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


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.


CONCLUSIONS
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.
Foley
Paul W X
PW
Department of Cardiology, University of Birmingham, Good Hope Hospital, Heart of England NHS Trust, Rectory Road, Sutton Coldfield, West Midlands, UK.
Stegemann
Berthold
B
Ng
Kelvin
K
Ramachandran
Sud
S
Proudler
Anthony
A
Frenneaux
Michael P
MP
Ng
Leong L
LL
Leyva
Francisco
F
D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D002304:Cardiac Pacing, Artificial / Q000401:mortality*; D017147:Defibrillators, Implantable; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D012307:Risk Factors; D016019:Survival Analysis
D015415:Biomarkers; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain