title: The prognostic value of big endothelin-1 in more than 2,300 patients with heart failure enrolled in the Valsartan Heart Failure Trial (Val-HeFT).
abstract: BACKGROUND
  Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure.
  
  
  RESULTS
  Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP.
  
  
  CONCLUSIONS
  In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.
authors.affiliation: Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.forename: Simona
authors.initials: S
authors.lastname: Barlera
authors.forename: Dianne
authors.initials: D
authors.lastname: Judd
authors.forename: Monica
authors.initials: M
authors.lastname: Salio
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Perini
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Jay N
authors.initials: JN
authors.lastname: Cohn
mesh_terms: D000368:Aged; D002303:Cardiac Output, Low / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D002908:Chronic Disease; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009994:Osmolar Concentration; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
chemical_list: D019332:Endothelin-1; D020097:Natriuretic Peptide, Brain