Skip to main content

Advertisement

SpringerLink
Log in

Increased levels of inflammatory and extracellular matrix turnover biomarkers persist despite reverse atrial structural remodeling during the first year after atrial fibrillation ablation

  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Purpose

Left atrial (LA) remodeling associated with atrial fibrillation (AF) is known to be related to inflammation and collagen turnover. We investigated the changes in the biomarkers of inflammation and collagen turnover in relation to LA reverse remodeling during the 1st year after AF ablation.

Methods

Biomarkers of inflammation [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)] and collagen turnover [matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), transforming growth factor beta 1 (TGF-β1)], as well as asymmetric dimethylarginine (ADMA) and adiponectin levels were measured, and echocardiographic measurements were obtained before and 3, 6, and 12 months after ablation in 60 AF patients (49 males; age, 57.6 ± 10.9 years).

Results

During a 12.1 (11.5–12.9)-month follow-up period, AF recurred in 29 patients (48 %). Neither the LA volume (LAV) nor the left ventricular ejection fraction (LVEF) changed significantly during the 1st year in this group, but the LAV decreased significantly, and the LVEF increased significantly in the nonrecurrence group. The hs-CRP and IL-6 decreased after ablation but returned near to baseline levels in both groups by 12 months. The MMP-2 remained increased during the 1st year in both groups, whereas the TIMP-2 increased markedly in the nonrecurrence group but did not change substantially in the recurrence group. The TGF-β1 increased in both groups, but the change was less pronounced in the recurrence group. The ADMA and adiponectin levels did not change substantially in either group.

Conclusions

Despite reverse remodeling, the inflammation and collagen turnover biomarker levels are quite progressive during the 1st year after ablation and may explain the late AF recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Cappato, R., Calkins, H., Chen, S. A., Davies, W., Iesaka, Y., Kalman, J., et al. (2010). Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation Arrhythmia and Electrophysiology, 3(1), 32–38.

    Article  PubMed  Google Scholar 

  2. Nguyen, B. L., Fishbein, M. C., Chen, L. S., Chen, P. S., & Masroor, S. (2009). Histopathological substrate for chronic atrial fibrillation in humans. Heart Rhythm, 6(4), 454–460.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Engelmann, M. D., & Svendsen, J. H. (2005). Inflammation in the genesis and perpetuation of atrial fibrillation. European Heart Journal, 26(20), 2083–2092.

    Article  CAS  PubMed  Google Scholar 

  4. Casaclang-Verzosa, G., Gersh, B. J., & Tsang, T. S. (2008). Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation. Journal of the American College of Cardiology, 51(1), 1–11.

    Article  PubMed  Google Scholar 

  5. Xu, J., Cui, G., Esmalian, F., Plunkett, M., Marelli, D., Ardehali, A., et al. (2004). Atrial extracellular matrix remodeling and the maintenance of atrial fibrillation. Circulation, 109(3), 363–368.

    Article  CAS  PubMed  Google Scholar 

  6. Nakano, Y., Niida, S., Dote, K., Takenaka, S., Hirao, H., Miura, F., et al. (2004). Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation. Journal of the American College of Cardiology, 43(5), 818–825.

    Article  CAS  PubMed  Google Scholar 

  7. Conway, D. S., Buggins, P., Hughes, E., & Lip, G. Y. (2004). Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. Journal of the American College of Cardiology, 43(11), 2075–2082.

    Article  CAS  PubMed  Google Scholar 

  8. Richter, B., Gwechenberger, M., Socas, A., Zorn, G., Albinni, S., Marx, M., et al. (2011). Time course of markers of tissue repair after ablation of atrial fibrillation and their relation to left atrial structural changes and clinical ablation outcome. International Journal of Cardiology, 152(2), 231–236.

    Article  PubMed  Google Scholar 

  9. Okumura, Y., Watanabe, I., Nakai, T., Ohkubo, K., Kofune, T., Kofune, M., et al. (2011). Impact of biomarkers of inflammation and extracellular matrix turnover on the outcome of atrial fibrillation. Journal of Cardiovascular Electrophysiology, 22(9), 987–993.

