Arrhythmogenic right ventricular cardiomyopathy: an overview and update
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Published
Jul 2, 2017
Abstract
Arrhythmogenic right ventricular cardiomyopathy consists in partial or total progressive replacement of cardiac muscle fibers with a fibro-adipose tissue. This is a hereditary disease with an autosomal dominant inheritance with incomplete penetrance and variable expressivity, except two autosomal recessive syndromes. The most frequent abnormal proteins are that of desmosomal intercellular junctions, such as junctional plakoglobin, plakophilin-2, desmoplakin, desmoglein-2, and desmocollin-2, although other types of non-desmosomal components may be also involved. Desmosomal disorders result in myocardial fibers necrosis and their progressive replacement with fibro-adipose tissue. The morphological modifications are usually beginning in the subepicardial layer and develop towards the endocardium, being associated with the ventricular wall degeneration, thinning, and progressive increase of the amount of adipose tissue. The average age of clinical manifestations onset is around 30-40 years old, with ventricular arrhythmia and high risk of sudden death. Currently, the diagnosis is based on the 2010 Task Force Diagnostic criteria. The current review presents an overview on traditional knowledge about this disease, adding updated information regarding molecular and genetic data. The knowledge of this disease is important for medical practice as a possible cause of arrhythmia and sudden death and its prognosis might be improved by appropiate genetic testing as family screening.
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Keywords
ventricular arrhythmias, cardiomyopathy, dysplasia
References
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2. Segall HN. Parchment heart (Osler). Am Heart J 1950; 40(6):948–950.
3. Uhl HS. A previously underscribed congenital malformation of the heart: Almost total absence of the myocardium of the right ventricle. Bull Johns Hopkins Hosp 1952; 91:197-209.
4. Marcus FI, Fontaine GH, Guiraudon G, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation 1982; 65(2):384–398.
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6. Protonotarios N, Tsatsopoulou A, Patsourakos P, et al. Cardiac abnormalities in familial palmoplantar keratosis. Br Heart J 1986; 56(4):321–326.
7. Rampazzo A, Nava A, Malacrida S, et al. Mutation in human desmoplakin domain binding to plakoglob in causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 2002; 71(5):1200–1206.
8. McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia cardiomyopathy. Br Heart J 1994; 71(3):215–218.
9. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 2010; 121(13):1533–1541.
10. Ross MH, Pawlina W. Histology: a Text and Atlas: with correlated cell and molecular biology. 7th edition. Wolters Kluwer, 2015.
11. Ohno S. The genetic background of arrhythmogenic right ventricular cardiomyopathy. J Arrhythm 2016; 32(5):398-403.
12. Orgeron GM, Calkins H. Advances in the Diagnosis and Management of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Curr Cardiol Rep 2016; 18(6):53.
13. Lahtinen AM, Lehtonen E, Marjamaa A, et al. Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm 2011; 8(8):1214-1221.
14. Francés RJ. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. A review and update. Int J Cardiol 2006; 110(3):279-287.
15. Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet J Rare Dis 2007; 14(2):45.
16. Tabib A, Loire R, Chalabreysse L, et al. Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia. Circulation 2003; 108(24):3000–3005.
17. Butcovan D, Amalinei C, Grigoriu C. Arrhythmogenic right ventricular cardiomyopathy – cause of sudden death in young people. Rom J Leg Med 2011; 19:189-194.
18. Azaouagh A, Churzidse S, Konorza T, et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol 2011; 100(5):383–394.
19. Groeneweg J, Bhonsale A, James 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(3):437-446.
20. Calkins H. Arrhythmogenic right ventricular dysplasia/cardiomyopathy-three decades of progress. Circ J 2015; 79(5):901-913.
21. Dalal D, Nasir K, Bomma C, et al. Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation 2005; 112(25):3823-3832.
22. Murray B. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a review of molecular and clinical literature. J Genet Couns 2012; 21(4):494-504.
23. McKoy G, Protonotarios N, Crosby A, et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 2000; 355(9221):2119-2124.
24. Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 2000; 9(18):1276-2761.
25. Te Riele AS, Hauer RN. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical challenges in a changing disease spectrum. Trends Cardiovasc Med 2015; 25(3):191-198.
26. Orgeron GM, Crosson JE. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. Cardiol Young 2017; 27(S1):S57-S61.
27. Zareba W. Quantifying Disease Progression in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Key to Advancing Therapy. JAMA Cardiol 2017; 11.
28. Bhuiyan ZA, Jongbloed JD, van der Smagt J, et al. Desmoglein-2 and desmocollin-2 mutations in Dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study. Circ Cardiovasc Genet 2009; 2(5):418-427.
29. Kapplinger JD, Landstrom AP, Salisbury BA, et al. Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 2011; 57(23):2317-2327.
30. Bhonsale A, Groeneweg JA, James CA. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers. Eur Heart J 2015; 36(14):847-855.
