Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

M Benjamin Shoemaker; Daniela Husser; Carolina Roselli; Meelad Al Jazairi; Jonathan Chrispin; Michael Kühne; Benjamin Neumann; Stacey Knight; Han Sun; Sanghamitra Mohanty; Christian Shaffer; Sébastien Thériault; Lauren Lee Rinke; Joylene E Siland; Diane M Crawford; Laura Ueberham; Omeed Zardkoohi; Petra Büttner; Bastiaan Geelhoed; Steffen Blum; Stefanie Aeschbacher; Jonathan D Smith; David R Van Wagoner; Rebecca Freudling; Martina Müller-Nurasyid; Jay Montgomery; Zachary Yoneda; Quinn Wells; Tariq Issa; Peter Weeke; Victoria Jacobs; Isabelle C Van Gelder; Gerhard Hindricks; John Barnard; Hugh Calkins; Dawood Darbar; Greg Michaud; Stefan Kääb; Patrick Ellinor; Andrea Natale; Mina Chung; Saman Nazarian; Michael J Cutler; Moritz F Sinner; David Conen; Michiel Rienstra; Andreas Bollmann; Dan M Roden; Steven Lubitz

doi:10.1161/CIRCEP.119.007676

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

M Benjamin Shoemaker, Daniela Husser, Carolina Roselli, Meelad Al Jazairi, Jonathan Chrispin, Michael Kühne, Benjamin Neumann, Stacey Knight, Han Sun, Sanghamitra Mohanty, Christian Shaffer, Sébastien Thériault, Lauren Lee Rinke, Joylene E Siland, Diane M Crawford, Laura Ueberham, Omeed Zardkoohi, Petra Büttner, Bastiaan Geelhoed, Steffen BlumStefanie Aeschbacher, Jonathan D Smith, David R Van Wagoner, Rebecca Freudling, Martina Müller-Nurasyid, Jay Montgomery, Zachary Yoneda, Quinn Wells, Tariq Issa, Peter Weeke, Victoria Jacobs, Isabelle C Van Gelder, Gerhard Hindricks, John Barnard, Hugh Calkins, Dawood Darbar, Greg Michaud, Stefan Kääb, Patrick Ellinor, Andrea Natale, Mina Chung, Saman Nazarian, Michael J Cutler, Moritz F Sinner, David Conen, Michiel Rienstra, Andreas Bollmann, Dan M Roden, Steven Lubitz

Afdeling for Hjertesygdomme

43 Citationer (Scopus)

Abstract

BACKGROUND: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.

METHODS: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.

RESULTS: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).

CONCLUSIONS: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Originalsprog	Engelsk
Tidsskrift	Circulation. Arrhythmia and Electrophysiology
Vol/bind	13
Udgave nummer	3
Sider (fra-til)	e007676
ISSN	1941-3149
DOI	https://doi.org/10.1161/CIRCEP.119.007676
Status	Udgivet - mar. 2020

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10.1161/CIRCEP.119.007676

Citationsformater

Shoemaker, M. B., Husser, D., Roselli, C., Al Jazairi, M., Chrispin, J., Kühne, M., Neumann, B., Knight, S., Sun, H., Mohanty, S., Shaffer, C., Thériault, S., Rinke, L. L., Siland, J. E., Crawford, D. M., Ueberham, L., Zardkoohi, O., Büttner, P., Geelhoed, B., ... Lubitz, S. (2020). Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation. Circulation. Arrhythmia and Electrophysiology, 13(3), e007676. https://doi.org/10.1161/CIRCEP.119.007676

Shoemaker, MB, Husser, D, Roselli, C, Al Jazairi, M, Chrispin, J, Kühne, M, Neumann, B, Knight, S, Sun, H, Mohanty, S, Shaffer, C, Thériault, S, Rinke, LL, Siland, JE, Crawford, DM, Ueberham, L, Zardkoohi, O, Büttner, P, Geelhoed, B, Blum, S, Aeschbacher, S, Smith, JD, Van Wagoner, DR, Freudling, R, Müller-Nurasyid, M, Montgomery, J, Yoneda, Z, Wells, Q, Issa, T, Weeke, P, Jacobs, V, Van Gelder, IC, Hindricks, G, Barnard, J, Calkins, H, Darbar, D, Michaud, G, Kääb, S, Ellinor, P, Natale, A, Chung, M, Nazarian, S, Cutler, MJ, Sinner, MF, Conen, D, Rienstra, M, Bollmann, A, Roden, DM & Lubitz, S 2020, 'Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation', Circulation. Arrhythmia and Electrophysiology, bind 13, nr. 3, s. e007676. https://doi.org/10.1161/CIRCEP.119.007676

