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Original article
Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure
  1. Kathrin Rychli1,
  2. Bernhard Richter1,
  3. Philipp J Hohensinner1,
  4. Kariem Mahdy Ali1,
  5. Stephanie Neuhold1,
  6. Gerlinde Zorn1,
  7. Rudolf Berger1,
  8. Deddo Mörtl1,
  9. Kurt Huber2,
  10. Richard Pacher1,
  11. Johann Wojta1,
  12. Alexander Niessner1,
  13. Martin Hülsmann1
  1. 1Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
  2. 2Department of Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria
  1. Correspondence to Alexander Niessner, Department of Internal Medicine II, Division of Cardiology, Waehringer Guertel 18-20, 1090 Vienna, Austria; alexander.niessner{at}meduniwien.ac.at

Abstract

Objective To assess the prognostic value of the mitogenic, antiapoptotic, angiogenic and antifibrotic hepatocyte growth factor (HGF) in heart failure (HF).

Design Prospective cohort study.

Setting/patients Assessment of HGF levels at inclusion in 351 patients with advanced HF (median 75 years, interquartile range (IQR) 63–82, 66% male).

Main outcome measures All-cause mortality, cardiovascular mortality.

Results During a median follow-up of 16 months, 26% of patients died. HGF tertiles were associated with an increasing risk for all-cause mortality (p<0.001) with a hazard ratio (HR) of 3.06 (95% confidence interval (CI) 1.69 to 5.53) for the third compared with the first tertile. This association remained significant after multivariable adjustment for B-type natriuretic peptide (BNP) and other risk factors (p=0.002). Subgroup analysis revealed that HGF was a strong predictor of the secondary end point cardiovascular mortality in ischaemic HF (p=0.009) with an adjusted HR of 6.2 (95% CI 1.76 to 21.8) comparing the third with the first tertile but not in non-ischaemic HF (HR=1.47, 95% CI 0.48 to 4.49, p=0.5). Patients with high HGF but low BNP had a comparable survival rate to those with elevated BNP but low HGF (p=0.66). Of note, the dose of angiotensin converting enzyme (ACE) inhibitors inversely correlated with HGF concentrations (r=−0.25, p<0.001).

Conclusions HGF is a strong and independent predictor of mortality in advanced HF and, in particular, in ischaemic HF. These results indicate that HGF with its multiple effects on myocardial function exerts an overall deleterious effect in advanced HF. HGF may be of special interest for risk prediction and tailoring of HF treatment.

  • Hepatocyte growth factor
  • angiogenesis
  • heart failure
  • cardiomyopathy
  • prognosis
  • cardiac remodelling
  • left ventricular hypertrophy
  • aortic valve disease
  • gene expression

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Footnotes

  • KR and BR contributed equally to this study.

  • Funding This work was supported by the Association for the Promotion of Research in Arteriosclerosis, Thrombosis and Vascular Biology (Vienna, Austria) and by the Ludwig Boltzmann Foundation for Cardiovascular Research (Vienna, Austria).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was approved by the ethics committee of the Medical University of Vienna, Austria.

  • Provenance and peer review Not commissioned; externally peer reviewed.