The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overview.

Autor:	Verheul LM; Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands., van der Ree MH; Department of Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.; Heart Failure and Arrhythmias, Amsterdam, Cardiovascular Sciences, Amsterdam, The Netherlands., Groeneveld SA; Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands., Mulder BA; Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands., Christiaans I; Department of Human Genetics, University Medical Center Groningen, Groningen, The Netherlands., Kapel GFL; Department of Cardiology, Medisch Spectrum Twente, Enschede, The Netherlands., Alings M; Department of Cardiology, Amphia Hospital, Breda, The Netherlands., Bootsma M; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands., Barge-Schaapveld DQCM; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Balt JC; Department of Cardiology, St.Antonius Hospital, Nieuwegein, The Netherlands., Yap SC; Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands., Krapels IPC; Department of Human Genetics, Maastricht University Medical Center+, Maastricht, The Netherlands., Ter Bekke RMA; Department of Cardiology, Maastricht University Medical Center+, Maastricht, The Netherlands., Volders PGA; Department of Cardiology, Maastricht University Medical Center+, Maastricht, The Netherlands., van der Crabben SN; Department of Human Genetics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Postema PG; Department of Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.; Heart Failure and Arrhythmias, Amsterdam, Cardiovascular Sciences, Amsterdam, The Netherlands., Wilde AAM; Department of Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.; Heart Failure and Arrhythmias, Amsterdam, Cardiovascular Sciences, Amsterdam, The Netherlands., Dooijes D; Department of Human Genetics, University Medical Center Utrecht, Utrecht, The Netherlands., Baas AF; Department of Human Genetics, University Medical Center Utrecht, Utrecht, The Netherlands., Hassink RJ; Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands.
Jazyk:	angličtina
Zdroj:	Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology [Europace] 2023 Nov 02; Vol. 25 (11).
DOI:	10.1093/europace/euad336
Abstrakt:	Aims: During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. Methods and Results: We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27-51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC, MYL2, MYH7, PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1, SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P < 0.001). Conclusion: Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed. Competing Interests: Conflict of interest: P.G.P. is an associate editor of Europace and was not involved in the peer review process or publication decision. S.-C.Y. is a consultant for Boston Scientific and has received lecture fees and research grants from Medtronic, Biotronik, and Boston Scientific. All remaining authors have declared no conflicts of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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