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  • Review Article
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Neurohormonal activation in heart failure with reduced ejection fraction

Nature Reviews Cardiology volume 14, pages 30–38 (2017)Cite this article

Subjects

Key Points

  • Heart failure with reduced ejection fraction (HFrEF) is initiated when an 'index event' causes the pumping capacity of the heart to be impaired

  • Reduced pumping capacity of the heart results in compensatory activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system, which together is referred to as 'neurohormonal activation'

  • Neurohormonal activation results in a series of coordinated responses that collectively work to restore cardiovascular homeostasis in the short term

  • Sustained neurohormonal activation drives the progression of HFrEF through the deleterious effects exerted on the circulation and the myocardium

  • Antagonism of neurohormonal systems forms the basis of modern therapy for HFrEF

Abstract

Heart failure with reduced ejection fraction (HFrEF) develops when cardiac output falls as a result of cardiac injury. The most well-recognized of the compensatory homeostatic responses to a fall in cardiac output are activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS). In the short term, these 'neurohormonal' systems induce a number of changes in the heart, kidneys, and vasculature that are designed to maintain cardiovascular homeostasis. However, with chronic activation, these responses result in haemodynamic stress and exert deleterious effects on the heart and the circulation. Neurohormonal activation is now known to be one of the most important mechanisms underlying the progression of heart failure, and therapeutic antagonism of neurohormonal systems has become the cornerstone of contemporary pharmacotherapy for heart failure. In this Review, we discuss the effects of neurohormonal activation in HFrEF and highlight the mechanisms by which these systems contribute to disease progression.

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Figure 1: Activation of neurohormonal systems in heart failure.
Figure 2: Effects of sympathetic nervous system activation.
Figure 3: Cardiac and cellular remodelling in response to haemodynamic overloading.

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Acknowledgements

The authors' research is supported by research funds from the NIH (R01 HL58081, RO1 111094, T32 HL007081).

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  1. Division of Cardiology, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    Justin Hartupee & Douglas L. Mann

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Both authors researched data for the article, discussed its content, wrote the manuscript, and reviewed/edited it before submission.

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Correspondence to Douglas L. Mann.

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D.L.M. is a consultant to Novartis and is on the steering committee for the PARADISE trial. J.H. declares no competing interests.

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Hartupee, J., Mann, D. Neurohormonal activation in heart failure with reduced ejection fraction. Nat Rev Cardiol 14, 30–38 (2017). https://doi.org/10.1038/nrcardio.2016.163

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