31. Rigato I, Bauce B, Rampazzo A, et al. Compound and digenic heterozygosity predicts life-time arrhythmic outcome and sudden cardiac death in desmosomal gene-related arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet 2013; 6(6):533-542.
32. Vanderschuren KL, Sieverink T, Wilders R. Arrhythmogenic right ventricular dysplasia/cardiomyopathy type 1: a light on molecular mechanisms. Genet Res Int 2013; 2013:460805.
33. Rampazzo A, Nava A, Danieli GA, et al. The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q24. Hum Mol Genet 1994; 3(6):959-962.
34. Beffagna G, Occhi G, Nava A, et al. Regulatory mutations in transforming growth factor-β3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res 2005; 65(2):366-373.
35. Basso C, Thiene G, Corrado D, et al. Arrhythmogenic right ventricular cardiomyopathy: dysplasia, dystrophy, or myocarditis? Circulation 1996; 94(5):983–999.
36. Asimaki A, Tandri H, Duffy ER, et al. Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2011; 4(5):743–752.
37. Campuzano O, Alcalde M, Iglesias A, et al. Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation. J Clin Pathol 2012; 65(12):1077-1783.
38. Calabrese F, Basso C, Carturan E, et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for viruses? Cardiovasc Pathol 2006; 15(1):11-17.
39. Bowles NE, Ni J, Marcus F, et al. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol 2002; 39(5):892–895.
40. Garcia-Gras E, Lombardi R, Giocondo MJ, et al. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest 2006; 116(7):2012–2021.
41. Philips B, Cheng A. 2015 update on the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy. Curr Opin Cardiol 2016; 31(1):46-56.
42. Roberts WC, Ko JM, Kuiper JJ, et al. Some previously neglected examples of arrhythmogenic right ventricular dysplasia/cardiomyopathy and frequency of its various reported manifestations. Am J Cardiol 2010; 106(2):268–274.
43. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J 2010; 31(7):806-814.
44. Asimaki A, Tandri H, Huang H, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med 2009; 360(11):1075–1084.
45. McKenna WJ, Thiene G, Nava A, et al. 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(3):215-218.
46. Philips B, Madhavan S, James C, et al. High prevalence of catecholamine-facilitated focal ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Arrhythm Electrophysiol 2013; 6(1):160–166.
47. Denis A, Sacher F, Derval N, et al. Diagnostic value of isoproterenol testing in arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2014; 7(4):590–597.
48. Kapplinger JD, LandstromAP, Salisbury BA, et al. Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 2011; 57(23):2317–2327.
49. Kircher M, Witten DM, Jain P, et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 2014; 46(3):310–315.
2. Segall HN. Parchment heart (Osler). Am Heart J 1950; 40(6):948–950.
3. Uhl HS. A previously underscribed congenital malformation of the heart: Almost total absence of the myocardium of the right ventricle. Bull Johns Hopkins Hosp 1952; 91:197-209.
4. Marcus FI, Fontaine GH, Guiraudon G, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation 1982; 65(2):384–398.
5. Gerlis LM, Schmidt-Ott SC, Ho SY, et al. Dysplastic conditions of the right ventricular myocardium: Uhls anomaly vs arrhythmogenic right ventricular dysplasia. Br Heart J 1993; 69(2):142–150.
6. Protonotarios N, Tsatsopoulou A, Patsourakos P, et al. Cardiac abnormalities in familial palmoplantar keratosis. Br Heart J 1986; 56(4):321–326.
7. Rampazzo A, Nava A, Malacrida S, et al. Mutation in human desmoplakin domain binding to plakoglob in causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 2002; 71(5):1200–1206.
8. McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia cardiomyopathy. Br Heart J 1994; 71(3):215–218.
9. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 2010; 121(13):1533–1541.
10. Ross MH, Pawlina W. Histology: a Text and Atlas: with correlated cell and molecular biology. 7th edition. Wolters Kluwer, 2015.
11. Ohno S. The genetic background of arrhythmogenic right ventricular cardiomyopathy. J Arrhythm 2016; 32(5):398-403.
12. Orgeron GM, Calkins H. Advances in the Diagnosis and Management of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Curr Cardiol Rep 2016; 18(6):53.
13. Lahtinen AM, Lehtonen E, Marjamaa A, et al. Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm 2011; 8(8):1214-1221.
14. Francés RJ. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. A review and update. Int J Cardiol 2006; 110(3):279-287.
15. Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet J Rare Dis 2007; 14(2):45.
16. Tabib A, Loire R, Chalabreysse L, et al. Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia. Circulation 2003; 108(24):3000–3005.
17. Butcovan D, Amalinei C, Grigoriu C. Arrhythmogenic right ventricular cardiomyopathy – cause of sudden death in young people. Rom J Leg Med 2011; 19:189-194.
