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Complement C3a predicts outcome in cardiac resynchronization therapy of heart failure

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Abstract

Background

The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT).

Methods

We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6 months after CRT implantation.

Results

CRT reduced the C3a [212.5 (148.2–283.6) vs. 153 (119.8–218.3) ng/mL, p < 0.0001] and the sC5b-9 levels [296.9 (234.2–358.8) vs. 255.1 (210.1–319.0) ng/mL, p = 0.0006], but not the total C3 levels [1.43 (1.26–1.61) vs. 1.38 (1.23–1.57) g/L, p = 0.57]. C3a predicted the 5-year mortality of the patients [C3a > 165 ng/mL hazard ratio = 4.21 (1.65–10.72), p = 0.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI = 0.71 (0.43–0.98), p < 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03–0.12), p = 0.0002].

Conclusions

In patients with CRT, elevated C3a levels increase the risk of mortality independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by reducing the complement activation.

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Acknowledgments

We are grateful to all patients who participated in our study and to the professional assistance background of Semmelweis University. This work was supported by the National Development Agency of Hungary (‘Semmelweis Egyetem Híd Projekt’ (TÁMOP-4.2.2-08/1/KMR-2008-0004), ‘Semmelweis Egyetem Magiszter Program’ (TÁMOP-4.2.2./B10/1.-210-0013), the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (GS, LG) and the Hungarian Scientific Research Fund (OTKA K 105555).

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    Authors and Affiliations

    1. Heart and Vascular Center, Semmelweis University, Városmajor utca 68, Budapest, 1122, Hungary

      Gábor Széplaki, András Mihály Boros, Szabolcs Szilágyi, István Osztheimer, Annamária Kosztin, Klaudia Vivien Nagy, Júlia Karády, Levente Molnár, Tamás Tahin, Endre Zima, László Gellér & Béla Merkely

    2. Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary

      Zsigmond Jenei & Zoltán Prohászka

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    1. Gábor Széplaki
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    Correspondence to Béla Merkely.

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    Responsible Editor: Andrew Roberts.

    G. Széplaki and A. M. Boros contributed equally to the work presented in the manuscript and both are regarded as first authors.

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    Széplaki, G., Boros, A.M., Szilágyi, S. et al. Complement C3a predicts outcome in cardiac resynchronization therapy of heart failure. Inflamm. Res. 65, 933–940 (2016). https://doi.org/10.1007/s00011-016-0976-4

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