title: The impact of implantable cardioverter-defibrillator therapy on survival in autosomal-dominant arrhythmogenic right ventricular cardiomyopathy (ARVD5).
abstract: OBJECTIVE
  We sought to determine the impact of implantable cardioverter-defibrillator (ICD) therapy in patients with familial arrhythmogenic right ventricular cardiomyopathy (ARVC).
  
  
  BACKGROUND
  Arrhythmogenic right ventricular cardiomyopathy is a cause of sudden cardiac death, which may be prevented by ICD.
  
  
  METHODS
  We studied 11 families in which a 3p25 deoxyribonucleic acid (DNA) haplotype at locus ARVD5 segregated with disease and compared mortality in subjects who received an ICD with that in control subjects who were matched for age, gender, ARVC status, and family. Subjects (n = 367) at 50% a priori risk of inheriting ARVC were classified as high risk (HR) (n = 197), low risk (n = 92), or unknown (n = 78) on the basis of clinical events, DNA haplotyping, and/or pedigree position. Forty-eight HR subjects (30 males, [median age 32 years] and 18 females [median age 41 years]) were followed after ICD (secondary to ventricular tachycardia [VT] in 27%). Survival was compared with 58 HR control subjects who were alive at the same age to-the-day at which the ICD subject received the device.
  
  
  RESULTS
  In the HR group, 50% of males were dead by 39 years and females by 71 years: relative risk of death was 5.1 (95% confidence interval 3 to 8.5) for males. The five-year mortality rate after ICD in males was zero compared with 28% in control subjects (p = 0.009). Within five years, the ICD fired for VT in 70% and for VT >240 beats/min in 30%, with no difference in discharge rate when analyzed by ICD indication.
  
  
  CONCLUSIONS
  The unknown mutation at the ARVD5 locus causing ARVC results in high mortality. Risk stratification using genetic haplotyping and ICD therapy produced improved survival for males.
authors.affiliation: Clinical Epidemiology Unit, Memorial University Health Sciences Centre, St. John's, Newfoundland, Canada A1B 3V6.
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Hodgkinson
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.forename: Anne S
authors.initials: AS
authors.lastname: Bassett
authors.forename: Christine
authors.initials: C
authors.lastname: Kupprion
authors.forename: Jörg
authors.initials: J
authors.lastname: Drenckhahn
authors.forename: Mark W
authors.initials: MW
authors.lastname: Norman
authors.forename: Ludwig
authors.initials: L
authors.lastname: Thierfelder
authors.forename: Susan N
authors.initials: SN
authors.lastname: Stuckless
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Dicks
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Sean P
authors.initials: SP
authors.lastname: Connors
mesh_terms: D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome