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Published in: Inflammation Research 12/2016

01-12-2016 | Original Research Paper

Complement C3a predicts outcome in cardiac resynchronization therapy of heart failure

Authors: Gábor Széplaki, András Mihály Boros, Szabolcs Szilágyi, István Osztheimer, Zsigmond Jenei, Annamária Kosztin, Klaudia Vivien Nagy, Júlia Karády, Levente Molnár, Tamás Tahin, Endre Zima, László Gellér, Zoltán Prohászka, Béla Merkely

Published in: Inflammation Research | Issue 12/2016

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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.
Literature
2.
go back to reference Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013;34(29):2281–329. doi:10.1093/eurheartj/eht150.CrossRefPubMed Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013;34(29):2281–329. doi:10.​1093/​eurheartj/​eht150.CrossRefPubMed
3.
go back to reference Dickstein K, Vardas PE, Auricchio A, Daubert JC, Linde C, McMurray J, et al. 2010 Focused Update of ESC guidelines on device therapy in heart failure: an update of the 2008 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J. 2010;31(21):2677–87. doi:10.1093/eurheartj/ehq337.CrossRefPubMed Dickstein K, Vardas PE, Auricchio A, Daubert JC, Linde C, McMurray J, et al. 2010 Focused Update of ESC guidelines on device therapy in heart failure: an update of the 2008 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J. 2010;31(21):2677–87. doi:10.​1093/​eurheartj/​ehq337.CrossRefPubMed
8.
go back to reference Oksjoki R, Kovanen PT, Meri S, Pentikainen MO. Function and regulation of the complement system in cardiovascular diseases. Front Biosci J Virtual Libr. 2007;12:4696–708.CrossRef Oksjoki R, Kovanen PT, Meri S, Pentikainen MO. Function and regulation of the complement system in cardiovascular diseases. Front Biosci J Virtual Libr. 2007;12:4696–708.CrossRef
10.
go back to reference Gombos T, Forhecz Z, Pozsonyi Z, Szeplaki G, Kunde J, Fust G, et al. Complement anaphylatoxin C3a as a novel independent prognostic marker in heart failure. Clin Res Cardiol Off J Ger Card Soc. 2012;101(8):607–15. doi:10.1007/s00392-012-0432-6.CrossRef Gombos T, Forhecz Z, Pozsonyi Z, Szeplaki G, Kunde J, Fust G, et al. Complement anaphylatoxin C3a as a novel independent prognostic marker in heart failure. Clin Res Cardiol Off J Ger Card Soc. 2012;101(8):607–15. doi:10.​1007/​s00392-012-0432-6.CrossRef
12.
go back to reference Aukrust P, Gullestad L, Lappegard KT, Ueland T, Aass H, Wikeby L, et al. Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment. Circulation. 2001;104(13):1494–500.CrossRefPubMed Aukrust P, Gullestad L, Lappegard KT, Ueland T, Aass H, Wikeby L, et al. Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment. Circulation. 2001;104(13):1494–500.CrossRefPubMed
14.
go back to reference Boros AM, Szeplaki G, Perge P, Jenei Z, Bagyura Z, Zima E, et al. The ratio of the neutrophil leucocytes to the lymphocytes predicts the outcome after cardiac resynchronization therapy. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol. 2015. doi:10.1093/europace/euv100. Boros AM, Szeplaki G, Perge P, Jenei Z, Bagyura Z, Zima E, et al. The ratio of the neutrophil leucocytes to the lymphocytes predicts the outcome after cardiac resynchronization therapy. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol. 2015. doi:10.​1093/​europace/​euv100.
15.
go back to reference Boros AM, Perge P, Jenei Z, Karady J, Zima E, Molnar L, et al. Measurement of the red blood cell distribution width improves the risk prediction in cardiac resynchronization therapy. Dis Mark. 2016;2016:7304538. doi:10.1155/2016/7304538. Boros AM, Perge P, Jenei Z, Karady J, Zima E, Molnar L, et al. Measurement of the red blood cell distribution width improves the risk prediction in cardiac resynchronization therapy. Dis Mark. 2016;2016:7304538. doi:10.​1155/​2016/​7304538.
17.
go back to reference Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology (Cambridge, Mass). 2010;21(1):128–38. doi:10.1097/EDE.0b013e3181c30fb2.CrossRef Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology (Cambridge, Mass). 2010;21(1):128–38. doi:10.​1097/​EDE.​0b013e3181c30fb2​.CrossRef
21.
go back to reference Michelucci A, Ricciardi G, Sofi F, Gori AM, Pirolo F, Pieragnoli P, et al. Relation of inflammatory status to major adverse cardiac events and reverse remodeling in patients undergoing cardiac resynchronization therapy. J Card Fail. 2007;13(3):207–10. doi:10.1016/j.cardfail.2006.11.013.CrossRefPubMed Michelucci A, Ricciardi G, Sofi F, Gori AM, Pirolo F, Pieragnoli P, et al. Relation of inflammatory status to major adverse cardiac events and reverse remodeling in patients undergoing cardiac resynchronization therapy. J Card Fail. 2007;13(3):207–10. doi:10.​1016/​j.​cardfail.​2006.​11.​013.CrossRefPubMed
22.
go back to reference Linde C, Mealing S, Hawkins N, Eaton J, Brown B, Daubert JC. Cost-effectiveness of cardiac resynchronization therapy in patients with asymptomatic to mild heart failure: insights from the European cohort of the REVERSE (Resynchronization Reverses remodeling in Systolic Left Ventricular Dysfunction). Eur Heart J. 2011;32(13):1631–9. doi:10.1093/eurheartj/ehq408.CrossRefPubMed Linde C, Mealing S, Hawkins N, Eaton J, Brown B, Daubert JC. Cost-effectiveness of cardiac resynchronization therapy in patients with asymptomatic to mild heart failure: insights from the European cohort of the REVERSE (Resynchronization Reverses remodeling in Systolic Left Ventricular Dysfunction). Eur Heart J. 2011;32(13):1631–9. doi:10.​1093/​eurheartj/​ehq408.CrossRefPubMed
Metadata
Title
Complement C3a predicts outcome in cardiac resynchronization therapy of heart failure
Authors
Gábor Széplaki
András Mihály Boros
Szabolcs Szilágyi
István Osztheimer
Zsigmond Jenei
Annamária Kosztin
Klaudia Vivien Nagy
Júlia Karády
Levente Molnár
Tamás Tahin
Endre Zima
László Gellér
Zoltán Prohászka
Béla Merkely
Publication date
01-12-2016
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 12/2016
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-016-0976-4

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