al.. Risk stratification in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers.Circ Arrhythm Electrophysiol. 2013; 6:569–578. doi: 10.1161/CIRCEP.113.000233LinkGoogle Scholar
    • 38. Lie ØH, Dejgaard LA, Saberniak J, Rootwelt C, Stokke MK, Edvardsen T, Haugaa KH. Harmful effects of exercise intensity and exercise duration in patients with arrhythmogenic cardiomyopathy.JACC Clin Electrophysiol. 2018; 4:744–753. doi: 10.1016/j.jacep.2018.01.010CrossrefMedlineGoogle Scholar
    • 39. Lie ØH, Rootwelt-Norberg C, Dejgaard LA, Leren IS, Stokke MK, Edvardsen T, Haugaa KH. Prediction of life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy: a primary prevention cohort study.JACC Cardiovasc Imaging. 2018; 11:1377–1386. doi: 10.1016/j.jcmg.2018.05.017CrossrefMedlineGoogle Scholar
    • 40. Mast TP, Teske AJ, Te Riele AS, Groeneweg JA, Van Der Heijden JF, Velthuis BK, Loh P, Doevendans PA, Van Veen TA, Dooijes D, et al.. Prolonged electromechanical interval unmasks arrhythmogenic right ventricular dysplasia/cardiomyopathy in the subclinical stage.J Cardiovasc Electrophysiol. 2016; 27:303–314. doi: 10.1111/jce.12882CrossrefMedlineGoogle Scholar
    • 41. Mast TP, Teske AJ, Walmsley J, van der Heijden JF, van Es R, Prinzen FW, Delhaas T, van Veen TA, Loh P, Doevendans PA, et al.. Right ventricular imaging and computer simulation for electromechanical substrate characterization in arrhythmogenic right ventricular cardiomyopathy.J Am Coll Cardiol. 2016; 68:2185–2197. doi: 10.1016/j.jacc.2016.08.061CrossrefMedlineGoogle Scholar
    • 42. Sarvari SI, Haugaa KH, Anfinsen OG, Leren TP, Smiseth OA, Kongsgaard E, Amlie JP, Edvardsen T. Right ventricular mechanical dispersion is related to malignant arrhythmias: a study of patients with arrhythmogenic right ventricular cardiomyopathy and subclinical right ventricular dysfunction.Eur Heart J. 2011; 32:1089–1096. doi: 10.1093/eurheartj/ehr069CrossrefMedlineGoogle Scholar
    • 43. Rootwelt-Norberg C, Lie ØH, Dejgaard LA, Chivulescu M, Leren IS, Edvardsen T, Haugaa KH. Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center.Int J Cardiol. 2019; 279:79–83. doi: 10.1016/j.ijcard.2018.12.066CrossrefMedlineGoogle Scholar
    • 44. Castrini AI, Lie ØH, Leren IS, Estensen ME, Stokke MK, Klæboe LG, Edvardsen T, Haugaa KH. Number of pregnancies and subsequent phenotype in a cross-sectional cohort of women with arrhythmogenic cardiomyopathy.Eur Heart J Cardiovasc Imaging. 2019; 20:192–198. doi: 10.1093/ehjci/jey061CrossrefMedlineGoogle Scholar
    • 45. Batchvarov VN, Bastiaenen R, Postema PG, Clark EN, Macfarlane PW, Wilde AA, Behr ER. Novel electrocardiographic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.Europace. 2016; 18:1420–1426. doi: 10.1093/europace/euv379CrossrefMedlineGoogle Scholar
    • 46. Baturova MA, Haugaa KH, Jensen HK, Svensson A, Gilljam T, Bundgaard H, Madsen T, Hansen J, Chivulescu M, Christiansen MK, et al.. Atrial fibrillation as a clinical characteristic of arrhythmogenic right ventricular cardiomyopathy: experience from the Nordic ARVC Registry.Int J Cardiol. 2020; 298:39–43. doi: 10.1016/j.ijcard.2019.07.086CrossrefMedlineGoogle Scholar
    • 47. Cox MG, van der Smagt JJ, Noorman M, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, Dooijes D, Houweling AC, Loh P, et al.. Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnostic task force criteria: impact of new task force criteria.Circ Arrhythm Electrophysiol. 2010; 3:126–133. doi: 10.1161/CIRCEP.109.927202LinkGoogle Scholar
    • 48. Mast TP, Teske AJ, vd Heijden JF, Groeneweg JA, Te Riele AS, Velthuis BK, Hauer RN, Doevendans PA, Cramer MJ. Left ventricular involvement in arrhythmogenic right ventricular dysplasia/cardiomyopathy assessed by echocardiography predicts adverse clinical outcome.J Am Soc Echocardiogr. 2015; 28:1103–1113.e9. doi: 10.1016/j.echo.2015.04.015CrossrefMedlineGoogle Scholar