    Article  PubMed  Google Scholar 

  10. Kim, S. K., Park, J. H., Kim, J. Y., Choi, J. I., Joung, B., Lee, M. H., et al. (2011). High plasma concentrations of transforming growth factor-β and tissue inhibitor of metalloproteinase-1: potential non-invasive predictors for electroanatomical remodeling of atrium in patients with nonvalvular atrial fibrillation. Circulation Journal, 75(3), 57–64.

    Article  Google Scholar 

  11. Yang, L., Xiufen, O., Shuqin, S., Yang, Y., Ying, S., Yanwei, Y., et al. (2011). Asymmetric dimethylarginine concentration and recurrence of atrial tachyarrhythmias after catheter ablation in patients with persistent atrial fibrillation. Journal of Interventional Cardiac Electrophysiology, 32(2), 147–154.

    Article  PubMed  Google Scholar 

  12. Shimano, M., Shibata, R., Tsuji, Y., Kamiya, H., Uchikawa, T., Harata, S., et al. (2008). Circulating adiponectin levels in patients with atrial fibrillation. Circulation Journal, 72(7), 1120–1124.

    Article  CAS  PubMed  Google Scholar 

  13. Reant, P., Lafitte, S., Jaïs, P., Serri, K., Weerasooriya, R., Hocini, M., et al. (2005). Reverse remodeling of the left cardiac chambers after catheter ablation after 1 year in a series of patients with isolated atrial fibrillation. Circulation, 112(19), 2896–2903.

    PubMed  Google Scholar 

  14. Tops, L. F., Bax, J. J., Zeppenfeld, K., Jongbloed, M. R., van der Wall, E. E., & Schalij, M. J. (2006). Effect of radiofrequency catheter ablation for atrial fibrillation on left atrial cavity size. American Journal of Cardiology, 97(8), 1220–1222.

    Article  PubMed  Google Scholar 

  15. Shelton, R. J., Clark, A. L., Goode, K., Rigby, A. S., & Cleland, J. G. (2006). The diagnostic utility of N-terminal pro-B-type natriuretic peptide for the detection of major structural heart disease in patients with atrial fibrillation. European Heart Journal, 27(19), 2353–2361.

    Article  CAS  PubMed  Google Scholar 

  16. Yamada, T., Murakami, Y., Okada, T., Yoshida, N., Toyama, J., Yoshida, Y., et al. (2007). Plasma brain natriuretic peptide level after radiofrequency catheter ablation of paroxysmal, persistent, and permanent atrial fibrillation. Europace, 9(9), 770–774.

    Article  PubMed  Google Scholar 

  17. Fujimoto, N., Mouri, N., Iwata, K., Ohuchi, E., Okada, Y., & Hayakawa, T. (1993). A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 2 (72-kDa gelatinase/type IV collagenase) using monoclonal antibodies. Clinica Chimica Acta, 221(1–2), 91–103.

    Article  CAS  Google Scholar 

  18. Fujimoto, N., Zhang, J., Iwata, K., Shinya, T., Okada, Y., & Hayakawa, T. (1993). A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases-2 using monoclonal antibodies. Clinica Chimica Acta, 220(1), 31–45.

    Article  CAS  Google Scholar 

  19. Pfeiffer, A., Middelberg-Bisping, K., Drewes, C., & Schatz, H. (1996). Elevated plasma levels of transforming growth factor-beta 1 in NIDDM. Diabetes Care, 19(10), 1113–1117.

    Article  CAS  PubMed  Google Scholar 

  20. Marcovecchio, M. L., Widmer, B., Dunger, D. B., & Dalton, R. N. (2008). Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with type 1 diabetes. Clinical Science (London), 115(12), 361–369.

    Article  CAS  Google Scholar 

  21. Lin, Y. J., Tsao, H. M., Chang, S. L., Lo, L. W., Tuan, T. C., Hu, Y. F., et al. (2010). Prognostic implications of the high-sensitive C-reactive protein in the catheter ablation of atrial fibrillation. American Journal of Cardiology, 105(4), 495–501.

