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  • Review Article
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Reappraising the role of inflammation in heart failure

Nature Reviews Cardiology volume 17, pages 269–285 (2020)Cite this article

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A Publisher Correction to this article was published on 12 March 2021

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Abstract

The observation that heart failure with reduced ejection fraction is associated with elevated circulating levels of pro-inflammatory cytokines opened a new area of research that has revealed a potentially important role for the immune system in the pathogenesis of heart failure. However, until the publication in 2019 of the CANTOS trial findings on heart failure outcomes, all attempts to target inflammation in the heart failure setting in phase III clinical trials resulted in neutral effects or worsening of clinical outcomes. This lack of positive results in turn prompted questions on whether inflammation is a cause or consequence of heart failure. This Review summarizes the latest developments in our understanding of the role of the innate and adaptive immune systems in the pathogenesis of heart failure, and highlights the results of phase III clinical trials of therapies targeting inflammatory processes in the heart failure setting, such as anti-inflammatory and immunomodulatory strategies. The most recent of these studies, the CANTOS trial, raises the exciting possibility that, in the foreseeable future, we might be able to identify those patients with heart failure who have a cardio-inflammatory phenotype and will thus benefit from therapies targeting inflammation.

Key points

  • Patients with heart failure with reduced ejection fraction have elevated circulating levels of pro-inflammatory cytokines compared with healthy individuals.

  • The innate and adaptive immune systems are activated in heart failure and comprise non-cellular and cellular components, including macrophages, mast cells, B cells and T cells.

  • The repertoire of immunological responses differs in acute and chronic myocardial inflammation.

  • Initial phase III clinical trials targeting inflammation in the setting of heart failure had neutral results.

  • In the CANTOS trial, targeted anti-cytokine therapy with a monoclonal antibody against IL-1β resulted in improved heart failure outcomes in patients with myocardial infarction with or without established heart failure.

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Fig. 1: The innate and adaptive immune systems in cardiac disease.
Fig. 2: Para-inflammation and chronic myocardial inflammation.
Fig. 3: Beneficial and deleterious effects of para-inflammation.

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Acknowledgements

We apologize in advance to colleagues whose work was not directly cited in this Review because of the imposed space limitations. The authors receive support research funds from the NIH (R01 HL58081, HL-73017, HL089543, NIH T32 HL007081 and K08 HL1945108).

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Authors and Affiliations

  1. Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Luigi Adamo, Cibele Rocha-Resende & Douglas L. Mann

  2. Division of Cardiovascular Disease and Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Sumanth D. Prabhu

  3. Medical Service, Birmingham VA Medical Center, Birmingham, AL, USA

    Sumanth D. Prabhu

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  1. Luigi Adamo
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L.A., S.D.P., C.R.R. and D.L.M. researched data for article and wrote the manuscript. All authors provided substantial contribution to discussion of content and reviewed and/or edited the manuscript before submission.

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Correspondence to Douglas L. Mann.

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Competing interests

L.A. and D.L.M. are co-founders of iCordis, a start-up company focused on developing B cell modulating therapies for the prevention and treatment of heart failure. The other authors declare no competing interests.

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Nature Reviews Cardiology thanks P. Alcaide, C. Tschöpe and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Adamo, L., Rocha-Resende, C., Prabhu, S.D. et al. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol 17, 269–285 (2020). https://doi.org/10.1038/s41569-019-0315-x

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