    • 49. Rastegar N, Te Riele AS, James CA, Bhonsale A, Murray B, Tichnell C, Calkins H, Tandri H, Bluemke DA, Kamel IR, et al.. Fibrofatty changes: incidence at cardiac MR imaging in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.Radiology. 2016; 280:405–412. doi: 10.1148/radiol.2016150988CrossrefMedlineGoogle Scholar
    • 50. Réant P, Hauer AD, Castelletti S, Pantazis A, Rosmini S, Cheang MH, Peyrou J, Tomé-Esteban M, Syrris P, Lafitte S, et al.. Epicardial myocardial strain abnormalities may identify the earliest stages of arrhythmogenic cardiomyopathy.Int J Cardiovasc Imaging. 2016; 32:593–601. doi: 10.1007/s10554-015-0813-9CrossrefMedlineGoogle Scholar
    • 51. Teske AJ, Cox MG, Te Riele AS, De Boeck BW, Doevendans PA, Hauer RN, Cramer MJ. Early detection of regional functional abnormalities in asymptomatic ARVD/C gene carriers.J Am Soc Echocardiogr. 2012; 25:997–1006. doi: 10.1016/j.echo.2012.05.008CrossrefMedlineGoogle Scholar
    • 52. van der Zwaag PA, Cox MG, van der Werf C, Wiesfeld AC, Jongbloed JD, Dooijes D, Bikker H, Jongbloed R, Suurmeijer AJ, van den Berg MP, et al.. Recurrent and founder mutations in the netherlands: Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia.Neth Heart J. 2010; 18:583–591. doi: 10.1007/s12471-010-0839-5CrossrefMedlineGoogle Scholar
    • 53. James CA, Syrris P, van Tintelen JP, Calkins H. The role of genetics in cardiovascular disease: arrhythmogenic cardiomyopathy.Eur Heart J. 2020; 41:1393–1400. doi: 10.1093/eurheartj/ehaa141CrossrefMedlineGoogle Scholar
    • 54. Sawant AC, Bhonsale A, te Riele AS, Tichnell C, Murray B, Russell SD, Tandri H, Tedford RJ, Judge DP, Calkins H, et al.. Exercise has a disproportionate role in the pathogenesis of arrhythmogenic right ventricular dysplasia/cardiomyopathy in patients without desmosomal mutations.J Am Heart Assoc. 2014; 3:e001471. doi: 10.1161/JAHA.114.001471LinkGoogle Scholar
    • 55. Campuzano O, Alcalde M, Iglesias A, Barahona-Dussault C, Sarquella-Brugada G, Benito B, Arzamendi D, Flores J, Leung TK, Talajic M, et al.. Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation.J Clin Pathol. 2012; 65:1077–1083. doi: 10.1136/jclinpath-2012-201022CrossrefMedlineGoogle Scholar
    • 56. Bosman LP, Sammani A, James CA, Cadrin-Tourigny J, Calkins H, van Tintelen JP, Hauer RNW, Asselbergs FW, Te Riele ASJM. Predicting arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: a systematic review and meta-analysis.Heart Rhythm. 2018; 15:1097–1107. doi: 10.1016/j.hrthm.2018.01.031CrossrefMedlineGoogle Scholar
    • 57. Cadrin-Tourigny J, Bosman LP, Nozza A, Wang W, Tadros R, Bhonsale A, Bourfiss M, Fortier A, Lie ØH, Saguner AM, et al.. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.Eur Heart J. 2019; 40:1850–1858. doi: 10.1093/eurheartj/ehz103CrossrefMedlineGoogle Scholar
    • 58. Carruth ED, Beer D, Alsaid A, Schwartz MLB, McMinn M, Kelly MA, Buchanan AH, Nevius CD, Calkins H, James CA, et al.. Clinical findings and diagnostic yield of arrhythmogenic cardiomyopathy through genomic screening of pathogenic or likely pathogenic desmosome gene variants.Circ Genom Precis Med. 2021; 14:e003302. doi: 10.1161/CIRCGEN.120.003302LinkGoogle Scholar
    • 59. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al.. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ. 2021; 372:n71. doi: 10.1136/bmj.n71CrossrefMedlineGoogle Scholar
    • 60. Luchini C, Stubbs B, Solmi M, Veronese N. Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale.World J Meta-Anal. 2017; 5(4): 80–84. doi: 10.13105/wjma.v5.i4.80CrossrefGoogle Scholar