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 - Kaä¨b, 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
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020
Y1 - 2020
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 - atrial fibrillation
KW - genetic variation
KW - genetics
KW - phenotype
KW - pulmonary veins
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U2 - 10.1161/CIRCEP.119.007676
DO - 10.1161/CIRCEP.119.007676
M3 - Article
C2 - 32078373
AN - SCOPUS:85082093298
SN - 1941-3149
JO - Circulation: Arrhythmia and Electrophysiology
JF - Circulation: Arrhythmia and Electrophysiology
M1 - e007676
ER -