Arytmogenic ventricular cardiomyopathy

Czech version

Authors: Petr Tomášek ^1,2; Petra Dohnalová ¹; Tereza Kubíková ²; Milena Králíčková ²; Michal Beran ¹; Zbyněk Tonar ²
Authors‘ workplace: Ústav soudního lékařství 2. LF UK a Nemocnice Na Bulovce, Praha ¹; Ústav histologie a embryologie LF UK v Plzni ²
Published in: Soud Lék., 60, 2015, No. 4, p. 51-56
Category: Review

Overview

Arrhythmogenic ventricular cardiomyopathy is considered to be a primary cardiomyopathy. Over the last few decades, although being a relatively rare disease with its prevalence 1:2000 – 1:5000, there were numerous studies performed with the aim to elucidate the underlaying causes, pathogenesis, diagnostical aspects and possible treatment options of the disease. Arrhythmogenic ventricular cardiomyopathy is genetically conditioned disease where proteins of the cell-cell junctions are involved. Mutations of the myocardial intercalated dics proteins, mainly desmosomal proteins (e.g.plakoglobin), are held to be responsible for electromechanical instability of the myocardium which causes regressive changes in cardiomyocytes in most cases of arrhythmogenic ventricular cardiomyopathy. Subsequent morphological changes include fibrofatty replacement and inflammation of the myocardium. The condition results in structural changes of the heart hence arrhytmias and other signs of heart disease. There are 3 variants of this cardiomyopathy: ‚classical‘ variant with predominant right ventricular involvement, biventricular and variant with left ventricular predominance. Clinical findings in patients with arrhythmogenic ventricular cardiomyopathy suggested the most appropriate means of the diagnostics and helped to create Task Force Criteria for in vivo diagnosis of the disease. The major pitfall and significance of arrhythmogenic ventricular cardiomyopathy lies in its common presentation as sudden cardiac death affecting mostly young adults.

Keywords:
arrhythmogenic cardiomyopathy – intercalated disc – plakoglobin – desmosome – sudden death

Sources

1. Coonar AS, Protonotarios N, Tsatsopoulou A, et al. Gene for arrhythmogenic right ventricular cardiomyopathy with diffuse nonepidermolytic palmoplantar keratoderma and woolly hair (Naxos disease) maps to 17q21. Circulation 1998; 97: 2049–2058.

2. Herren T, Gerber PA, Duru F. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations. Clin Res Cardiol 2009; 98: 141–158.

3. Azaouagh A, Churzidse S, Konorza T, Erbel R. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol 2011; 100: 383–394.

4. Thiene G. Arrhythmogenic cardiomyopathy: from autopsy to genes and transgenic mice (SCVP Achievement Award Lecture, San Antonio, TX, February 27, 2011), Cardiovasc Pathol 2012; 21(4): 229-239.

5. Angelini A, Basso C, Nava A, Thiene G. Endomyocardial biopsy in arrhythmogenic right ventricular cardiomyopathy. Am Heart J 1996; 132: 203–206.

6. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 1996; 93: 841–842.

7. Šteiner I. Kardiopatologie. Praha: Galén; 2010: 51-52.

8. Saguner AM, Brunckhorst C, Duru F. Arrhythmogenic ventricular cardiomyopathy: A paradigm shift from right to biventricular disease. World J Cardiol 2014; 6(4): 154–174.

9. Ackerman MJ, Priori SG, Willems S, 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). Europace 2011; 13: 1077–1109.

10. Thiene G, Corrado D, Basso C. Cardiomyopathies: is it time for a molecular classification? Eur Heart J 2004; 25: 1772–1775.

11. Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807–1816.

12. Fressart V, Duthoit G, Donal E, et al. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace 2010; 12: 861–868.

13. Basso C, Czarnowska E, Della Barbera M, et al. Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. Eur Heart J 2006; 27: 1847-1854.

14. Delmar M, McKenna WJ. The cardiac desmosome and arrhythmogenic cardiomyopathies: from gene to disease. Circ Res 2010; 107: 700–714.

15. Sato PY, Coombs W, Lin X, et al. Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res 2011; 109: 193–201.

16. Gomes J, Finlay M, Ahmed AK, et al. Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study. Eur Heart J 2012; 33: 1942–1953.

17. Bauce B, Basso C, Rampazzo A, et al. Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations. Eur Heart J 2005; 26: 1666–1675.

18. Khan A, Mittal S, Sherrid MV. Arrhythmogenic right ventricular dysplasia: from genetics to treatment. Anadolu Kardiyol Derg 2009; 9(Suppl 2): 24–31.

19. McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Br Heart J 1994; 71: 215-218.

20. Matthes SA, Taffet S, Delmar M. Plakophilin-2 and the migration, differentiation and transformation of cells derived from the epicardium of neonatal rat hearts. Cell Commun Adhes 2011; 18: 73–84.

21. H Fischer A, van der Loo B, M Shär G, et al. Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy. Clin Cardiol 2008; 31: 469–471.

