Giuseppe Rengo1, Gennaro Pagano2, Valentina Parisi2, Grazia Daniela Femminella2, Claudio de Lucia2, Daniela Liccardo2, Alessandro Cannavo3, Carmela Zincarelli4, Klara Komici2, Stefania Paolillo5, Flavia Fusco5, Walter J Koch6, Pasquale Perrone Filardi5, Nicola Ferrara1, Dario Leosco7. 1. 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. 2. Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy. 3. Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy; Center of Translational Medicine, Temple University, Philadelphia, PA, USA. 4. Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme (BN), Italy. 5. Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy. 6. Center of Translational Medicine, Temple University, Philadelphia, PA, USA. 7. Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Italy. Electronic address: dleosco@unina.it.
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. METHODS AND 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.
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. METHODS AND 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.