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Plasma Profiles of Matrix Metalloproteinases and Tissue Inhibitors of the Metalloproteinases Predict Recurrence of Atrial Fibrillation Following Cardioversion

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Abstract

Atrial fibrosis is considered to contribute to atrial fibrillation (AF) recurrence following cardioversion. This study tested the hypothesis that circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can predict AF recurrence postcardioversion. Precardioversion plasma samples (n = 82) were assayed for MMPs (eight types), TIMPs (all four types), N-terminus pro B-type natriuretic peptide, and high-sensitivity C-reactive protein levels. Patients were followed for AF recurrence postcardioversion. Despite 100 % restoration of sinus rhythm, 36 (44 %) reverted to AF within 3 months. Left atrial volume was increased in patients in whom AF recurred. Precardioversion MMP-9 was higher and TIMP-4 lower with AF recurrence. MMP-9, MMP-3, and TIMP-4 independently predicted AF recurrence. In multivariate analysis, combination of MMP-9, MMP-3, and TIMP-4 increased prediction of AF recurrence. Circulating levels of MMPs and TIMPs predict AF recurrence postcardioversion and may be used in a novel biomarker panel to guide AF stratification and therapy.

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Funding Source(s)

This work was performed as part of the Tourville Arrhythmia Center and was supported by the National Institute of Health grants HL057952, HL059165, HL095608, a Merit Award from the Veterans’ Affairs Health Administration, and a philanthropic contribution from Robert and Molly Tarr Foundation to the Division of Cardiology, Medical University of South Carolina.

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Authors and Affiliations

  1. Division of Cardiothoracic Surgery, Medical University of South Carolina, 770 MUSC Complex, Suite 326, Charleston, SC, 29425, USA

    Rupak Mukherjee, Robert E. Stroud & Allison D. Rice

  2. Department of Cardiology, Yale University, New Haven, CT, USA

    Joseph G. Akar

  3. Division of Cardiology, Medical University of South Carolina, Charleston, SC, USA

    J. Marcus Wharton, Deborah K. Adams, Catherine D. McClure & Michael R. Gold

  4. University of Texas Health Sciences Center, San Antonio, TX, 78229, USA

    Stacia M. DeSantis

  5. Department of Medicine, School of Medicine, University of South Carolina, Columbia, SC, USA

    Francis G. Spinale

Authors
  1. Rupak Mukherjee
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  2. Joseph G. Akar
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  3. J. Marcus Wharton
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  4. Deborah K. Adams
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  5. Catherine D. McClure
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  6. Robert E. Stroud
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  7. Allison D. Rice
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  8. Stacia M. DeSantis
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  9. Francis G. Spinale
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  10. Michael R. Gold
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Corresponding author

Correspondence to Rupak Mukherjee.

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Clinical Significance

Atrial fibrillation (AF), which is associated with enlargement of the left atrium and remodeling of the extracellular matrix within the atrial myocardium, can recur in almost 50 % of patients within 3–6 months following electrical cardioversion. This study provides proof of concept that a panel of biomarkers comprising of proteins key to extracellular matrix remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases) may be used to prognosticate postcardioversion AF recurrence independent of changes in the left atrial volume.

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Mukherjee, R., Akar, J.G., Wharton, J.M. et al. Plasma Profiles of Matrix Metalloproteinases and Tissue Inhibitors of the Metalloproteinases Predict Recurrence of Atrial Fibrillation Following Cardioversion. J. of Cardiovasc. Trans. Res. 6, 528–535 (2013). https://doi.org/10.1007/s12265-013-9471-2

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  • DOI: https://doi.org/10.1007/s12265-013-9471-2

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