title: Prevention of liver cancer cachexia-induced cardiac wasting and heart failure.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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 β-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.
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
authors.forename: Anika
authors.initials: A
authors.lastname: Tschirner
authors.forename: Arash
authors.initials: A
authors.lastname: Haghikia
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Hind
authors.initials: H
authors.lastname: Lal
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Grzesiak
authors.forename: Elena
authors.initials: E
authors.lastname: Kaschina
authors.forename: Sandra
authors.initials: S
authors.lastname: Palus
authors.forename: Mareike
authors.initials: M
authors.lastname: Pötsch
authors.forename: Karoline
authors.initials: K
authors.lastname: von Websky
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
authors.forename: Celine
authors.initials: C
authors.lastname: Latouche
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: John
authors.initials: J
authors.lastname: Beadle
authors.forename: Josep M
authors.initials: JM
authors.lastname: Argiles
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.forename: Gabor
authors.initials: G
authors.lastname: Földes
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Thomas
authors.initials: T
authors.lastname: Force
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000517:prevention & control*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006333:Heart Failure / Q000517:prevention & control*; D048289:Imidazolidines / Q000494:pharmacology; D008113:Liver Neoplasms / Q000517:prevention & control*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D019282:Wasting Syndrome / Q000517:prevention & control*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D048289:Imidazolidines; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; C065166:imidapril; D038362:Glycogen Synthase Kinase 3; D018995:Myosin Heavy Chains; D017298:Bisoprolol
keywords: Cancer cachexia; Cardiac wasting; Heart failure; Intervention; Survival