Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy..pdf (360.42 kB)
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Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy

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journal contribution
posted on 24.10.2012, 09:03 by P. W. X. Foley, F. Leyva, B. Stegemann, Kelvin Ng, Leong L. Ng, S. Ramachandran, A. Proudler, M. P. Frenneaux
AIMS: The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor-beta-related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. METHODS AND RESULTS: Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 +/- 11 years (mean +/- SD), left ventricular ejection fraction (LVEF) 23.1 +/- 9.8%, New York Class Association (NYHA) class III (n = 117) or IV (n = 41), and QRS 153.9 +/- 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P = 0.0049] and log NT pro-BNP (HR, 2.12; P = 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was -0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95% confidence interval (CI), 2.31-11.9; likelihood ratio (LR) chi(2) = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55-5.26; LR chi(2) = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91-17.5; LR chi(2) = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR chi(2) for all endpoints. CONCLUSION: Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.

Funding

Funding to pay the Open Access publication charges for this article was provided by the Cardiovascular Research Fund, Heart of England NHS Trust.

History

Citation

European Heart Journal, 2009, 30 (22), pp. 2749-2757

Published in

European Heart Journal

Publisher

Oxford University Press (OUP) for European Society of Cardiology

issn

0195-668X

eissn

1522-9645

Acceptance date

07/07/2009

Copyright date

2009

Available date

24/10/2012

Publisher version

http://eurheartj.oxfordjournals.org/content/30/22/2749

Language

en