Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

DOI Web Site 被引用文献2件
  • M. Benjamin Shoemaker
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Daniela Husser
    Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Carolina Roselli
    Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, MA (C.R., P.E., S.L.).
  • Meelad Al Jazairi
    Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (M.A.J., J.E.S., B.G., I.C.V.G., M.R.).
  • Jonathan Chrispin
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.C., H.C.).
  • Michael Kühne
    University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Benjamin Neumann
    Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Stacey Knight
    Intermountain Heart Institute, Intermountain Medical Center, Murray (S. Knight, V.J.).
  • Han Sun
    Department of Quantitative Health Sciences (H.S., J.B.), Lerner Research Institute, Cleveland Clinic, OH.
  • Sanghamitra Mohanty
    Texas Cardiac Arrhythmia Institute, Austin, TX (S.M., A.N.).
  • Christian Shaffer
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Sébastien Thériault
    Population Health Research Institute, McMaster University, Hamilton, ON, Canada (S.T., D.C.).
  • Lauren Lee Rinke
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Joylene E. Siland
    Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (M.A.J., J.E.S., B.G., I.C.V.G., M.R.).
  • Diane M. Crawford
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Laura Ueberham
    Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Omeed Zardkoohi
    Departments of Cardiovascular Medicine and Molecular Cardiology, Heart and Vascular Institute (O.Z., M.C.), Lerner Research Institute, Cleveland Clinic, OH.
  • Petra Büttner
    Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Bastiaan Geelhoed
    Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (M.A.J., J.E.S., B.G., I.C.V.G., M.R.).
  • Steffen Blum
    University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Stefanie Aeschbacher
    University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Jonathan D. Smith
    Department of Cellular and Molecular Medicine (J.D.S.), Lerner Research Institute, Cleveland Clinic, OH.
  • David R. Van Wagoner
    Department of Molecular Cardiology (D.R.V.W.), Lerner Research Institute, Cleveland Clinic, OH.
  • Rebecca Freudling
    Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Martina Müller-Nurasyid
    Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg (R.F., M.M.-N.).
  • Jay Montgomery
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Zachary Yoneda
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Quinn Wells
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Tariq Issa
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Peter Weeke
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Victoria Jacobs
    Intermountain Heart Institute, Intermountain Medical Center, Murray (S. Knight, V.J.).
  • Isabelle C. Van Gelder
    Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (M.A.J., J.E.S., B.G., I.C.V.G., M.R.).
  • Gerhard Hindricks
    Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • John Barnard
    Department of Quantitative Health Sciences (H.S., J.B.), Lerner Research Institute, Cleveland Clinic, OH.
  • Hugh Calkins
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.C., H.C.).
  • Dawood Darbar
    Division of Cardiology, Department of Medicine, University of Illinois Health, Chicago (D.D.).
  • Greg Michaud
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (M.B.S., C.S., L.L.R., D.M.C., J.M., Z.Y., Q.W., T.I., P.W., G.M.).
  • Stefan Kääb
    Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Patrick Ellinor
    Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, MA (C.R., P.E., S.L.).
  • Andrea Natale
    Texas Cardiac Arrhythmia Institute, Austin, TX (S.M., A.N.).
  • Mina Chung
    Departments of Cardiovascular Medicine and Molecular Cardiology, Heart and Vascular Institute (O.Z., M.C.), Lerner Research Institute, Cleveland Clinic, OH.
  • Saman Nazarian
    Division of Cardiology, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.N.).
  • Michael J. Cutler
    Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (M.J.C.).
  • Moritz F. Sinner
    Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • David Conen
    University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Michiel Rienstra
    Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (M.A.J., J.E.S., B.G., I.C.V.G., M.R.).
  • Andreas Bollmann
    Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Dan M. Roden
    Animal, Dairy, and Veterinary Sciences, Utah State University, Logan (D.M.R.).
  • Steven Lubitz
    Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Program in Medical and Population Genetics, Cambridge, MA (C.R., P.E., S.L.).

説明

<jats:sec> <jats:title>Background:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> 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 ( <jats:italic>P</jats:italic> <0.001) and had fewer clinical risk factors for AF ( <jats:italic>P</jats:italic> =0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22–1.58]; <jats:italic>P</jats:italic> <0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19–1.46]; <jats:italic>P</jats:italic> <0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80–0.97]; <jats:italic>P</jats:italic> =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]; <jats:italic>P</jats:italic> =0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98–1.15]; <jats:italic>P</jats:italic> =0.13). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>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.</jats:p> </jats:sec>

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