Abstract 16401: Systematic Approach to Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Family Screening in a Large Transatlantic Cohort
Background: Relatives of patients with Arrhythmogenic Right Ventricular Dysplasia/ Cardiomyopathy (ARVD/C) are at increased risk of sudden death, but heterogeneous disease expression complicates their risk assessment. We sought to 1) determine predictors of manifest ARVD/C; and 2) optimize arrhythmic risk stratification in at-risk relatives.
Methods: Detailed phenotypic and outcome data of 345 relatives (46% male; 35.5 ± 18.9 years) from 140 families enrolled in the US and Dutch ARVD/C registries was obtained. Diagnosis of relatives was ascertained as per 2010 Task Force Criteria ("conventional TFC"), and according to the 2010 TFC independent of family history ("TFC independent of family history"). The primary outcome was development of sustained ventricular arrhythmia or appropriate ICD discharge in follow-up.
Results: One hundred sixteen (34%) relatives were diagnosed with ARVD/C according to conventional TFC. Multivariate analysis identified symptoms (OR 8.50 [95% CI 4.01-18.02] p<0.001) and being a sibling (OR 3.12 [95% CI 1.78-5.49] p<0.001) as strongest independent predictors of overt ARVD/C. Classification and regression tree analysis with tenfold cross-validation predicted overt disease with 78% accuracy based on symptoms (p<0.001), being a sibling (p<0.001), pathogenic mutation in the family (p<0.001) and female gender (p=0.007). During 5.9±3.9 years of follow-up, 23 (7%) relatives experienced an arrhythmic event (cycle length 269 ± 50ms). All these subjects were diagnosed on average 4.4 (IQR 1.4-7.4) years prior to the event. Since all patients with arrhythmia had both electrical and structural abnormalities, they all fulfilled TFC independent of family history. The TFC independent of family history were superior to conventional TFC in detecting cases with ventricular arrhythmia (area under the ROC curve 0.96 vs. 0.86, p<0.001).
Conclusions: One-third of at-risk relatives has overt ARVD/C. Siblings are at highest risk of disease. A combination of symptoms, being a sibling, pathogenic mutation in the family, and female gender allows for accurate prediction of overt ARVD/C. Fulfillment of TFC independent of family history is superior to conventional TFC for arrhythmic risk stratification of at-risk relatives.
Author Disclosures: A.S. te Riele: None. C.A. James: None. A.C. Sawant: None. J.A. Groeneweg: None. K. Kammers: None. B. Murray: None. C. Tichnell: None. J.F. van der Heijden: None. D.P. Judge: None. J. van Tintelen: None. R.N. Hauer: None. H. Calkins: Other Research Support; Significant; Medtronic Inc, St Jude Medical Inc. H. Tandri: None.
- © 2014 by American Heart Association, Inc.