18. Azaouagh A, Churzidse S, Konorza T, et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol 2011; 100(5):383–394.
19. Groeneweg J, Bhonsale A, James 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(3):437-446.
20. Calkins H. Arrhythmogenic right ventricular dysplasia/cardiomyopathy-three decades of progress. Circ J 2015; 79(5):901-913.
21. Dalal D, Nasir K, Bomma C, et al. Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation 2005; 112(25):3823-3832.
22. Murray B. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a review of molecular and clinical literature. J Genet Couns 2012; 21(4):494-504.
23. McKoy G, Protonotarios N, Crosby A, et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 2000; 355(9221):2119-2124.
24. Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 2000; 9(18):1276-2761.
25. Te Riele AS, Hauer RN. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical challenges in a changing disease spectrum. Trends Cardiovasc Med 2015; 25(3):191-198.
26. Orgeron GM, Crosson JE. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. Cardiol Young 2017; 27(S1):S57-S61.
27. Zareba W. Quantifying Disease Progression in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Key to Advancing Therapy. JAMA Cardiol 2017; 11.
28. Bhuiyan ZA, Jongbloed JD, van der Smagt J, et al. Desmoglein-2 and desmocollin-2 mutations in Dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study. Circ Cardiovasc Genet 2009; 2(5):418-427.
29. Kapplinger JD, Landstrom AP, Salisbury BA, et al. Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 2011; 57(23):2317-2327.
30. Bhonsale A, Groeneweg JA, James CA. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers. Eur Heart J 2015; 36(14):847-855.
31. Rigato I, Bauce B, Rampazzo A, et al. Compound and digenic heterozygosity predicts life-time arrhythmic outcome and sudden cardiac death in desmosomal gene-related arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet 2013; 6(6):533-542.
32. Vanderschuren KL, Sieverink T, Wilders R. Arrhythmogenic right ventricular dysplasia/cardiomyopathy type 1: a light on molecular mechanisms. Genet Res Int 2013; 2013:460805.
33. Rampazzo A, Nava A, Danieli GA, et al. The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q24. Hum Mol Genet 1994; 3(6):959-962.
34. Beffagna G, Occhi G, Nava A, et al. Regulatory mutations in transforming growth factor-β3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res 2005; 65(2):366-373.
35. Basso C, Thiene G, Corrado D, et al. Arrhythmogenic right ventricular cardiomyopathy: dysplasia, dystrophy, or myocarditis? Circulation 1996; 94(5):983–999.
36. Asimaki A, Tandri H, Duffy ER, et al. Altered desmosomal proteins in granulomatous myocarditis and potential pathogenic links to arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2011; 4(5):743–752.
37. Campuzano O, Alcalde M, Iglesias A, et al. Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation. J Clin Pathol 2012; 65(12):1077-1783.
38. Calabrese F, Basso C, Carturan E, et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for viruses? Cardiovasc Pathol 2006; 15(1):11-17.
39. Bowles NE, Ni J, Marcus F, et al. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol 2002; 39(5):892–895.
40. Garcia-Gras E, Lombardi R, Giocondo MJ, et al. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest 2006; 116(7):2012–2021.
41. Philips B, Cheng A. 2015 update on the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy. Curr Opin Cardiol 2016; 31(1):46-56.
42. Roberts WC, Ko JM, Kuiper JJ, et al. Some previously neglected examples of arrhythmogenic right ventricular dysplasia/cardiomyopathy and frequency of its various reported manifestations. Am J Cardiol 2010; 106(2):268–274.
43. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J 2010; 31(7):806-814.
44. Asimaki A, Tandri H, Huang H, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med 2009; 360(11):1075–1084.
45. McKenna WJ, Thiene G, Nava A, et al. 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(3):215-218.
46. Philips B, Madhavan S, James C, et al. High prevalence of catecholamine-facilitated focal ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Arrhythm Electrophysiol 2013; 6(1):160–166.
47. Denis A, Sacher F, Derval N, et al. Diagnostic value of isoproterenol testing in arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2014; 7(4):590–597.
48. Kapplinger JD, LandstromAP, Salisbury BA, et al. Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 2011; 57(23):2317–2327.
49. Kircher M, Witten DM, Jain P, et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 2014; 46(3):310–315.
How to Cite
Grigoraș, A., Knieling, L. A., & Amălinei, C. (2017). Arrhythmogenic right ventricular cardiomyopathy: an overview and update. Archive of Clinical Cases, 4(2), Arch Clin Cases 2017; 4(2):56-66. https://doi.org/10.22551/2017.15.0402.10095
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How to Cite
Grigoraș, A., Knieling, L. A., & Amălinei, C. (2017). Arrhythmogenic right ventricular cardiomyopathy: an overview and update. Archive of Clinical Cases, 4(2), Arch Clin Cases 2017; 4(2):56-66. https://doi.org/10.22551/2017.15.0402.10095