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Chronic Heart Failure: The Roles of the Tumor Necrosis Factor-Alpha Axis and Left-Atrial Structural and Functional Remodeling Open Access


Other title
Cardiac remodeling
Cardiac MRI
Chronic heart failure
Plasma biomarkers
Type of item
Degree grantor
University of Alberta
Author or creator
Putko, Brendan N B
Supervisor and department
Oudit, Gavin (Medicine)
Examining committee member and department
Tsuyuki, Ross (Medicine)
Kaul, Padma (Medicine)
Keeling, Stephanie (Medicine)
McAlister, Finlay (Medicine)
Department of Medicine
Experimental Medicine
Date accepted
Graduation date
Master of Science
Degree level
Heart failure (HF) is a global epidemic, with a substantial burden on healthcare systems. Effective therapies have emerged for patients suffering from HF with reduced ejection fraction (HFREF), but not for those with preserved ejection fraction (HFPEF). Recently, systemic inflammation, driven by comorbid conditions, was attributed a larger role in the pathogenesis of HFPEF than HFREF. On the other hand, the role of the left atrium (LA) in HF remains unclear. Herein, the roles of inflammatory dysregulation and cardiac remodeling are explored in HF. The results presented suggest that dysregulation of the tumor necrosis factor-alpha axis may be a primary mediator of disease manifestations in HFPEF. The results show the LA plays variable role in in HF, whereby some patients rely on LA contraction for sufficient cardiac output. Altogether these findings contribute to a growing body of knowledge about the roles of inflammation and the LA in HF.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Putko BN, Wang Z, Lo J, Anderson T, Becher H, Dyck JR, Kassiri Z and Oudit GY (2014) Circulating levels of tumor necrosis factor-alpha receptor 2 are increased in heart failure with preserved ejection fraction relative to heart failure with reduced ejection fraction: evidence for a divergence in pathophysiology. PLoS One 9(6):e99495.

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