title: Clinical significance of endogenous vasoactive neurohormones in chronic systolic heart failure.
abstract: BACKGROUND
  Neurohormonal activation is a pathophysiological hallmark of acute and chronic heart failure (HF). The clinical significance of more recently discovered endogenous vasoactive hormones has not been well-characterized.
  
  
  RESULTS
  In 154 subjects with stable, chronic systolic HF (New York Heart Association Class I-IV, left ventricular [LV] ejection fraction <or=40%), we measured plasma levels of urocortin 1 (UCN-1), urotensin II (UT-II), and endothelin-1 (ET-1) and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse clinical events (all-cause mortality, cardiac transplantation or HF hospitalization) were prospectively tracked for a median of 39 months. Plasma levels of UCN-1 and ET-1 (but not UT-II) increased with LV diastolic dysfunction stage, right ventricular systolic dysfunction class, and mitral regurgitation severity (P < .01 for all). Higher plasma levels of UCN-1 and ET-1 (but not UT-II) predicted increased risk for adverse clinical events. After adjustment for age, LV ejection fraction, and plasma amino-terminal pro-B-type natriuretic peptide, plasma UCN-1 >or=12.1 pM (HR: 2.02, 95% CI: 1.08-3.93, P = .029) and ET-1 >or=2.29 pM (HR: 2.52, 95% CI: 1.24-5.03, P = .011) remained significant independent risk factors for adverse clinical events.
  
  
  CONCLUSIONS
  Higher levels of plasma levels of UCN-1 and ET-1 but not UT-II were associated with worse LV diastolic performance and poorer long-term clinical outcomes in patients with chronic systolic HF.
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. tangw@ccf.org
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Kevin
authors.initials: K
authors.lastname: Shrestha
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Martin
authors.forename: Allen G
authors.initials: AG
authors.lastname: Borowski
authors.forename: Sue
authors.initials: S
authors.lastname: Jasper
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Yandle
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Allan L
authors.initials: AL
authors.lastname: Klein
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015331:Cohort Studies; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054832:Urocortins / Q000097:blood*
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; C426705:UCN2 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone