Arrhythmogenic right ventricular cardiomyopathy/dysplasia on the basis of the revised diagnostic criteria in affected families with desmosomal mutations

Aims To evaluate arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in affected families with desmosome mutations on the basis of the recently revised Task Force Criteria (TFC). Methods and results One hundred and three consecutive carriers of pathogenic desmosome mutations and 102 mutation-negative relatives belonging to 22 families with dominant and 14 families with recessive ARVC/D were evaluated according to the original and revised TFC. Serial cardiac assessment with 12-lead, signal-averaged, and 24 h ambulatory ECG and two-dimensional echocardiography was performed. Clinical events and outcome were prospectively analysed up to 24 years (median 4 years). With the revised criteria, 16 carriers were newly diagnosed on the basis of ECG abnormalities in 100%, ventricular arrhythmias in 79%, and functional/structural alterations in 31%, increasing diagnostic sensitivity from 57 to 71% (P = 0.001). Task Force Criteria specificity improved from 92 to 99% (P = 0.016). In dominant mutation carriers, penetrance changed significantly (61 vs. 42%, P = 0.001); no changes were observed in recessive homozygous carriers (97 vs. 97%, P = 1.00). Affected carriers according to the revised TFC (n = 73) had 12-lead ECG abnormalities in 96%, ventricular arrhythmias in 91%, and functional/structural alterations fulfilling echocardiographic criteria in 76%. Cumulative and event-free survival did not differ significantly between dominant and recessive affected carriers, being at 78.6 vs. 76 and 51.7 vs. 55.4%, respectively, by the age of 40 years. Conclusion Revised TFC increased diagnostic sensitivity particularly in dominant ARVC/D. Serial family evaluation may rely on electrocardiography which seems to have the best diagnostic utility particularly in early disease that is not detectable by two-dimensional echocardiography.

[1]  H. Calkins,et al.  Reader‐ and Instrument‐Dependent Variability in the Electrocardiographic Assessment of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy , 2011, Journal of cardiovascular electrophysiology.

[2]  Wojciech Zareba,et al.  Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: Proposed Modification of the Task Force Criteria , 2010, European heart journal.

[3]  L. Jordaens,et al.  Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Diagnostic Task Force Criteria: Impact of New Task Force Criteria , 2010, Circulation. Arrhythmia and electrophysiology.

[4]  D. Corrado,et al.  Quantitative assessment of endomyocardial biopsy in arrhythmogenic right ventricular cardiomyopathy/dysplasia: an in vitro validation of diagnostic criteria. , 2008, European heart journal.

[5]  Petros Syrris,et al.  Clinical and Genetic Characterization of Families With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Provides Novel Insights Into Patterns of Disease Expression , 2007, Circulation.

[6]  P. Syrris,et al.  Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. , 2006, American journal of human genetics.

[7]  G. Danieli,et al.  Mutations in Desmoglein-2 Gene Are Associated With Arrhythmogenic Right Ventricular Cardiomyopathy , 2006, Circulation.

[8]  G. Danieli,et al.  Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations. , 2005, European heart journal.

[9]  Walter Birchmeier,et al.  Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy , 2004, Nature Genetics.

[10]  H. Calkins,et al.  Electrocardiographic Features of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy According to Disease Severity: A Need to Broaden Diagnostic Criteria , 2004, Circulation.

[11]  G. Thiene,et al.  Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease). , 2004, Heart rhythm.

[12]  W. Mckenna,et al.  Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. , 2001, Journal of the American College of Cardiology.

[13]  A. Crosby,et al.  Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease) , 2000, The Lancet.

[14]  A. Nava,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. , 1994, British heart journal.

[15]  D. Corrado,et al.  Right ventricular cardiomyopathy and sudden death in young people. , 1988, The New England journal of medicine.

[16]  W. Mckenna,et al.  Echocardiographic measurement of the normal adult right ventricle , 1986 .

[17]  R Frank,et al.  Right Ventricular Dysplasia: A Report of 24 Adult Cases , 1982, Circulation.