Common Genetic Variants and Response to Atrial Fibrillation Ablation

DOI Web Site 4 Citations
  • M. Benjamin Shoemaker
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Andreas Bollmann
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Steven A. Lubitz
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Laura Ueberham
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Harsimran Saini
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Jay Montgomery
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Todd Edwards
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Zachary Yoneda
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Moritz F. Sinner
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Arash Arya
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Philipp Sommer
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Jessica Delaney
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Sandeep K. Goyal
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Pablo Saavedra
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Arvindh Kanagasundram
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • S. Patrick Whalen
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Dan M. Roden
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Gerhard Hindricks
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Christopher R. Ellis
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Patrick T. Ellinor
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Dawood Darbar
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
  • Daniela Husser
    From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).

Description

<jats:sec> <jats:title>Background—</jats:title> <jats:p> Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near <jats:italic>PITX2</jats:italic> ), 1q21 (rs13376333 in <jats:italic>KCNN3</jats:italic> ), and 16q22 (rs7193343 in <jats:italic>ZFHX3</jats:italic> ) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6]; <jats:italic>P</jats:italic> =0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.</jats:p> </jats:sec>

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