Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study.
BACKGROUND
Plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), of their N-terminal pro-peptides, of endothelin-1 (ET-1), and big endothelin-1 (big ET-1) have diagnostic and prognostic significance in congestive heart failure (CHF). However, their respective values as a predictor of survival remain controversial and have never been directly compared in severe CHF.


RESULTS
We analyzed, in 47 patients with severe CHF (New York Heart Association [NYHA] class III to IV; age 66 +/- 8 years, ejection fraction 20 +/- 6%), the prognostic performance of a panel of neurohormones and assays (N-terminal pro-ANP 1-25, 68-98 by radioimmunoassay [RIA], and 1-98 by enzyme-linked immunosorbent assay [ELISA], BNP by RIA and immunoradiometric assay [IRMA], N-terminal pro-BNP by Elisa, ET-1 by RIA, and big ET-1 by RIA and Elisa. Data were compared with 40 patients with mild to moderate CHF [NYHA I-II] and 30 healthy subjects. After a follow-up of 81 +/- 15 months, there were 34 deaths and 1 heart transplant. All neurohormones were significantly higher at baseline in patients with severe than in mild to moderate CHF or healthy subjects (all P < .001). Although all neurohormones but BNP IRMA were significant predictors of survival in univariate analysis, only big ET-1 RIA and ET-1 were independent predictors of survival (improvement chi(2): 7.5 and 4.6, P < .01 and P < .05). Using medians as cutpoints of big ET-1 RIA and ET-1, 2 severe CHF populations were defined with a different outcome (5-year survival: 55 versus 18%, P < .01).


CONCLUSIONS
Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.
Van Beneden
Ronald
R
Diabetes and Nutrition Unit, Division of Cardiology, School of Public Health, University of Louvain, B-1200 Brussels, Belgium.
Gurné
Olivier
O
Selvais
Philippe L
PL
Ahn
Sylvie A
SA
Robert
Annie R
AR
Ketelslegers
Jean-Marie
JM
Pouleur
Hubert G
HG
Rousseau
Michel F
MF
D009320:Atrial Natriuretic Factor / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality*; D006801:Humans; D015592:Immunoradiometric Assay; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011379:Prognosis
D019332:Endothelin-1; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor