Prevention of liver cancer cachexia-induced cardiac wasting and heart failure

Jochen Springer, Anika Tschirner, Arash Haghikia, Stephan von Haehling, Hind Lal, Aleksandra Grzesiak, Elena Kaschina, Sandra Palus, Mareike S Potsch, Karoline von Websky, Berthold Hocher, Celine Latouche, Frederic Jaisser, Lars Morawietz, Andrew Justin Stewart Coats, John Beadle, Josep M Argiles, Thomas Thum, Gabor Foldes, Wolfram DoehnerDenise Hilfiker-Kleiner, Thomas Force, Stefan D Anker

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    Abstract

    Aims Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Methods and results Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Conclusion Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the ?-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer
    Original languageEnglish
    Pages (from-to)932 - 941
    Number of pages10
    JournalEuropean Heart Journal
    Volume35
    Issue number14
    DOIs
    Publication statusPublished - 2014

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