title: Risk stratification in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers.
abstract: BACKGROUND
  We investigated the role of phenotypic characteristics in stratifying the risk of sustained ventricular arrhythmias in patients harboring arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutations.
  
  
  RESULTS
  Clinical, electrocardiographic, and arrhythmic outcome (composite measure of first occurrence of sustained ventricular tachycardia/resuscitated sudden cardiac death/sudden cardiac death/appropriate implantable cardioverter-defibrillator therapy) data were obtained for 215 patients (104 families; 85% PKP-2). During a mean follow-up of 7 years, 86 (40%) patients experienced the arrhythmic outcome. Event-free survival was significantly lower among probands (P<0.001) and symptomatic (P<0.001) patients. Integration of ECG repolarization and depolarization abnormalities allowed for differential risk categorization. Event-free survival at 5 years for the low-risk ECG group (0-1 T inversions or minor depolarization changes) was 97% versus 81% for the intermediate-risk ECG group (2 T inversions+minor depolarization changes) versus 33% for the high-risk ECG group (≥3 T inversions±major or minor depolarization changes; P<0.001). Incremental arrhythmic risk was seen in patients with increasing premature ventricular complex count on a Holter (P<0.001). Proband status (hazard ratio, 7.7; 95% confidence interval, 2.8-22.5; P<0.001), ≥3 T-wave inversions (hazard ratio, 4.2; 95% confidence interval, 1.2-14.5; P=0.035), and male sex (hazard ratio, 1.8; 95% confidence interval, 1.2-2.8; P=0.004) were independent predictors of the first arrhythmic event on multivariable analysis.
  
  
  CONCLUSIONS
  Pedigree evaluation, an ECG, and a Holter examination provide for comprehensive arrhythmic risk stratification in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutations. We propose an approach to risk stratification based on these variables.
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bhonsale
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Madhavan
authors.forename: Binu
authors.initials: B
authors.lastname: Philips
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.forename: Theodore
authors.initials: T
authors.lastname: Abraham
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
mesh_terms: D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D016001:Confidence Intervals; D017147:Defibrillators, Implantable; D004562:Electrocardiography / Q000379:methods; D015716:Electrocardiography, Ambulatory / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D016019:Survival Analysis; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*
keywords: cardiomyopathies; electrocardiography; risk factors; survival; tachycardia