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5. The Dutch Idiopathic Ventricular Fibrillation Registry: progress report on the quest to identify the unidentifiable

Author

Team Onderzoek, Arts Assistenten Cardiologie, Cardiologie, Team Medisch, Circulatory Health, Verheul, Lisa M., Groeneveld, Sanne A., Stoks, Job, Hoeksema, Wiert F., Cluitmans, Matthijs J.M., Postema, Pieter G., Wilde, Arthur A.M., Volders, Paul G.A., Hassink, Rutger J., Team Onderzoek, Arts Assistenten Cardiologie, Cardiologie, Team Medisch, Circulatory Health, Verheul, Lisa M., Groeneveld, Sanne A., Stoks, Job, Hoeksema, Wiert F., Cluitmans, Matthijs J.M., Postema, Pieter G., Wilde, Arthur A.M., Volders, Paul G.A., and Hassink, Rutger J.

Published
2024

6. The Genetic Basis of Apparently Idiopathic Ventricular Fibrillation – a Retrospective Overview

Author

Verheul, Lisa M, primary, van der Ree, Martijn H, additional, Groeneveld, Sanne A, additional, Mulder, Bart A, additional, Christiaans, Imke, additional, Kapel, Gijs F L, additional, Alings, Marco, additional, Bootsma, Marianne, additional, Barge-Schaapveld, Daniela Q C M, additional, Balt, Jippe C, additional, Yap, Sing-Chien, additional, Krapels, Ingrid P C, additional, Ter Bekke, Rachel M A, additional, Volders, Paul G A, additional, van der Crabben, Saskia N, additional, Postema, Pieter G, additional, Wilde, Arthur A M, additional, Dooijes, Dennis, additional, Baas, Annette F, additional, and Hassink, Rutger J, additional

Published
2023
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8. Atrial fibrillation begets ventricular fibrillation when the AV node fails

Author

Team Onderzoek, Cardiologie, Team Medisch, Circulatory Health, Verheul, Lisa M., Groeneveld, Sanne A., Tuinenburg, Anton E., Hassink, Rutger J., Team Onderzoek, Cardiologie, Team Medisch, Circulatory Health, Verheul, Lisa M., Groeneveld, Sanne A., Tuinenburg, Anton E., and Hassink, Rutger J.

Published
2023

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

Author

Verheul, Lisa M., Van Der Ree, Martijn H., Groeneveld, Sanne A., Mulder, Bart A., Christiaans, Imke, Kapel, Gijs F.L., Alings, Marco, Bootsma, Marianne, Barge-Schaapveld, Daniela Q.C.M., Balt, Jippe C., Yap, Sing Chien, Krapels, Ingrid P.C., Ter Bekke, Rachel M.A., Volders, Paul G.A., Van Der Crabben, Saskia N., Postema, Pieter G., Wilde, Arthur A.M., Dooijes, Dennis, Baas, Annette F., Hassink, Rutger J., Verheul, Lisa M., Van Der Ree, Martijn H., Groeneveld, Sanne A., Mulder, Bart A., Christiaans, Imke, Kapel, Gijs F.L., Alings, Marco, Bootsma, Marianne, Barge-Schaapveld, Daniela Q.C.M., Balt, Jippe C., Yap, Sing Chien, Krapels, Ingrid P.C., Ter Bekke, Rachel M.A., Volders, Paul G.A., Van Der Crabben, Saskia N., Postema, Pieter G., Wilde, Arthur A.M., Dooijes, Dennis, Baas, Annette F., and Hassink, Rutger J.

Abstract

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.

Published
2023

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

Author

Bergeman, Auke T., Hoeksema, Wiert F., van der Ree, Martijn H., Boersma, Lucas V.A., Yap, Sing Chien, Verheul, Lisa M., Hassink, Rutger J., van der Crabben, Saskia N., Volders, Paul G.A., van der Werf, Christian, Wilde, Arthur A.M., Postema, Pieter G., Bergeman, Auke T., Hoeksema, Wiert F., van der Ree, Martijn H., Boersma, Lucas V.A., Yap, Sing Chien, Verheul, Lisa M., Hassink, Rutger J., van der Crabben, Saskia N., Volders, Paul G.A., van der Werf, Christian, Wilde, Arthur A.M., and Postema, Pieter G.

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.

Published
2023

11. The Genetic Basis of Apparently Idiopathic Ventricular Fibrillation - a Retrospective Overview

Author

Team Onderzoek, Cardiovasculaire Epi Team 10, Genetica, Genetica Sectie Genoomdiagnostiek, Circulatory Health, Genetica Klinische Genetica, Team Medisch, Verheul, Lisa M, van der Ree, Martijn H, Groeneveld, Sanne A, Mulder, Bart A, Christiaans, Imke, Kapel, Gijs F L, Alings, Marco, Bootsma, Marianne, Barge-Schaapveld, Daniela Q C M, Balt, Jippe C, Yap, Sing-Chien, Krapels, Ingrid P C, Ter Bekke, Rachel M A, Volders, Paul G A, van der Crabben, Saskia N, Postema, Pieter G, Wilde, Arthur A M, Dooijes, Dennis, Baas, Annette F, Hassink, Rutger J, Team Onderzoek, Cardiovasculaire Epi Team 10, Genetica, Genetica Sectie Genoomdiagnostiek, Circulatory Health, Genetica Klinische Genetica, Team Medisch, Verheul, Lisa M, van der Ree, Martijn H, Groeneveld, Sanne A, Mulder, Bart A, Christiaans, Imke, Kapel, Gijs F L, Alings, Marco, Bootsma, Marianne, Barge-Schaapveld, Daniela Q C M, Balt, Jippe C, Yap, Sing-Chien, Krapels, Ingrid P C, Ter Bekke, Rachel M A, Volders, Paul G A, van der Crabben, Saskia N, Postema, Pieter G, Wilde, Arthur A M, Dooijes, Dennis, Baas, Annette F, and Hassink, Rutger J

