title: Nature and Nurture in Arrhythmogenic Right Ventricular Cardiomyopathy - A Clinical Perspective.
abstract: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterised by frequent ventricular arrhythmias and slowly progressive predominant RV dysfunction. Up to two-thirds of ARVD/C patients have mutations in genes encoding the cardiac desmosome. Mutations in other genes are increasingly recognised. Inheritance of ARVD/C is generally autosomal dominant with reduced age-related penetrance and significant variable expressivity. While the full explanation for this phenotypic heterogeneity remains unclear, there is increasing evidence that exercise plays a major role in disease penetrance and arrhythmic risk. The disproportionate representation of athletes among ARVD/C patients has long been noted. Recently, the association of exercise with earlier onset and more severe arrhythmic and structural disease has been documented. This article reviews current evidence regarding the association of genotype, exercise and clinical outcomes and discusses the emerging paradigm in which genetic predisposition and environmental factors (exercise) interact around a threshold for phenotypic expression of ARVD/C.
authors.affiliation: Division of Cardiology, Johns Hopkins University, Baltimore, Maryland, US.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
keywords: Arrhythmogenic right ventricular dysplasia; arrhythmia; arrhythmogenic right ventricular cardiomyopathy; desmosome; exercise; genetics
references.citation: Circulation. 2004 Jun 8;109(22):2807-16
references.pmid: 15184297
references.citation: Circ Cardiovasc Genet. 2015 Jun;8(3):437-46
references.pmid: 25820315
references.citation: Eur Heart J. 2015 Apr 7;36(14):847-55
references.pmid: 25616645
references.citation: Heart. 2010 Aug;96(16):1268-74
references.pmid: 20525856
references.citation: JAMA. 2006 Oct 4;296(13):1593-601
references.pmid: 17018804
references.citation: Curr Opin Cardiol. 1995 Jan;10(1):16-20
references.pmid: 7787258
references.citation: Nat Genet. 2004 Nov;36(11):1162-4
references.pmid: 15489853
references.citation: Eur Heart J. 2012 May;33(9):1128-36
references.pmid: 22199124
references.citation: Eur Heart J. 2015 Jul 14;36(27):1735-43
references.pmid: 25896080
references.citation: Med Sci Sports Exerc. 2007 Aug;39(8):1423-34
references.pmid: 17762377
references.citation: Circulation. 2007 Apr 3;115(13):1710-20
references.pmid: 17372169
references.citation: Cardiovasc Res. 2005 Feb 1;65(2):366-73
references.pmid: 15639475
references.citation: Circ Cardiovasc Genet. 2013 Dec;6(6):552-6
references.pmid: 24125834
references.citation: Eur Heart J. 2010 Apr;31(7):806-14
references.pmid: 20172912
references.citation: Circulation. 2006 Oct 24;114(17):1799-806
references.pmid: 17030684
references.citation: Neth Heart J. 2013 Jun;21(6):286-93
references.pmid: 23568436
references.citation: Hum Mol Genet. 2010 Dec 1;19(23):4595-607
references.pmid: 20829228
references.citation: J Am Coll Cardiol. 2006 Oct 3;48(7):1416-24
references.pmid: 17010805
references.citation: Cardiovasc Res. 2014 Nov 1;104(2):280-9
references.pmid: 25253076
references.citation: Eur J Heart Fail. 2015 Feb;17(2):128-31
references.pmid: 25557220
references.citation: Hum Mutat. 2015 Apr;36(4):403-10
references.pmid: 25676813
references.citation: J Am Coll Cardiol. 2013 Oct 1;62(14):1290-7
references.pmid: 23871885
references.citation: Circulation. 2005 Aug 2;112(5):636-42
references.pmid: 16061754
references.citation: Herz. 2014 Mar;39(2):271-5
references.pmid: 24317018
