Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus

Judith N Ten Sande; Pieter G Postema; S Matthijs Boekholdt; Hanno L Tan; Jeroen F van der Heijden; Natasja M S de Groot; Paul G A Volders; Katja Zeppenfeld; Lucas V A Boersma; Eline A Nannenberg; Imke Christiaans; Arthur A M Wilde

doi:10.1016/j.hrthm.2015.12.006

Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus

Judith N Ten Sande, Pieter G Postema, S Matthijs Boekholdt, Hanno L Tan, Jeroen F van der Heijden, Natasja M S de Groot, Paul G A Volders, Katja Zeppenfeld, Lucas V A Boersma, Eline A Nannenberg, Imke Christiaans, Arthur A M Wilde

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and notoriously difficult to manage as 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: To expand our knowledge of familial-IVF and 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 MR documented slightly larger ventricular volumes in haplotype-positives compared to controls (p<0.05) 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 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<0.01), with a worse phenotype in males (median survival 63 vs. 83 years in females, p<0.01). ICDs were implanted in 99 patients (76 [77%] for primary prevention). Only one arrhythmic event occurred in the primary prevention group during follow-up (5±3years).

CONCLUSIONS: Indeed, despite our extensive analysis, the complexity to identify asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.

Original language	English
Pages (from-to)	905-912
Journal	Heart Rhythm
Volume	13
Issue number	4
DOIs	https://doi.org/10.1016/j.hrthm.2015.12.006
Publication status	Published - Apr 2016

Keywords

Sudden cardiac death
Idiopathic ventricular fibrillation
DPP6

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10.1016/j.hrthm.2015.12.006

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Ten Sande, J. N., Postema, P. G., Boekholdt, S. M., Tan, H. L., van der Heijden, J. F., de Groot, N. M. S., Volders, P. G. A., Zeppenfeld, K., Boersma, L. V. A., Nannenberg, E. A., Christiaans, I., & Wilde, A. A. M. (2016). Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus. Heart Rhythm, 13(4), 905-912. https://doi.org/10.1016/j.hrthm.2015.12.006

@article{75ab9e7fc515420eaf539a7449217688,

title = "Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus",

abstract = "BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and notoriously difficult to manage as 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: To expand our knowledge of familial-IVF and 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 MR documented slightly larger ventricular volumes in haplotype-positives compared to controls (p<0.05) 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 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<0.01), with a worse phenotype in males (median survival 63 vs. 83 years in females, p<0.01). ICDs were implanted in 99 patients (76 [77%] for primary prevention). Only one arrhythmic event occurred in the primary prevention group during follow-up (5±3years).CONCLUSIONS: Indeed, despite our extensive analysis, the complexity to identify asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.",

keywords = "Sudden cardiac death, Idiopathic ventricular fibrillation, DPP6",

author = "{Ten Sande}, {Judith N} and Postema, {Pieter G} and Boekholdt, {S Matthijs} and Tan, {Hanno L} and {van der Heijden}, {Jeroen F} and {de Groot}, {Natasja M S} and Volders, {Paul G A} and Katja Zeppenfeld and Boersma, {Lucas V A} and Nannenberg, {Eline A} and Imke Christiaans and Wilde, {Arthur A M}",

note = "Copyright {\textcopyright} 2015. Published by Elsevier Inc.",

year = "2016",

month = apr,

doi = "10.1016/j.hrthm.2015.12.006",

language = "English",

volume = "13",

pages = "905--912",

journal = "Heart Rhythm",

issn = "1547-5271",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus

AU - Ten Sande, Judith N

AU - Postema, Pieter G

AU - Boekholdt, S Matthijs

AU - Tan, Hanno L

AU - van der Heijden, Jeroen F

AU - de Groot, Natasja M S

AU - Volders, Paul G A

AU - Zeppenfeld, Katja

AU - Boersma, Lucas V A

AU - Nannenberg, Eline A

AU - Christiaans, Imke

AU - Wilde, Arthur A M

PY - 2016/4

Y1 - 2016/4

N2 - BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and notoriously difficult to manage as 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: To expand our knowledge of familial-IVF and 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 MR documented slightly larger ventricular volumes in haplotype-positives compared to controls (p<0.05) 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 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<0.01), with a worse phenotype in males (median survival 63 vs. 83 years in females, p<0.01). ICDs were implanted in 99 patients (76 [77%] for primary prevention). Only one arrhythmic event occurred in the primary prevention group during follow-up (5±3years).CONCLUSIONS: Indeed, despite our extensive analysis, the complexity to identify asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.

AB - BACKGROUND: Familial idiopathic ventricular fibrillation (IVF) is a severe disease entity and notoriously difficult to manage as 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: To expand our knowledge of familial-IVF and 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 MR documented slightly larger ventricular volumes in haplotype-positives compared to controls (p<0.05) 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 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<0.01), with a worse phenotype in males (median survival 63 vs. 83 years in females, p<0.01). ICDs were implanted in 99 patients (76 [77%] for primary prevention). Only one arrhythmic event occurred in the primary prevention group during follow-up (5±3years).CONCLUSIONS: Indeed, despite our extensive analysis, the complexity to identify asymptomatic IVF family members at risk for future arrhythmias based on clinical parameters is once more demonstrated.

KW - Sudden cardiac death

KW - Idiopathic ventricular fibrillation

KW - DPP6

U2 - 10.1016/j.hrthm.2015.12.006

DO - 10.1016/j.hrthm.2015.12.006

M3 - Article

C2 - 26681609

SN - 1547-5271

VL - 13

SP - 905

EP - 912

JO - Heart Rhythm

JF - Heart Rhythm

IS - 4

ER -

Detailed Characterization of Familial Idiopathic Ventricular Fibrillation Linked to The DPP6 Locus

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Keywords

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