Abstract
The immune system is intimately involved in the pathophysiology of heart failure. However, it is currently underused as a therapeutic target in the clinical setting. Moreover, the development of novel immunomodulatory therapies and their investigation for the treatment of patients with heart failure are hampered by the fact that currently used, evidence-based treatments for heart failure exert multiple immunomodulatory effects. In this Review, we discuss current knowledge on how evidence-based treatments for heart failure affect the immune system in addition to their primary mechanism of action, both to inform practising physicians about these pleiotropic actions and to create a framework for the development and application of future immunomodulatory therapies. We also delineate which subpopulations of patients with heart failure might benefit from immunomodulatory treatments. Furthermore, we summarize completed and ongoing clinical trials that assess immunomodulatory treatments in heart failure and present several therapeutic targets that could be investigated in the future. Lastly, we provide future directions to leverage the immunomodulatory potential of existing treatments and to foster the investigation of novel immunomodulatory therapeutics.
Key points
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Immune activation is intimately involved in the pathophysiology of heart failure.
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Immunomodulation is an underused therapeutic approach for the treatment of patients with heart failure.
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All current evidence-based treatments for heart failure can modulate immune activation in diverse ways, which has important clinical and therapeutic implications.
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The development of novel immunomodulatory interventions for the treatment of heart failure should take the immunomodulatory effects of existing treatments into account.
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Future developments in immunomodulation for heart failure should investigate both the optimization of immunomodulatory effects of current treatments and the potential benefits that can be derived by novel treatments.
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Markousis-Mavrogenis, G., Baumhove, L., Al-Mubarak, A.A. et al. Immunomodulation and immunopharmacology in heart failure. Nat Rev Cardiol 21, 119–149 (2024). https://doi.org/10.1038/s41569-023-00919-6
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DOI: https://doi.org/10.1038/s41569-023-00919-6
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