references.citation: Am J Hum Genet. 2006 Jul;79(1):136-42
references.pmid: 16773573
references.citation: J Am Coll Cardiol. 2003 Dec 3;42(11):1959-63
references.pmid: 14662259
references.citation: J Am Heart Assoc. 2014 Dec;3(6):e001471
references.pmid: 25516436
references.citation: Circulation. 2011 Aug 23;124(8):876-85
references.pmid: 21810661
references.citation: Circ Cardiovasc Genet. 2013 Dec;6(6):525-7
references.pmid: 24347616
references.citation: J Am Coll Cardiol. 1988 Nov;12(5):1222-8
references.pmid: 3170963
references.citation: Eur Heart J. 2013 Jan;34(3):201-10
references.pmid: 23136403
references.citation: Circulation. 2005 Dec 20;112(25):3823-32
references.pmid: 16344387
references.citation: Am J Hum Genet. 2006 Nov;79(5):978-84
references.pmid: 17033975
references.citation: Br J Sports Med. 2012 Nov;46 Suppl 1:i44-50
references.pmid: 23097479
references.citation: Lancet. 2009 Apr 11;373(9671):1289-300
references.pmid: 19362677
references.citation: Br Heart J. 1986 Oct;56(4):321-6
references.pmid: 2945574
references.citation: Am J Hum Genet. 2008 Apr;82(4):809-21
references.pmid: 18313022
references.citation: J Am Coll Cardiol. 2008 Dec 16;52(25):2175-87
references.pmid: 19095136
references.citation: Lancet. 2000 Jun 17;355(9221):2119-24
references.pmid: 10902626
references.citation: Am J Cardiol. 2015 Oct 15;116(8):1245-51
references.pmid: 26310507
references.citation: Eur J Cardiovasc Prev Rehabil. 2006 Dec;13(6):876-85
references.pmid: 17143118
references.citation: Circulation. 1982 Feb;65(2):384-98
references.pmid: 7053899
references.citation: J Am Coll Cardiol. 2005 Apr 19;45(8):1364-7
references.pmid: 15837288
references.citation: Circulation. 2015 Aug 4;132(5):441-53
references.pmid: 26216213
references.citation: Eur J Heart Fail. 2012 Nov;14(11):1199-207
references.pmid: 22820313
references.citation: Am J Hum Genet. 2002 Nov;71(5):1200-6
references.pmid: 12373648
references.citation: Can J Cardiol. 2015 Nov;31(11):1313-24
references.pmid: 26199027
references.citation: Hum Mutat. 2006 Nov;27(11):1157
references.pmid: 17041889
references.citation: JACC Cardiovasc Imaging. 2015 Jul;8(7):863-4
references.pmid: 25457767
references.citation: Europace. 2014 Dec;16(12):1838-46
references.pmid: 24938629
references.citation: Genet Med. 2015 May;17(5):405-24
references.pmid: 25741868
references.citation: Eur Heart J. 2003 Aug;24(16):1473-80
references.pmid: 12919770
references.citation: Circ J. 2015;79(5):901-13
references.pmid: 25877738
references.citation: Heart Rhythm. 2016 Jan;13(1):199-207
references.pmid: 26321091
references.citation: Radiographics. 2014 Oct;34(6):1553-70
references.pmid: 25310417
references.citation: Trends Cardiovasc Med. 2014 Jul;24(5):184-90
references.pmid: 24656989
references.citation: Circ Cardiovasc Genet. 2013 Dec;6(6):533-42
references.pmid: 24070718
references.citation: Neth Heart J. 2014 Aug;22(7-8):316-25
references.pmid: 24817548
references.citation: J Am Coll Cardiol. 2010 Feb 9;55(6):587-97
references.pmid: 20152563
references.citation: Clin Genet. 2013 Apr;83(4):321-31
references.pmid: 22725725
references.citation: J Am Coll Cardiol. 2005 Apr 19;45(8):1340-5
references.pmid: 15837284
references.citation: J Am Coll Cardiol. 2011 Jun 7;57(23):2317-27
references.pmid: 21636032
references.citation: N Engl J Med. 1988 Jan 21;318(3):129-33
references.pmid: 3336399
references.citation: Hum Mol Genet. 2001 Feb 1;10(3):189-94
references.pmid: 11159936
references.citation: Eur J Heart Fail. 2014 Dec;16(12 ):1337-44
references.pmid: 25319773