    Article  CAS  PubMed  Google Scholar 

  22. Fan, J., Cao, H., Su, L., Ling, Z., Liu, Z., Lan, X., et al. (2012). NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial fibrillation in patients undergoing pulmonary vein isolation. Journal of Interventional Cardiac Electrophysiology, 33(1), 93–100.

    Article  PubMed  Google Scholar 

  23. Stefan, N., Vozarova, B., Funahashi, T., Matsuzawa, Y., Weyer, C., Lindsay, R. S., et al. (2002). Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes, 51(6), 1884–1888.

    Article  CAS  PubMed  Google Scholar 

  24. Markus, C. S., Fahim, A., James, W. C., Cindy, L., Tracey, L. M., John, P. C., et al. (2002). Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA, 287(11), 1420–1426.

    Article  Google Scholar 

  25. Creemers, E. E., Cleutjens, J. P., Smits, J. F., & Daemen, M. J. (2001). Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure? Circulation Research, 89(3), 201–210.

    Article  CAS  PubMed  Google Scholar 

  26. Webb, C. S., Bonnema, D. D., Ahmed, S. H., Leonardi, A. H., McClure, C. D., Clark, L. L., et al. (2006). Specific temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction: relation to left ventricular remodeling. Circulation, 114(10), 1020–1027.

    Article  CAS  PubMed  Google Scholar 

  27. Kaden, J. J., Dempfle, C. E., Sueselbeck, T., Brueckmann, M., Poerner, T. C., Haghi, D., et al. (2003). Time-dependent changes in the plasma concentration of matrix metalloproteinase 9 after acute myocardial infarction. Cardiology, 99(3), 140–144.

    Article  CAS  PubMed  Google Scholar 

  28. Brueckmann, M., Wolpert, C., Bertsch, T., Sueselbeck, T., Liebetrau, C., Kaden, J. J., et al. (2004). Markers of myocardial damage, tissue healing, and inflammation after radiofrequency catheter ablation of atrial tachyarrhythmias. Journal of Cardiovascular Electrophysiology, 15(6), 686–691.

    Article  PubMed  Google Scholar 

  29. Lijnen, P. J., Petrov, V. V., & Fagard, R. H. (2000). Induction of cardiac fibrosis by transforming growth factor-beta (1). Molecular Genetics and Metabolism, 71, 418–435.

    Article  CAS  PubMed  Google Scholar 

  30. Arujuna, A., Karim, R., Caulfield, D., Knowles, B., Rhode, K., Schaeffter, T., et al. (2012). Acute pulmonary vein isolation is achieved by a combination of reversible and irreversible atrial injury after catheter ablation: evidence from magnetic resonance imaging. Circulation Arrhythmia and Electrophysiology, 5(4), 691–700.

    Article  PubMed  Google Scholar 

  31. Teh, A. W., Kistler, P. M., Lee, G., Medi, C., Heck, P. M., Spence, S. J., et al. (2012). Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation. Heart Rhythm, 9(4), 473–480.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan

    Naoko Sasaki, Yasuo Okumura, Ichiro Watanabe, Hiroaki Mano, Koichi Nagashima, Kazumasa Sonoda, Rikitake Kogawa, Kimie Ohkubo, Toshiko Nakai & Atsushi Hirayama

Authors
  1. Naoko Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuo Okumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ichiro Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroaki Mano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Koichi Nagashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazumasa Sonoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rikitake Kogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kimie Ohkubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Toshiko Nakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Atsushi Hirayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuo Okumura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sasaki, N., Okumura, Y., Watanabe, I. et al. Increased levels of inflammatory and extracellular matrix turnover biomarkers persist despite reverse atrial structural remodeling during the first year after atrial fibrillation ablation. J Interv Card Electrophysiol 39, 241–249 (2014). https://doi.org/10.1007/s10840-013-9867-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-013-9867-6

Keywords

Search

Navigation