Outcomes in Dutch DPP6 risk haplotype for familial idiopathic ventricular fibrillation: a focused update

Auke T. J. Bergeman, Wiert F. N. Hoeksema, Martijn H. van der Ree, Lucas V. A. Boersma, Sing-Chien Yap, Lisa M. G. Verheul, Rutger J. Hassink, Saskia N. van der Crabben, Paul G. A. Volders, Christian van der Werf, Arthur A. M. G. Wilde, Pieter G. Postema*, European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BackgroundThe genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown.MethodsDPP6 risk haplotype-positive family members (DPP6 cases) 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.ResultsWe included 327 DPP6 cases and 315 DPP6 controls. Median follow-up time was 9 years (interquartile range: 4-12). Of the DPP6 cases, 129 (39%) reached the composite endpoint of appropriate ICD shock, sudden cardiac arrest or death, at a median age of 45 years (range: 15-97). Median overall survival was 83 years and 87 years for DPP6 cases and DPP6 controls, respectively (p < 0.001). In DPP6 cases, median overall survival was shorter for males (74 years) than females (85 years) (p < 0.001). Of the DPP6 cases, 97 (30%) died, at a median age of 50 years. With a prophylactic ICD implantation advise based on risk haplotype, sex and age, 137 (42%) of DPP6 cases received an ICD, for primary prevention (n = 109) or secondary prevention (n = 28). In the primary prevention subgroup, 10 patients experienced a total of 34 appropriate ICD shocks, and there were no deaths during follow-up. DPP6 cases with a secondary prevention ICD experienced a total of 231 appropriate ICD shocks.ConclusionPatients with the DPP6 risk haplotype, particularly males, are at an increased risk of IVF and sudden cardiac death. Using a risk stratification approach based on risk haplotype, sex and age, a substantial proportion of patients with a primary prevention ICD experienced appropriate ICD shocks, showing the benefit of prophylactic ICD implantation with this strategy.
Original languageEnglish
Pages (from-to)309-314
Number of pages6
JournalNetherlands Heart Journal
Volume31
Issue number7-8
Early online date1 Jul 2023
DOIs
Publication statusPublished - Aug 2023

Keywords

  • Sudden cardiac death
  • Idiopathic ventricular fibrillation
  • DPP6
  • FOUNDER MUTATIONS
  • CARDIAC-ARREST
  • PREVALENCE

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