Judith N Ten Sande1, Pieter G Postema2, S Matthijs Boekholdt1, Hanno L Tan1, Jeroen F van der Heijden3, Natasja M S de Groot4, Paul G A Volders5, Katja Zeppenfeld6, Lucas V A Boersma7, Eline A Nannenberg8, Imke Christiaans8, Arthur A M Wilde9. 1. Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 2. Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: p.g.postema@amc.uva.nl. 3. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. 4. Department of Cardiology, Erasmus Medical Center, Rotterdam, Rotterdam, The Netherlands. 5. Department of Cardiology, Maastricht University Medical Center, The Netherlands, Maastricht, The Netherlands. 6. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 7. Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands. 8. Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 9. Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia. Electronic address: a.a.wilde@amc.uva.nl.
Abstract
BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and is notoriously difficult to manage because there are no clinical risk indicators for premature cardiac arrest. Previously, we identified a link between familial IVF and a risk haplotype on chromosome 7q36 (involving the arrhythmia gene DPP6). OBJECTIVE: The purpose of this study was to expand our knowledge of familial IVF and to discuss its (extended) clinical characteristics. METHODS: We studied 601 family members and probands: 286 DPP6 risk-haplotype positive (haplotype-positive) and 315 DPP6 risk-haplotype negative (haplotype-negative) individuals. Clinical parameters, a combination of all-cause mortality and (aborted) cardiac arrest and differences between haplotype-positives and haplotype-negatives, were evaluated. RESULTS: There were no differences in electrocardiographic indices between haplotype-positives and haplotype-negatives, or between haplotype-positives with or without events. Cardiac magnetic resonance documented slightly larger ventricular volumes in haplotype-positives compared to controls (P <.05), but these were not clinically useful. Mortality and/or cardiac arrest occurred in 85 haplotype-positives (30%) and 18 haplotype-negatives (6%). Twenty-four haplotype-positives (8% male) were resuscitated from ventricular fibrillation (VF). Documented VF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall. Median survival in risk-haplotype haplotype-positives was 70 vs. 93 years for haplotype-negatives (P < .01), with a worse phenotype in males (median survival 63 vs. 83 years in females, P < .01). Implantable cardioverter-defibrillators were implanted in 99 patients (76 [77%] for primary prevention). Two arrhythmic events occurred in the primary prevention group during follow-up (5 ± 3 years). CONCLUSION: Despite our extensive analysis, the complexity in identifying asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.
BACKGROUND:Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and is notoriously difficult to manage because there are no clinical risk indicators for premature cardiac arrest. Previously, we identified a link between familial IVF and a risk haplotype on chromosome 7q36 (involving the arrhythmia gene DPP6). OBJECTIVE: The purpose of this study was to expand our knowledge of familial IVF and to discuss its (extended) clinical characteristics. METHODS: We studied 601 family members and probands: 286 DPP6 risk-haplotype positive (haplotype-positive) and 315 DPP6 risk-haplotype negative (haplotype-negative) individuals. Clinical parameters, a combination of all-cause mortality and (aborted) cardiac arrest and differences between haplotype-positives and haplotype-negatives, were evaluated. RESULTS: There were no differences in electrocardiographic indices between haplotype-positives and haplotype-negatives, or between haplotype-positives with or without events. Cardiac magnetic resonance documented slightly larger ventricular volumes in haplotype-positives compared to controls (P <.05), but these were not clinically useful. Mortality and/or cardiac arrest occurred in 85 haplotype-positives (30%) and 18 haplotype-negatives (6%). Twenty-four haplotype-positives (8% male) were resuscitated from ventricular fibrillation (VF). Documented VF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall. Median survival in risk-haplotype haplotype-positives was 70 vs. 93 years for haplotype-negatives (P < .01), with a worse phenotype in males (median survival 63 vs. 83 years in females, P < .01). Implantable cardioverter-defibrillators were implanted in 99 patients (76 [77%] for primary prevention). Two arrhythmic events occurred in the primary prevention group during follow-up (5 ± 3 years). CONCLUSION: Despite our extensive analysis, the complexity in identifying asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.
Authors: Christian Wolpert; Mara Vogel; Christian Nagel; Claudia Herrera-Siklody; Norman Rüb Journal: Herzschrittmacherther Elektrophysiol Date: 2017-05-22
Authors: Patrick N Cunningham; Zhiying Wang; Megan L Grove; Rhonda M Cooper-DeHoff; Amber L Beitelshees; Yan Gong; John G Gums; Julie A Johnson; Stephen T Turner; Eric Boerwinkle; Arlene B Chapman Journal: PLoS One Date: 2019-09-18 Impact factor: 3.240
Authors: Nicole D Dueker; Ashley Beecham; Liyong Wang; Chuanhui Dong; Ralph L Sacco; Susan H Blanton; Tatjana Rundek Journal: PLoS One Date: 2022-01-12 Impact factor: 3.240
Authors: Sanne A Groeneveld; Feddo P Kirkels; Maarten J Cramer; Reinder Evertz; Kristina H Haugaa; Pieter G Postema; Niek H J Prakken; Arco J Teske; Arthur A M Wilde; Birgitta K Velthuis; Robin Nijveldt; Rutger J Hassink Journal: J Am Heart Assoc Date: 2022-08-05 Impact factor: 6.106
Authors: Lisa M Verheul; Sanne A Groeneveld; Feddo P Kirkels; Paul G A Volders; Arco J Teske; Maarten J Cramer; Marco Guglielmo; Rutger J Hassink Journal: J Clin Med Date: 2022-08-10 Impact factor: 4.964