title: Changes of plasma norepinephrine and serum N-terminal pro-brain natriuretic peptide after exercise training predict survival in patients with heart failure.
abstract: BACKGROUND
  Short-term changes of neurohormones can give important prognostic information in heart failure (HF) patients. In this study, we evaluate whether changes in plasma Norepinephrine (NE) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) after exercise training predict cardiac mortality in HF patients.
  
  
  RESULTS
  We enrolled 221 HF patients (mean age 72.5 ± 10.2 year) followed-up for a mean period of 27.64 ± 10.7 months. All pts underwent a 3-month exercise training. Before training, clinical examination, echocardiography, peak VO2 determination, and blood draw for NT-proBNP and NE measurements were performed. Primary end-point was cardiac related mortality. Eighty-six-nine percent of patients were in NYHA class III, mean left ventricular ejection fraction (LVEF) was 32.5 ± 10.4%, and mean peak VO2 was 12.36 ± 1.45 ml/kg/min. At baseline, mean NT-proBNP was 2111.4 ± 1145.6 pg/ml and mean NE was 641.8 ± 215.3 pg/ml. One hundred-one subjects died for cardiac causes. Training was associated with a significant increase of peak VO2 and LVEF, whereas NE, NT-proBNP, and heart rate decreased. Multiple Cox proportional hazards regression analysis was performed using delta% values (post vs pre-training) of LVEF, heart rate, NE, and NT-proBNP along with baseline covariates, revealing delta value of NE as the strongest predictor of cardiac mortality. Noteworthy, training reduced NT-proBNP in both survivor and non-survivor patients, while a lack of reduction of NE was observed in non survivors.
  
  
  CONCLUSIONS
  In our HF population, short-term changes of NE after exercise training independently predicted long-term cardiac mortality.
authors.affiliation: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme (BN), Italy; Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rengo
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pagano
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Parisi
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Grazia Daniela
authors.initials: GD
authors.lastname: Femminella
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: de Lucia
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Liccardo
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy; Center of Translational Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cannavo
authors.affiliation: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme (BN), Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Zincarelli
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Klara
authors.initials: K
authors.lastname: Komici
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolillo
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Fusco
authors.affiliation: Center of Translational Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone Filardi
authors.affiliation: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme (BN), Italy; Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferrara
authors.affiliation: Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy. Electronic address: dleosco@unina.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Leosco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009638:Norepinephrine / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009638:Norepinephrine
keywords: Exercise training; Heart failure; N-terminal pro-brain natriuretic peptide; Norepinephrine; Prognosis