Published
2023

12. Importance of Systematic Diagnostic Testing in Idiopathic Ventricular Fibrillation

Author

Groeneveld, Sanne A., primary, Verheul, Lisa M., additional, van der Ree, Martijn H., additional, Mulder, Bart A., additional, Scholten, Marcoen F., additional, Alings, Marco, additional, van der Voort, Pepijn, additional, Bootsma, Marianne, additional, Evertz, Reinder, additional, Balt, Jippe C., additional, Yap, Sing-Chien, additional, Doevendans, Pieter.A.F.M., additional, Postema, Pieter G., additional, Wilde, Arthur A.M., additional, Volders, Paul G.A., additional, and Hassink, Rutger J., additional

Published
2023
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13. The Importance of Systematic Diagnostic Testing in Idiopathic Ventricular Fibrillation: Results From the Dutch iVF-Registry

Author

Groeneveld, Sanne A, Verheul, Lisa M, van der Ree, Martijn H, Mulder, Bart A, Scholten, Marcoen F, Alings, Marco, van der Voort, Pepijn, Bootsma, Marianne, Evertz, Reinder, Balt, Jippe C, Yap, Sing-Chien, Doevendans, Pieter A F M, Postema, Pieter G, Wilde, Arthur A M, Volders, Paul G A, Hassink, Rutger J, Cardiology, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H04 Arrhythmogenesis and cardiogenetics

Abstract

BACKGROUND: Idiopathic ventricular fibrillation (iVF) is a diagnosis of exclusion. Systematic diagnostic testing is important to exclude alternative causes for VF. The early use of "high yield" testing, including cardiac magnetic resonance (CMR), exercise testing, and sodium channel blocker provocation, has been increasingly recognized. OBJECTIVES: The purpose of this study was to investigate the importance and consistency of systematic diagnostic testing in iVF. METHODS: This study included 423 iVF patients from 11 large secondary and tertiary hospitals in the Netherlands. Clinical characteristics and diagnostic testing data were ascertained. RESULTS: IVF patients experienced the index event at a median age of 40 years (IQR: 28-52 years), and 61% were men. The median follow-up time was 6 years (IQR: 2-12 years). Over the years, "high yield" diagnostic tests were increasingly performed (mean 68% in 2000-2010 vs 75% in 2011-2021; P < 0.001). During follow-up, 38 patients (9%) originally labeled as iVF received an alternative diagnosis. Patients in whom "high-yield" diagnostic tests were consistently performed during the initial work-up received an alternative diagnosis less frequently during follow-up (HR: 0.439; 95% CI: 0.219-0.878; P = 0.020). Patients who received an alternative diagnosis during follow-up had a worse prognosis in terms of cardiac death (P = 0.012) with a trend toward more implantable cardioverter-defibrillator therapy (P = 0.055). CONCLUSIONS: Although adherence to (near) complete diagnostic testing in this population of iVF patients increased over the years, patients with iVF still undergo varying levels of diagnostic evaluation. The latter leads to initial underdiagnosis of alternative conditions and is associated with a worse prognosis. Our results underscore the importance of early systematic diagnostic assessment in patients with apparent iVF.

Published
2023

16. State-of-the-Art Multimodality Imaging in Sudden Cardiac Arrest with Focus on Idiopathic Ventricular Fibrillation: A Review

Author

Cardiologie, Team Onderzoek, Team Medisch, Circulatory Health, Verheul, Lisa M., Groeneveld, Sanne A., Kirkels, Feddo P., Volders, Paul G.A., Teske, Arco J., Cramer, Maarten J., Guglielmo, Marco, Hassink, Rutger J., Cardiologie, Team Onderzoek, Team Medisch, Circulatory Health, Verheul, Lisa M., Groeneveld, Sanne A., Kirkels, Feddo P., Volders, Paul G.A., Teske, Arco J., Cramer, Maarten J., Guglielmo, Marco, and Hassink, Rutger J.

Published
2022

17. [A woman with shortness of breath and a rash].

Author

Verheul LM and Hardeman HA

Subjects
Aged, Dyspnea etiology, Female, Herpesvirus 3, Human, Humans, Exanthema etiology, Herpes Zoster
Abstract

A 74-year-old woman presented with progressive dyspnoea which started a few days after developing a unilateral dermatomal rash characteristic for herpes zoster at dermatome C4-C5. X-ray of the thorax showed an elevated hemidiaphragm ipsilateral of the skin abnormalities. Cervical herpes zoster is a rare cause of a unilateral elevated hemidiaphragm.

Published
2021

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