@article{13d0f84e29d941b18454f44434eddd3c,

title = "Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation",

abstract = "BACKGROUND: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.METHODS: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.RESULTS: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).CONCLUSIONS: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.",

keywords = "Aged, Atrial Fibrillation/genetics, Body Surface Potential Mapping/methods, Catheter Ablation, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Multifactorial Inheritance/genetics, Polymorphism, Single Nucleotide, Preoperative Period, Prognosis, Prospective Studies, Recurrence",

author = "Shoemaker, {M Benjamin} and Daniela Husser and Carolina Roselli and {Al Jazairi}, Meelad and Jonathan Chrispin and Michael K{\"u}hne and Benjamin Neumann and Stacey Knight and Han Sun and Sanghamitra Mohanty and Christian Shaffer and S{\'e}bastien Th{\'e}riault and Rinke, {Lauren Lee} and Siland, {Joylene E} and Crawford, {Diane M} and Laura Ueberham and Omeed Zardkoohi and Petra B{\"u}ttner and Bastiaan Geelhoed and Steffen Blum and Stefanie Aeschbacher and Smith, {Jonathan D} and {Van Wagoner}, {David R} and Rebecca Freudling and Martina M{\"u}ller-Nurasyid and Jay Montgomery and Zachary Yoneda and Quinn Wells and Tariq Issa and Peter Weeke and Victoria Jacobs and {Van Gelder}, {Isabelle C} and Gerhard Hindricks and John Barnard and Hugh Calkins and Dawood Darbar and Greg Michaud and Stefan K{\"a}{\"a}b and Patrick Ellinor and Andrea Natale and Mina Chung and Saman Nazarian and Cutler, {Michael J} and Sinner, {Moritz F} and David Conen and Michiel Rienstra and Andreas Bollmann and Roden, {Dan M} and Steven Lubitz",

year = "2020",

month = mar,

doi = "10.1161/CIRCEP.119.007676",

language = "English",

volume = "13",

pages = "e007676",

journal = "Circulation. Arrhythmia and Electrophysiology",

issn = "1941-3149",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

TY - JOUR

T1 - Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

AU - Shoemaker, M Benjamin

AU - Husser, Daniela

AU - Roselli, Carolina

AU - Al Jazairi, Meelad

AU - Chrispin, Jonathan

AU - Kühne, Michael

AU - Neumann, Benjamin

AU - Knight, Stacey

AU - Sun, Han

AU - Mohanty, Sanghamitra

AU - Shaffer, Christian

AU - Thériault, Sébastien

AU - Rinke, Lauren Lee

AU - Siland, Joylene E

AU - Crawford, Diane M

AU - Ueberham, Laura

AU - Zardkoohi, Omeed

AU - Büttner, Petra

AU - Geelhoed, Bastiaan

AU - Blum, Steffen

AU - Aeschbacher, Stefanie

AU - Smith, Jonathan D

AU - Van Wagoner, David R

AU - Freudling, Rebecca

AU - Müller-Nurasyid, Martina

AU - Montgomery, Jay

AU - Yoneda, Zachary

AU - Wells, Quinn

AU - Issa, Tariq

AU - Weeke, Peter

AU - Jacobs, Victoria

AU - Van Gelder, Isabelle C

AU - Hindricks, Gerhard

AU - Barnard, John

AU - Calkins, Hugh

AU - Darbar, Dawood

AU - Michaud, Greg

AU - Kääb, Stefan

AU - Ellinor, Patrick

AU - Natale, Andrea

AU - Chung, Mina

AU - Nazarian, Saman

AU - Cutler, Michael J

AU - Sinner, Moritz F

AU - Conen, David

AU - Rienstra, Michiel

AU - Bollmann, Andreas

AU - Roden, Dan M

AU - Lubitz, Steven

PY - 2020/3

Y1 - 2020/3

N2 - BACKGROUND: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.METHODS: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.RESULTS: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).CONCLUSIONS: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

AB - BACKGROUND: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.METHODS: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.RESULTS: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).CONCLUSIONS: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

KW - Aged

KW - Atrial Fibrillation/genetics

KW - Body Surface Potential Mapping/methods

KW - Catheter Ablation

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Middle Aged

KW - Multifactorial Inheritance/genetics

KW - Polymorphism, Single Nucleotide

KW - Preoperative Period

KW - Prognosis

KW - Prospective Studies

KW - Recurrence

U2 - 10.1161/CIRCEP.119.007676

DO - 10.1161/CIRCEP.119.007676

M3 - Journal article

C2 - 32078373

SN - 1941-3149

VL - 13

SP - e007676

JO - Circulation. Arrhythmia and Electrophysiology

JF - Circulation. Arrhythmia and Electrophysiology

IS - 3

ER -

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

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