Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

PW Foley; B Stegemann; K Ng; S Ramachandran; A Proudler; MP Frenneaux; LL Ng; F Leyva

doi:10.1093/eurheartj/ehp300

Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

PW Foley, B Stegemann, K Ng, S Ramachandran, A Proudler, MP Frenneaux, LL Ng, F Leyva

Research output: Contribution to journal › Article › peer-review

Abstract

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-β-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) χ2 = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55–5.26; LR χ2 = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91–17.5; LR χ2 = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR χ2 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.

Original language	English
Pages (from-to)	2749–2757
Journal	European Heart Journal
Volume	30
Issue number	22
DOIs	https://doi.org/10.1093/eurheartj/ehp300
Publication status	Published - Nov 2009

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The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
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10.1093/eurheartj/ehp300Licence: CC BY-NC 3.0

Growth differentiation factor-15 predicts mortality and morbidity
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org Supplementary data
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@article{528df77a5fed4a33b6e2876ee8d678fb,

title = "Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.",

abstract = "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-β-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) χ2 = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55–5.26; LR χ2 = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91–17.5; LR χ2 = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR χ2 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.",

author = "PW Foley and B Stegemann and K Ng and S Ramachandran and A Proudler and MP Frenneaux and LL Ng and F Leyva",

note = "The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org Supplementary data",

year = "2009",

month = nov,

doi = "10.1093/eurheartj/ehp300",

language = "English",

volume = "30",

pages = "2749–2757",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "22",

}

TY - JOUR

T1 - Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

AU - Foley, PW

AU - Stegemann, B

AU - Ng, K

AU - Ramachandran, S

AU - Proudler, A

AU - Frenneaux, MP

AU - Ng, LL

AU - Leyva, F

N1 - The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org Supplementary data

PY - 2009/11

Y1 - 2009/11

N2 - 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-β-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) χ2 = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55–5.26; LR χ2 = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91–17.5; LR χ2 = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR χ2 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.

AB - 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-β-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) χ2 = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55–5.26; LR χ2 = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91–17.5; LR χ2 = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR χ2 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.

UR - http://europepmc.org/abstract/med/19666898

UR - https://academic.oup.com/eurheartj/article/30/22/2749/478295

U2 - 10.1093/eurheartj/ehp300

DO - 10.1093/eurheartj/ehp300

M3 - Article

C2 - 19666898

SN - 0195-668X

VL - 30

SP - 2749

EP - 2757

JO - European Heart Journal

JF - European Heart Journal

IS - 22

ER -

Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

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