Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus

BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and notoriously difficult to manage as there are no clinical risk indicators for premature cardiac arrest. Previously, we identified a link between familial-IVF and a risk-haplotype on chromosome 7q36 (involving the arrhythmia gene DPP6). OBJECTIVE: To expand our knowledge of familial-IVF and discuss its (extended) clinical characteristics. METHODS: We studied 601 family members and probands; 286 DPP6 risk-haplotype positive (haplotype-positive) and 315 DPP6 risk-haplotype negative (haplotype-negative) individuals. Clinical parameters, a combination of all-cause mortality and (aborted) cardiac arrest and differences between haplotype-positives and haplotype-negatives were evaluated. RESULTS: There were no differences in electrocardiographic indices between haplotype-positives and haplotype-negatives, or between haplotype-positives with or without events. Cardiac MR documented slightly larger ventricular volumes in haplotype-positives compared to controls (p<0.05) but these were not clinically useful. Mortality and/or cardiac arrest occurred in 85 haplotype-positives (30%) and 18 haplotype-negatives (6%). Twenty-four haplotype-positives(8%, male) were resuscitated from VF. Documented VF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall. Median survival in risk-haplotype haplotype-positives was 70 vs. 93 years for haplotype-negatives (p<0.01), with a worse phenotype in males (median survival 63 vs. 83 years in females, p