title: Prognostic Value and Kinetics of Soluble Neprilysin in Acute Heart Failure: A Pilot Study.
abstract: OBJECTIVE
  This study sought to examine the prognostic value of the soluble form of neprilysin (sNEP) in acute heart failure (AHF) and sNEP kinetics during hospital admission.
  
  
  BACKGROUND
  sNEP was recently identified in chronic heart failure (HF) and was associated with cardiovascular outcomes.
  
  
  METHODS
  A total of 350 patients (53% women, mean 72.6 ± 10.7 years of age) were included in the study. Primary endpoints were composites of cardiovascular death or HF hospitalizations at short-term (2 months) and long-term (mean: 1.8 ± 1.2 years) follow-up. sNEP was measured using an ad hoc-modified enzyme-linked immunosorbent assay, and its prognostic value was assessed using Cox regression analyses. In a subgroup of patients, sNEP was measured both at admission and at discharge (n = 92).
  
  
  RESULTS
  Median admission sNEP concentrations were 0.67 ng/ml (Q1 to Q3: 0.37 to 1.29), and sNEP was significantly associated, in age-adjusted Cox regression analyses, with the composite endpoint at short-term (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.04 to 1.61; p = 0.02) and long-term (HR: 1.23; 95% CI: 1.01 to 1.05; p = 0.003) follow-up. In multivariate Cox analyses that included clinical variables and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration, sNEP concentration at admission showed a clear trend toward significance for the composite endpoint at 2 months (HR: 1.22; 95% CI: 0.97 to 1.53; p = 0.09) and remained significant at the end of follow-up (HR: 1.21; 95% CI: 1.04 to 1.40; p = 0.01). At discharge, sNEP levels decreased from 0.70 to 0.52 ng/ml (p = 0.06).
  
  
  CONCLUSIONS
  Admission sNEP concentration was associated with short- and long-term outcomes in AHF, and dynamic sNEP concentrations were observed during hospital admission. These preliminary data may be hypothesis-generating for the use of NEP inhibitors in AHF.
authors.affiliation: Cardiology Service and Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain. Electronic address: abayesgenis@gmail.com.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayés-Genís
authors.affiliation: Biochemistry Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Barallat
authors.affiliation: Cardiology Department, Hospital Virgen de la Arrixaca, Department of Medicine, University of Murcia, Murcia, Spain.
authors.forename: Domingo
authors.initials: D
authors.lastname: Pascual-Figal
authors.affiliation: Cardiology Department, Hospital Virgen de la Arrixaca, Department of Medicine, University of Murcia, Murcia, Spain.
authors.forename: Domingo
authors.initials: D
authors.lastname: Pascual
authors.affiliation: Biochemistry Service, Hospital Clínico Universitario, Valencia, Spain; University of Valencia, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Nuñez
authors.affiliation: Cardiology Service, Hospital Clínico Universitario, Valencia, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Miñana
authors.affiliation: Cardiology Department, Hospital Virgen de la Arrixaca, Department of Medicine, University of Murcia, Murcia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Sánchez-Mas
authors.affiliation: Biochemistry Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Galan
authors.affiliation: University of Valencia, Valencia, Spain; Cardiology Service, Hospital de Manises, Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchis
authors.affiliation: Cardiology Service and Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Zamora
authors.affiliation: Cardiology Department, Hospital Virgen de la Arrixaca, Department of Medicine, University of Murcia, Murcia, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Pérez-Martínez
authors.affiliation: Cardiology Service and Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Lupón
mesh_terms: D015415:Biomarkers / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008297:Male; D015260:Neprilysin / Q000097:blood*; D010865:Pilot Projects; D011379:Prognosis; D012016:Reference Values
chemical_list: D015415:Biomarkers; D015260:Neprilysin
keywords: acute heart failure; neprilysin; prognosis