Marloes Visser1, Dennis Dooijes2, Jasper J van der Smagt2, Jeroen F van der Heijden3, Pieter A Doevendans3, Peter Loh3, Folkert W Asselbergs3, Rutger J Hassink4. 1. Department of Cardiology, University Medical Centre, Utrecht, The Netherlands; Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, The Netherlands,. Electronic address: m.visser-14@umcutrecht.nl. 2. Department of Clinical Genetics, University Medical Centre, Utrecht, The Netherlands. 3. Department of Cardiology, University Medical Centre, Utrecht, The Netherlands. 4. Department of Cardiology, University Medical Centre, Utrecht, The Netherlands; Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, The Netherlands.
Abstract
BACKGROUND: Idiopathic ventricular fibrillation (IVF) is a rare primary cardiac arrhythmia syndrome that is diagnosed in a resuscitated cardiac arrest victim, with documented ventricular fibrillation, in whom no underlying cause is identified after comprehensive clinical evaluation. In some patients, causative genetic mutations are detected that facilitate patient treatment and follow-up. The feasibility of next-generation sequencing (NGS) has increased with its greater availability and decreasing costs. OBJECTIVE: The aim of this study was to assess the diagnostic yield of NGS in patients with IVF. METHODS: A total of 33 patients initially diagnosed with IVF were included (mean age 53 ± 15 years; 14(42%) men). In all included patients, NGS of 33 genes and the DPP6 haplotype revealed no pathogenic mutations. Genetic screening comprised NGS of a panel of 179 additional genes. Variants with a minor allele frequency of <0.05% were assessed for pathogenicity by using existing mutation databases and in silico predictive algorithms. RESULTS: In 1 of 33 patients, a likely pathogenic mutation was detected. The added yield of genetic testing with NGS of 179 additional genes is 3% in patients with IVF. In 15% of patients, 1 or multiple variants of uncertain clinical significance were detected. CONCLUSION: The added yield of genetic screening of extended NGS panels in patients initially diagnosed with IVF is minimal. Routine analysis of large diagnostic NGS panels is therefore not recommended.
BACKGROUND:Idiopathic ventricular fibrillation (IVF) is a rare primary cardiac arrhythmia syndrome that is diagnosed in a resuscitated cardiac arrest victim, with documented ventricular fibrillation, in whom no underlying cause is identified after comprehensive clinical evaluation. In some patients, causative genetic mutations are detected that facilitate patient treatment and follow-up. The feasibility of next-generation sequencing (NGS) has increased with its greater availability and decreasing costs. OBJECTIVE: The aim of this study was to assess the diagnostic yield of NGS in patients with IVF. METHODS: A total of 33 patients initially diagnosed with IVF were included (mean age 53 ± 15 years; 14(42%) men). In all included patients, NGS of 33 genes and the DPP6 haplotype revealed no pathogenic mutations. Genetic screening comprised NGS of a panel of 179 additional genes. Variants with a minor allele frequency of <0.05% were assessed for pathogenicity by using existing mutation databases and in silico predictive algorithms. RESULTS: In 1 of 33 patients, a likely pathogenic mutation was detected. The added yield of genetic testing with NGS of 179 additional genes is 3% in patients with IVF. In 15% of patients, 1 or multiple variants of uncertain clinical significance were detected. CONCLUSION: The added yield of genetic screening of extended NGS panels in patients initially diagnosed with IVF is minimal. Routine analysis of large diagnostic NGS panels is therefore not recommended.
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Back Sternick Eduardo; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong-Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti Mac Intyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Pablo Ochoa Juan; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: J Arrhythm Date: 2022-05-31
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Eduardo Back Sternick; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti MacIntyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Juan Pablo Ochoa; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: Europace Date: 2022-09-01 Impact factor: 5.486
Authors: Martin K Stiles; Arthur A M Wilde; Dominic J Abrams; Michael J Ackerman; Christine M Albert; Elijah R Behr; Sumeet S Chugh; Martina C Cornel; Karen Gardner; Jodie Ingles; Cynthia A James; Jyh-Ming Jimmy Juang; Stefan Kääb; Elizabeth S Kaufman; Andrew D Krahn; Steven A Lubitz; Heather MacLeod; Carlos A Morillo; Koonlawee Nademanee; Vincent Probst; Elizabeth V Saarel; Luciana Sacilotto; Christopher Semsarian; Mary N Sheppard; Wataru Shimizu; Jonathan R Skinner; Jacob Tfelt-Hansen; Dao Wu Wang Journal: Heart Rhythm Date: 2020-10-19 Impact factor: 6.343
Authors: Martin K Stiles; Arthur A M Wilde; Dominic J Abrams; Michael J Ackerman; Christine M Albert; Elijah R Behr; Sumeet S Chugh; Martina C Cornel; Karen Gardner; Jodie Ingles; Cynthia A James; Jyh-Ming Jimmy Juang; Stefan Kääb; Elizabeth S Kaufman; Andrew D Krahn; Steven A Lubitz; Heather MacLeod; Carlos A Morillo; Koonlawee Nademanee; Vincent Probst; Elizabeth V Saarel; Luciana Sacilotto; Christopher Semsarian; Mary N Sheppard; Wataru Shimizu; Jonathan R Skinner; Jacob Tfelt-Hansen; Dao Wu Wang Journal: J Arrhythm Date: 2021-04-08
Authors: Giulio Conte; Bernard Belhassen; Pier Lambiase; Giuseppe Ciconte; Carlo de Asmundis; Elena Arbelo; Beat Schaer; Antonio Frontera; Haran Burri; Leonardo Calo'; Kostantinos P Letsas; Francisco Leyva; Bradley Porter; Johan Saenen; Valerio Zacà; Paola Berne; Peter Ammann; Marco Zardini; Blerim Luani; Roberto Rordorf; Georgia Sarquella Brugada; Argelia Medeiros-Domingo; Johann-Christoph Geller; Tom de Potter; Mathis K Stokke; Manlio F Márquez; Yoav Michowitz; Shohreh Honarbakhsh; Manuel Conti; Christian Sticherling; Annamaria Martino; Abbasin Zegard; Tardu Özkartal; Maria Luce Caputo; François Regoli; Rüdiger C Braun-Dullaeus; Francesca Notarangelo; Tiziano Moccetti; Gavino Casu; Christopher A Rinaldi; Moises Levinstein; Kristina H Haugaa; Nicolas Derval; Catherine Klersy; Moreno Curti; Carlo Pappone; Hein Heidbuchel; Josép Brugada; Michel Haïssaguerre; Pedro Brugada; Angelo Auricchio Journal: Europace Date: 2019-11-01 Impact factor: 5.214