Arrhythmogenic Right Ventricular Cardiomyopathy: Risk Stratification and Indications for Defibrillator Therapy

Current Cardiology Reports

Volumn 18, Issue 6, 2016, Pages

  Zorzi, Alessandro ^a   Rigato, Ilaria ^a   Bauce, Barbara ^a   Pilichou, Kalliopi ^a   Basso, Cristina ^a   Thiene, Gaetano ^a   Iliceto, Sabino ^a   Corrado, Domenico ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Guidelines; Implantable cardioverter defibrillator; Sudden cardiac death; Ventricular arrhythmias; Ventricular fibrillation; Ventricular tachycardia

Indexed keywords

CLINICAL FEATURE; DEFIBRILLATION; ELECTROCARDIOGRAM; GENE MUTATION; GENOTYPE; HEART ARREST; HEART ARRHYTHMIA; HEART ELECTROPHYSIOLOGY; HEART PACING; HEART RIGHT VENTRICLE DYSPLASIA; HEART VENTRICLE ARRHYTHMIA; HEART VENTRICLE FIBRILLATION; HUMAN; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; MOLECULAR GENETICS; MULTICENTER STUDY (TOPIC); PROGNOSIS; REVIEW; RISK FACTOR; RISK MANAGEMENT; SUDDEN CARDIAC DEATH; TREATMENT INDICATION; ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA; COMPLICATION; DEATH, SUDDEN, CARDIAC; PATHOPHYSIOLOGY; RISK ASSESSMENT; SURVIVAL ANALYSIS;

ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA; DEATH, SUDDEN, CARDIAC; DEFIBRILLATORS, IMPLANTABLE; HUMANS; RISK ASSESSMENT; RISK FACTORS; SURVIVAL ANALYSIS;

EID: 84964955525     PISSN: 15233782     EISSN: 15343170     Source Type: Journal    
DOI: 10.1007/s11886-016-0734-9     Document Type: Review

References (64)

