Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation.
Journal article

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation.

  • Shoemaker MB 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.).
  • Husser D Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Roselli C 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.).
  • Al Jazairi M 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.).
  • Chrispin J Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.C., H.C.).
  • Kühne M University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Neumann B Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Knight S Intermountain Heart Institute, Intermountain Medical Center, Murray (S. Knight, V.J.).
  • Sun H Department of Quantitative Health Sciences (H.S., J.B.), Lerner Research Institute, Cleveland Clinic, OH.
  • Mohanty S Texas Cardiac Arrhythmia Institute, Austin, TX (S.M., A.N.).
  • Shaffer C 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.).
  • Thériault S Population Health Research Institute, McMaster University, Hamilton, ON, Canada (S.T., D.C.).
  • Rinke LL 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.).
  • Siland JE 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.).
  • Crawford DM 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.).
  • Ueberham L Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Zardkoohi O Departments of Cardiovascular Medicine and Molecular Cardiology, Heart and Vascular Institute (O.Z., M.C.), Lerner Research Institute, Cleveland Clinic, OH.
  • Büttner P Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Geelhoed B 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.).
  • Blum S University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Aeschbacher S University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Smith JD Department of Cellular and Molecular Medicine (J.D.S.), Lerner Research Institute, Cleveland Clinic, OH.
  • Van Wagoner DR Department of Molecular Cardiology (D.R.V.W.), Lerner Research Institute, Cleveland Clinic, OH.
  • Freudling R Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Müller-Nurasyid M Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg (R.F., M.M.-N.).
  • Montgomery J 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.).
  • Yoneda Z 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.).
  • Wells Q 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.).
  • Issa T 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.).
  • Weeke P 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.).
  • Jacobs V Intermountain Heart Institute, Intermountain Medical Center, Murray (S. Knight, V.J.).
  • Van Gelder IC 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.).
  • Hindricks G Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Barnard J Department of Quantitative Health Sciences (H.S., J.B.), Lerner Research Institute, Cleveland Clinic, OH.
  • Calkins H Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.C., H.C.).
  • Darbar D Division of Cardiology, Department of Medicine, University of Illinois Health, Chicago (D.D.).
  • Michaud G 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.).
  • Kääb S Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Ellinor P 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.).
  • Natale A Texas Cardiac Arrhythmia Institute, Austin, TX (S.M., A.N.).
  • Chung M Departments of Cardiovascular Medicine and Molecular Cardiology, Heart and Vascular Institute (O.Z., M.C.), Lerner Research Institute, Cleveland Clinic, OH.
  • Nazarian S Division of Cardiology, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.N.).
  • Cutler MJ Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (M.J.C.).
  • Sinner MF Department of Medicine, University Hospital Munich, Ludwig Maximilians University of Munich, Germany (B.N., R.F., S. Kääb, M.F.S.).
  • Conen D University Hospital Basel, Switzerland (M.K., S.B., S.A., D.C.).
  • Rienstra M 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.).
  • Bollmann A Heart Center Leipzig, Department of Electrophysiology, Leipzig Heart Institute, University of Leipzig, Germany (D.H., L.U., P.B., G.H., A.B.).
  • Roden DM Animal, Dairy, and Veterinary Sciences, Utah State University, Logan (D.M.R.).
  • Lubitz S 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.).
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  • 2020-02-21
Published in:
  • Circulation. Arrhythmia and electrophysiology. - 2020
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/90945
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