title: Arrhythmogenic right ventricular cardiomyopathy/dysplasia on the basis of the revised diagnostic criteria in affected families with desmosomal mutations.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Yannis Protonotarios Medical Centre, Hora Naxos, Naxos, Greece. nikos.protonotarios@otenet.gr
authors.forename: Nikos
authors.initials: N
authors.lastname: Protonotarios
authors.forename: Aris
authors.initials: A
authors.lastname: Anastasakis
authors.forename: Loizos
authors.initials: L
authors.lastname: Antoniades
authors.forename: Gregory
authors.initials: G
authors.lastname: Chlouverakis
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.forename: Cristina
authors.initials: C
authors.lastname: Basso
authors.forename: Angeliki
authors.initials: A
authors.lastname: Asimaki
authors.forename: Artemisia
authors.initials: A
authors.lastname: Theopistou
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Adalena
authors.initials: A
authors.lastname: Tsatsopoulou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000235:genetics; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics*; D003896:Desmosomes / Q000235:genetics*; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011446:Prospective Studies; D055815:Young Adult