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. 2023 Aug;31(7-8):309-314.
doi: 10.1007/s12471-023-01792-1. Epub 2023 Jul 27.

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

Auke T Bergeman  1   2 , Wiert F Hoeksema  1   2 , Martijn H van der Ree  1   2 , Lucas V A Boersma  3 , Sing-Chien Yap  4 , Lisa M Verheul  5 , Rutger J Hassink  5 , Saskia N van der Crabben  6 , Paul G A Volders  7 , Christian van der Werf  1   2 , Arthur A M Wilde  1   2 , Pieter G Postema  8   9 ; European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart
Collaborators, Affiliations

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

Auke T Bergeman et al. Neth Heart J. 2023 Aug.

Abstract

Background: The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown.

Methods: DPP6 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.

Results: We 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.

Conclusion: Patients 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.

Keywords: DPP6; Idiopathic ventricular fibrillation; Sudden cardiac death.

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Conflict of interest statement

A.T. Bergeman, W.F. Hoeksema, M.H. van der Ree, L.M. Verheul, R.J. Hassink, S.N. van der Crabben, P.G. A. Volders, C. van der Werf, A.A. M. Wilde and P.G. Postema declare that they have no competing interests. S.-C. Yap has received a research grant from Medtronic and Biotronik and consulting fees from Boston Scientific. P. G. A. Boersma is consultant for Medtronic, Boston Scientific and Adagio.

Figures

Fig. 1
Fig. 1
Survival curves showing mortality in DPP6 cases and DPP6 controls
Fig. 2
Fig. 2
Survival curves showing mortality in male and female DPP6 cases
Fig. 3
Fig. 3
Survival curve showing mortality, aborted sudden cardiac arrest or first appropriate implantable cardioverter-defibrillator (ICD) shock in all DPP6 cases
See this image and copyright information in PMC

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