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

2.50
Hdl Handle:
http://hdl.handle.net/10547/593456
Title:
Prevention of liver cancer cachexia-induced cardiac wasting and heart failure
Authors:
Springer, Jochen; Tschirner, Anika; Haghikia, Arash; von Haehling, Stephan; Lal, Hind; Grzesiak, Aleksandra; Kaschina, Elena; Palus, Sandra; Pötsch, Maeike; von Websky, Karoline; Hocher, Berthold; Latouche, Celine; Jaisser, Frederic; Morawietz, Lars; Coats, Andrew J.S.; Beadle, John; Argiles, Josep M.; Thum, Thomas; Földes, Gabor; Doehner, Wolfram; Hilfiker-Kleiner, Denise; Force, Thomas; Anker, Stefan D.
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 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.
Citation:
Springer, J. et al (2013) 'Prevention of liver cancer cachexia-induced cardiac wasting and heart failure' European heart journal 35(14):932-41
Publisher:
Oxford University Press
Journal:
European heart journal
Issue Date:
29-Aug-2013
URI:
http://hdl.handle.net/10547/593456
DOI:
dx.doi.org/10.1093/eurheartj/eht302
PubMed ID:
23990596
PubMed Central ID:
PMC3977133
Additional Links:
http://eurheartj.oxfordjournals.org/content/35/14/932
Type:
Article
Language:
en
ISSN:
0195-668x
EISSN:
1522-9645
Appears in Collections:
IHR Institute for Health Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSpringer, Jochenen
dc.contributor.authorTschirner, Anikaen
dc.contributor.authorHaghikia, Arashen
dc.contributor.authorvon Haehling, Stephanen
dc.contributor.authorLal, Hinden
dc.contributor.authorGrzesiak, Aleksandraen
dc.contributor.authorKaschina, Elenaen
dc.contributor.authorPalus, Sandraen
dc.contributor.authorPötsch, Maeikeen
dc.contributor.authorvon Websky, Karolineen
dc.contributor.authorHocher, Bertholden
dc.contributor.authorLatouche, Celineen
dc.contributor.authorJaisser, Fredericen
dc.contributor.authorMorawietz, Larsen
dc.contributor.authorCoats, Andrew J.S.en
dc.contributor.authorBeadle, Johnen
dc.contributor.authorArgiles, Josep M.en
dc.contributor.authorThum, Thomasen
dc.contributor.authorFöldes, Gaboren
dc.contributor.authorDoehner, Wolframen
dc.contributor.authorHilfiker-Kleiner, Deniseen
dc.contributor.authorForce, Thomasen
dc.contributor.authorAnker, Stefan D.en
dc.date.accessioned2016-01-14T13:56:48Zen
dc.date.available2016-01-14T13:56:48Zen
dc.date.issued2013-08-29en
dc.identifier.citationSpringer, J. et al (2013) 'Prevention of liver cancer cachexia-induced cardiac wasting and heart failure' European heart journal 35(14):932-41en
dc.identifier.issn0195-668xen
dc.identifier.pmid23990596en
dc.identifier.doidx.doi.org/10.1093/eurheartj/eht302en
dc.identifier.urihttp://hdl.handle.net/10547/593456en
dc.description.abstractAims 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 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.en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urlhttp://eurheartj.oxfordjournals.org/content/35/14/932en
dc.subjectcancer cachexiaen
dc.subjectheart failureen
dc.subjectcardiac wastingen
dc.subjectsurvivalen
dc.subjectinterventionen
dc.titlePrevention of liver cancer cachexia-induced cardiac wasting and heart failureen
dc.typeArticleen
dc.identifier.eissn1522-9645en
dc.identifier.journalEuropean heart journalen
dc.identifier.pmcidPMC3977133en

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