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 ratio 1SD [ 1.5, 95% confidence interval 1.1 to 2.1, p [ 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio 1SD [ 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. Ó 2016 Elsevier Inc. All rights reserved. (Am J Cardiol 2016;118:543e549) Hepatocyte growth factor (HGF) is a disulfide-linked heterodimeric molecule comprising a 69-kDa kringlecontaining a chain and a 34-kDa b chain. 1 The HGF system (HGF and its receptor c-Met) has been found in various tissues and integrates complex biologic processes. 2 HGF has been described as a potent mitogenic growth factor for hepatocytes thought to be liver specific but also reported to possess mitogenic, motogenic, morphogenic, and antiapoptotic activities in different cell types. 3e5 Binding of HGF to its receptor c-Met leads to the activation of a signal cascade whose ultimate in vivo effects include organ development, angiogenesis, and tissue regeneration. 6e8 Plasma concentrations of HGF are increased in response to the damage of the liver and kidney. 9e11 In the setting of cardiovascular diseases, an increase of HGF has been observed in hypertension, atherosclerosis, acute myocardial infarction, and chronic heart failure (HF). 12e15 In patients with advanced HF and depressed left ventricular ejection fraction (LVEF), HGF has been reported to be predictive of cardiovascular and all-cause mortality, es...
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