Detailed characterization of familial idiopathic ventricular fibrillation linked to the DPP6 locus

Background Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and is notoriously difficult to manage because 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 The purpose of this study was to expand our knowledge of familial IVF and to 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 magnetic resonance documented slightly larger ventricular volumes in haplotype-positives compared to controls (P <.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 ventricular fibrillation (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 <.01), with a worse phenotype in males (median survival 63 vs 83 years in females, P <.01). Implantable cardioverter-defibrillators were implanted in 99 patients (76 [77%] for primary prevention). Two arrhythmic events occurred in the primary prevention group during follow-up (5 ± 3 years). Conclusion Despite our extensive analysis, the complexity in identifying asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.

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