Abstract 13095: Phenotype, Genotype and Natural History of Arrhythmogenic Dilated Cardiomyopathy
Background: Arrhythmogenic dilated cardiomyopathy (aDCM) is a form of dilated cardiomyopathy (DCM) frequently encountered in clinical practice and characterized by severe ventricular arrhythmias. The purpose of this study was to determine the prevalence, genotype-phenotype correlations and long-term outcome predictors of aDCM, to implement current criteria for risk-stratification.
METHODS: From February 1979 to November 2012, we studied a 461 patients (364 families) with DCM enrolled in the Familial Cardiomyopathy Registry. Criteria for aDCM were DCM with VT, SD, AICD shock, syncope, cardiac arrest, PVC>1000/24h. A subgroup of patients was tested for DCM genes (MYH6, MYH7, MYBPC3, TNNT2, TTN, LMNA, LAP2, SCN5A, DES). For survival analysis, endpoints were: 1) death or heart transplant, 2) death, heart transplant or malignant ventricular arrhythmias (MVA), 3) MVA.
RESULTS: Over a follow-up of 96±82 months (up to 20 years), we identified 211 patients (45.8%) with aDCM: among them 72 (15.6% of the total DCM population) experienced MVA during follow-up. When compared to DCM patients, aDCM patients had worse survival (endpoint 1: P=0.006; endpoint 2: P<0.001). Independent risk factors for endpoint 1 in the aDCM population were LVEF<34% and the presence of QRS>110 ms in V1-V3. There was a cumulative risk for death or heart transplant per additional risk factor. Predictors of MVA in the aDCM population were the presence of QRS>110 ms in V1-V3 and family history of MVA. aDCM was most frequent among LMNA (70.6%), TTN (54.5%) and SCN5A variant carriers (50%). Furthermore, nuclear envelope (LMNA and LAP2) variant carriers had worse NYHA (P=0.030) in spite of smaller LVEDD at baseline (P=0.003), and experienced more heart transplants (P=0.010). TTN carriers had worse event-free survival for endpoint 2 (P=0.037). Finally, SCN5A mutation carriers were younger at enrollment (P=0.004) compared to non-carriers, had prevalence of males (P=0.029) and epsilon waves (P=0.030).
CONCLUSIONS: In a large and extensively studied DCM cohort, we define a novel subpopulation characterized by prominent ventricular arrhythmia and different prognosis. Our results suggest that aDCM may benefit from more aggressive therapeutic interventions including modified ICD criteria.
- © 2013 by American Heart Association, Inc.