1. Basso C, Corrado D, Marcus F, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. Lancet. 2009;373:1289–300.
2. Corrado D, Basso C, Thiene G, et al. Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study. J Am Coll Cardiol. 1997;30:1512–20.
3. Basso C, Thiene G, Corrado D, Angelini A, Nava A, Valente M. Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation. 1996;94:983–91.
4. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, Malergue C, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation. 1982;65:384–98.
5. Rigato I, Bauce B, Rampazzo A, 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.
6. Basso C, Bauce B, Corrado D, Thiene G. Pathophysiology of arrhythmogenic cardiomyopathy. Nat Rev Cardiol. 2012;9:223–33.
7. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol. 2003;42:1959–63.
8. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med. 1988;318:129–33.
9. Migliore F, Zorzi A, Silvano M, Rigato I, Basso C, Thiene G, et al. Clinical management of arrhythmogenic right ventricular cardiomyopathy: an update. Curr Pharm Des. 2010;16:2918–28.
10. Thiene G, Corrado D, Nava A, Rossi L, Poletti A, Boffa GM, et al. Right ventricular cardiomyopathy: is there evidence of an inflammatory aetiology? Eur Heart J. 1991;12:22–5.
11. Patrianakos AP, Protonotarios N, Nyktari E, Pagonidis K, Tsatsopoulou A, Parthenakis FI, et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia and troponin release. Myocarditis or the “hot phase” of the disease? Int J Cardiol. 2012;157:e26–8.
12. Cerrone M, Lin X, Zhang M, et al. Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype. Circulation. 2014;129:1092–103.
13. Delmar M, Liang FX. Connexin43 and the regulation of intercalated disc function. Heart Rhythm. 2012;9:835–8.
14. 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;33:1942–53.
15. Rizzo S, Lodder EM, Verkerk AO, Wolswinkel R, Beekman L, Pilichou K, et al. Intercalated disc abnormalities, reduced Na(+) current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes. Cardiovasc Res. 2012;95:409–18.
16. Sato PY, Musa H, Coombs W, Guerrero-Serna G, Patino GA, Taffet SM, et al. Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res. 2009;105:523–6.
17. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, 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;71:215–8.
18. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010;121:1533–41.
19. Sen-Chowdhry S, Syrris P, Prasad SK, Hughes SE, Merrifield R, Ward D, et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol. 2008;52:2175–87.
20. Corrado D, Leoni L, Link MS, et al. Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation. 2003;108:3084–91.
21. Wichter T, Paul M, Wollmann C, et al. Implantable cardioverter/defibrillator therapy in arrhythmogenic right ventricular cardiomyopathy: single-center experience of long-term follow-up and complications in 60 patients. Circulation. 2004;109:1503–8.
22. Roguin A, Bomma CS, Nasir K, et al. Implantable cardioverter-defibrillators in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2004;43:1843–52.
23. Corrado D, Calkins H, Link MS, et al. Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia. Circulation. 2010;122:1144–52.
24. Bhonsale A, James CA, Tichnell C, 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;58:1485–96.
25. Blomstrom-Lundqvist C, Sabel KG, Olsson SB. A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia. Br Heart J. 1987;58:477–88.
26. Marcus FI, Fontaine GH, Frank R, Gallagher JJ, Reiter MJ. Long-term follow-up in patients with arrhythmogenic right ventricular disease. Eur Heart J. 1989;10(Suppl D):68–73.
27. Hulot JS, Jouven X, Empana JP, Frank R, Fontaine G. Natural history and risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2004;110:1879–84.
28. Lemola K, Brunckhorst C, Helfenstein U, Oechslin E, Jenni R, Duru F. Predictors of adverse outcome in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy: long term experience of a tertiary care centre. Heart. 2005;91:1167–72.
29. Peters S. Long-term follow-up and risk assessment of arrhythmogenic right ventricular dysplasia/cardiomyopathy: personal experience from different primary and tertiary centres. J Cardiovasc Med (Hagerstown). 2007;8:521–6.
30. Watkins DA, Hendricks N, Shaboodien G, et al. Clinical features, survival experience, and profile of plakophylin-2 gene mutations in participants of the arrhythmogenic right ventricular cardiomyopathy registry of South Africa. Heart Rhythm. 2009;6:S10–7.
31. Pinamonti B, Dragos AM, Pyxaras SA, Merlo M, Pivetta A, Barbati G, et al. Prognostic predictors in arrhythmogenic right ventricular cardiomyopathy: results from a 10-year registry. Eur Heart J. 2011;32:1105–13.
32. Bhonsale A, James CA, Tichnell C, Murray B, Madhavan S, Philips B, et al. Risk stratification in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. Circ Arrhythm Electrophysiol. 2013;6:569–78.
33. Saguner AM, Ganahl S, Baldinger SH, et al. Usefulness of electrocardiographic parameters for risk prediction in arrhythmogenic right ventricular dysplasia. Am J Cardiol. 2014;113:1728–34.
34. Saguner AM, Vecchiati A, Baldinger SH, et al. Different prognostic value of functional right ventricular parameters in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circ Cardiovasc Imaging. 2014;7:230–9.
35. Zorzi A, Migliore F, Elmaghawry M, et al. Electrocardiographic predictors of electroanatomic scar size in arrhythmogenic right ventricular cardiomyopathy: implications for arrhythmic risk stratification. J Cardiovasc Electrophysiol. 2013;24:1321–7.
36. Tschabrunn CM, Marchlinski FE. Ventricular tachycardia mapping and ablation in arrhythmogenic right ventricular cardiomyopathy/dysplasia: lessons learned. World J Cardiol. 2014;6:959–67.
