Objective: Cathepsin B is a prominent lysosomal protease and is involved in apoptosis as well as degradation of myofibrillar proteins in myocardial infarction. The aim of this study was to investigate myocardial cathepsin B expression in failing and non-failing human hearts. Methods: Tissue samples were taken from transplanted left ventricles from 20 patients with dilated cardiomyopathy and 5 non-failing donor hearts that could not be transplanted for technical reasons. Myocardial cathepsin B expression was determined by immunohistochemistry, the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Apoptosis was assessed by TUNEL staining. Results: Positive cathepsin B staining was found in failing and non-failing hearts. The expression of cathepsin B at mRNA and protein levels was significantly higher in failing hearts compared with non-failing hearts. Correlation analysis revealed that cathepsin B at mRNA and protein levels negatively correlated with EF (r = 0.66, p = 0.002 and r = 0.492, p = 0.028, respectively) in patients with heart failure. The apoptotic index was 0.015 +/- 0.006 in failing hearts and 0.002 +/- 0.001 in non-failing hearts (p < 0.01). Conclusion: Increased myocardial expression of cathepsin B was found in patients with heart failure suggesting that cathepsin B might play a role in the genesis and development of heart failure. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.