Outcomes in Dutch DPP6 risk haplotype for familial idiopathic ventricular fibrillation: afocused update.

Abstract

The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown. DPP6 risk haplotype-positive family members (DPP6cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023. Implantable cardioverter-defibrillator (ICD) indication was divided in primary or secondary prevention. Cumulative survival and event rates were calculated. We included 327 DPP6cases and 315 DPP6 controls. Median follow-up time was 9years (interquartile range: 4-12). Of the DPP6cases, 129 (39%) reached the composite endpoint of appropriate ICD shock, sudden cardiac arrest or death, at amedian age of 45years (range: 15-97). Median overall survival was 83years and 87years for DPP6cases and DPP6 controls, respectively (p < 0.001). In DPP6cases, median overall survival was shorter for males (74years) than females (85years) (p < 0.001). Of the DPP6cases, 97 (30%) died, at amedian age of 50years. With aprophylactic ICD implantation advise based on risk haplotype, sex and age, 137 (42%) of DPP6cases received an ICD, for primary prevention (n = 109) or secondary prevention (n = 28). In the primary prevention subgroup, 10patients experienced atotal of 34 appropriate ICD shocks, and there were no deaths during follow-up. DPP6cases with asecondary prevention ICD experienced atotal of 231 appropriate ICD shocks. Patients with the DPP6 risk haplotype, particularly males, are at an increased risk of IVF and sudden cardiac death. Using arisk stratification approach based on risk haplotype, sex and age, asubstantial proportion of patients with aprimary prevention ICD experienced appropriate ICD shocks, showing the benefit of prophylactic ICD implantation with this strategy.