37. Link MS, Laidlaw D, Polonsky B, Zareba W, McNitt S, Gear K, et al. Ventricular arrhythmias in the North American multidisciplinary study of ARVC: predictors, characteristics, and treatment. J Am Coll Cardiol. 2014;64:119–25. The North American multidisciplinary study on ARVC patients failed to demonstrate that inducible ventricular tachycardia at programmed ventricular stimulation is independently associated with arrhythmic events during follow-up.
38. Saguner AM, Medeiros-Domingo A, Schwyzer MA, et al. Usefulness of inducible ventricular tachycardia to predict long-term adverse outcomes in arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol. 2013;111:250–7.
39. Corrado D, Basso C, Leoni L, et al. Three-dimensional electroanatomic voltage mapping increases accuracy of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation. 2005;111:3042–50.
40. Corrado D, Basso C, Leoni L, et al. Three-dimensional electroanatomical voltage mapping and histologic evaluation of myocardial substrate in right ventricular outflow tract tachycardia. J Am Coll Cardiol. 2008;51:731–9.
41. Migliore F, Zorzi A, Silvano M, et al. Prognostic value of endocardial voltage mapping in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circ Arrhythm Electrophysiol. 2013;6:167–76. The study evaluated the presence and degree of fibro-fatty myocardial scar with invasive endocardial voltage mapping and demonstrated a correlation between scar extent and arrhythmic risk, supporting the phenotype-based risk stratification strategy.
42. Santangeli P, Dello Russo A, Pieroni M, et al. Fragmented and delayed electrograms within fibrofatty scar predict arrhythmic events in arrhythmogenic right ventricular cardiomyopathy: results from a prospective risk stratification study. Heart Rhythm. 2012;9:1200–6.
43. Cox MG, van der Zwaag PA, van der Werf C, 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;123:2690–700.
44. Dalal D, Molin LH, Piccini J, et al. Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation. 2006;113:1641–9.
45. Nava A, Bauce B, Basso C, Muriago M, Rampazzo A, Villanova C, et al. Clinical profile and long-term follow-up of 37 families with arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2000;36:2226–33.
46. Bauce B, Frigo G, Marcus FI, et al. Comparison of clinical features of arrhythmogenic right ventricular cardiomyopathy in men versus women. Am J Cardiol. 2008;102:1252–7.
47. Protonotarios A, Anastasakis A, Panagiotakos DB, Antoniades L, Syrris P, Vouliotis A, et al. Arrhythmic risk assessment in genotyped families with arrhythmogenic right ventricular cardiomyopathy. Europace. 2015.
48. Patten RD, Pourati I, Aronovitz MJ, et al. 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res. 2004;95:692–9.
49. Valente M, Calabrese F, Thiene G, Angelini A, Basso C, Nava A, et al. In vivo evidence of apoptosis in arrhythmogenic right ventricular cardiomyopathy. Am J Pathol. 1998;152:479–84.
50. 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.
51. 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;12:861–8.
52. Bauce B, Nava A, Beffagna G, et al. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm. 2010;7:22–9.
53. Xu T, Yang Z, Vatta M, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2010;55:587–97.
54. Kaplan SR, Gard JJ, Protonotarios N, et al. Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease). Heart Rhythm. 2004;1:3–11.
55. Zorzi A, Rigato I, Pilichou K, et al. Phenotypic expression is a prerequisite for malignant arrhythmic events and sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy. Europace. 2015; in press. The study investigated the arrhythmic risk of desmosomal gene mutations carriers, comparing those with overt ARVC with those with no or mild phenotypic expression.
56. Te Riele AS, James CA, Groeneweg JA, et al. Approach to family screening in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Eur Heart J. 2015. The study from the John Hopkins group confirmed that family members of arrhythmogenic cardiomyopathy show a low risk of events until the disease becomes overt.
57. te Riele AS, Bhonsale A, James CA, et al. Incremental value of cardiac magnetic resonance imaging in arrhythmic risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol. 2013;62:1761–9.
58. Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary. Heart Rhythm. 2008;5:934–55.
59. Priori SG, Blomstrom-Lundqvist C, Mazzanti A, 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). Europace. 2015;17(11):1601–87. The European Heart Association guidelines on ventricular arrhythmias and prevention of sudden cardiac death specifically address indications to ICD implantation in arrhythmogenic cardiomyopathy.
60. Corrado D, Wichter T, Link MS, et al. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement. Eur Heart J. 2015;36(46):3227–37. This is a consensus document from many experts from both Europe and US specifically addressing the treatment of ARVC.
61. Kirchhof P, Fabritz L, Zwiener M, et al. Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation. 2006;114:1799–806.
62. 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. The study demonstrated that a history of competitive sports activity is associated with increased disease penetrance and higher risk of ventricular arrhythmias in desmosomal-gene mutation carriers.
63. Saberniak J, Hasselberg NE, Borgquist R, Platonov PG, Sarvari SI, Smith HJ, et al. Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members. Eur J Heart Fail. 2014;16:1337–44.
64. Corrado D, Zorzi A. Arrhythmogenic right ventricular cardiomyopathy and sports activity. Eur Heart J. 2015;36:1708–10.