22. Bowles NE, Ni J, Marcus F, Towbin JA. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol 2002; 39: 892–895.

23. Basso C, Thiene G. Adipositas cordis, fatty infiltration of the right ventricle, and arrhythmogenic right ventricular cardiomyopathy. Just a matter of fat? Cardiovasc Pathol 2005; 14: 37-41

24. Corrado D, Basso C, Nava A, Rossi L, Thiene G. Sudden death in young people with apparently isolated mitral valve prolapse. G Ital Cardiol 1997; 27: 1097–1105.

25. 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: 3000–3005.

26. Marcus FI, Fontaine GH, Guiraudon G, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation 1982; 65: 384–398.

27. Te Riele AS, James CA, Philips B, et al. Mutation-positive arrhythmogenic right ventricular dysplasia/cardiomyopathy: the triangle of dysplasia displaced. J Cardiovasc Electrophysiol 2013; 24: 1311–1320.

28. Sen-Chowdhry S, Syrris P, Prasad SK, et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol 2008; 52: 2175–2187.

29. Kjaergaard J, Hastrup Svendsen J, Sogaard P, et al. Advanced quantitative echocardiography in arrhythmogenic right ventricular cardiomyopathy. J Am Soc Echocardiogr 2007; 20: 27–35.

30. Sen-Chowdhry S, Morgan RD, Chambers JC, McKenna WJ. Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment. Annu Rev Med 2010; 61: 233-253.

31. Basso C, Thiene G, Corrado D, Buja G, Melacini P, Nava A. Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia. Hum Pathol 2000; 31: 988–998.

32. Marcus FI, Fontaine G. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: a review. Pacing Clin Electrophysiol 1995; 18: 1298–1314.

33. Corrado D, Fontaine G, Marcus FI, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: need for an international registry. Study Group on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy of the Working Groups on Myocardial and Pericardial Disease and Arrhythmias of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the World Heart Federation. Circulation 2000; 101(11): E101-106.

34. Basso C, Thiene G, Corrado D, Angelini A, Nava A, Valente M. Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation 1996; 94(5): 983-991.

35. 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: 806-814.

36. Riele A, Tandri H, Bluemke D. Arrhythmogenic right ventricular cardiomyopathy (ARVC): cardiovascular magnetic resonance update, J Cardiovasc Magn Reson 2014; 16(1): 50.

37. Tavora F, Zhang M, Cresswell M, Li L, Fowler D, Franco M, Burke A. Quantitative Immunohistochemistry of Desmosomal Proteins (Plakoglobin, Desmoplakin and Plakophilin), Connexin-43, and N-cadherin in Arrhythmogenic Cardiomyopathy: An Autopsy Study. Open Cardiovascular Medicine Journal 2013; 7: 28–35.

38. Kwon YS, Park TI, Cho Y, Bae MH, Kim S. Clinical usefulness of immunohistochemistry for plakoglobin, N-cadherin, and connexin-43 in the diagnosis of arrhythmogenic right ventricular cardiomyopathy. Int J Clin Exp Pathol 2013; 6(12): 2928-2935.

39. Romero J, Mejia-Lopez E, Manrique C, Lucariello R. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC/D): A Systematic Literature Review. Clin Med Insights Cardiol 2013; 7: 97–114.

40. Groeneweg JA, van der Heijden JF, Dooijes van Veen TAB, van Tintelen JP, Hauer RN. Arrhythmogenic cardiomyopathy: diagnosis, genetic background, and risk management. Neth Heart J 2014; 22(7-8): 316–325.

41. Gerlis LM, Schmidt-Ott SC, Ho SY, Anderson RH. Dysplastic conditions of the right ventricular myocardium: Uhl’s anomaly vs arrhythmogenic right ventricular dysplasia. British Heart Journal 1993; 69(2): 142-150.

42. Schejbal V. Epicardial fatty tissue of the right ventricle – morphology, morphometry and functional significance. Pneumologie 1989; 43: 490-499.

43. Beffagna G, Occhi G, Nava A, et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res 2005; 65(2): 366–373.

44. Merner ND, Hodgkinson KA, Haywood AF, et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am J Hum Genet 2008; 82(4): 809–821.

45. Van Tintelen JP, Van Gelder IC, Asimaki A, et al. Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene. Heart Rhythm 2009; 6(11): 1574–1583.

46. Taylor M, Graw S, Sinagra G, et al. Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes. Circulation 2011; 124(8): 876–885.

47. Quarta G, Syrris P, Ashworth M, et al. Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2012; 33(9): 1128–1136.

48. Van Hengel J, Calore M, Bauce B, et al. Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2013; 34(3): 201–210.

49. Van der Zwaag PA, van Rijsingen IA, Asimaki A, 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(11): 1199–1207.

50. McNally E, MacLeod H, Dellefave-Castillo L. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. 2005 Apr 18 [Updated 2014 Jan 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1131/

51. Rigato I, Corrado D, Basso C. Pharmacotherapy and other therapeutic modalities for managing arrhythmogenic right ventricular cardiomyopathy. Cardiovasc Drugs Ther 2015; 29: 171–177.

52. Mavroidis M, Davos C H, Psarras S. Complement system modulation as a target for treatment of arrhythmogenic cardiomyopathy. Basic Res Cardiol 2015; 110(3): 27.

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