title: Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction.
abstract: Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10 years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1 year, median 371 days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD = 1.5, 95% confidence interval 1.1 to 2.1, p = 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD = 1.8, 95% confidence interval 1.2 to 2.6, p = 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p = 0.016). HGF showed a complementary value over NT-proBNP (p = 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP.
authors.affiliation: Servicio de Medicina Interna, Facultad de Medicina, Instituto de Investigación Sanitaria de Aragón, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain. Electronic address: jiperez@unizar.es.
authors.forename: Juan-Ignacio
authors.initials: JI
authors.lastname: Pérez-Calvo
authors.affiliation: Servicio de Medicina Interna, Hospital Universitario "Arnau de Villanova", Lleida, Spain.
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Morales-Rull
authors.affiliation: Servicio de Endocrinología y Metabolismo, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Gimeno-Orna
authors.affiliation: Laboratorio de Inmunología, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Lasierra-Díaz
authors.affiliation: Servicio de Medicina Interna, Facultad de Medicina, Instituto de Investigación Sanitaria de Aragón, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Josa-Laorden
authors.affiliation: Laboratorio de Bioquímica Clínica, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain.
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Puente-Lanzarote
authors.affiliation: Serviço de Medicina Interna, Hospital CUF-Porto, Faculdade Medicina Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Bettencourt
authors.affiliation: Servicio de Cardiología, Hospital Universitario "Virgen de la Arrixaca", Facultad de Medicina, Murcia, Spain.
authors.forename: Domingo A
authors.initials: DA
authors.lastname: Pascual-Figal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013318:Stroke Volume
chemical_list: D015415:Biomarkers; C066855:HGF protein, human; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D017228:Hepatocyte Growth Factor