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The Control of Adrenergic Function in Heart Failure: Therapeutic Intervention

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Abstract

Chronic heart failure is characterised by excess adrenergic activity that augurs a poor prognosis. The reasons for increased adrenergic activity are complex and incompletely understood. The circumstantial evidence relating increased activity to adverse outcome is powerful, but not yet conclusive.

In normal subjects, autonomic control of the circulation is predominantly under the control of sympatho-inhibitory inputs from the arterial and cardiopulmonary baroreceptors, with a small input from the excitatory ergo- and chemo-receptors. In heart failure, the situation is reversed, with loss of the restraining input from the baroreceptors and an increase in the excitatory inputs, resulting in excessive adrenergic activity.

The circumstantial evidence linking neuroendocrine activation with poor outcome coupled with the clinical success of inhibition of the renin-angiotensin-aldosterone system has long suggested that inhibition of adrenergic activity might be beneficial in heart failure. There is a number of potential ways of achieving this. Improved treatment of heart failure itself may reduce sympathetic drive. There is an interplay between angiotensin II, aldosterone and the sympathetic nervous system, and thus RAAS antagonists, such as angiotensin converting enzyme inhibitors and spironolactone could directly reduce sympathetic activation. Exercise rehabilitation may similarly reduce sympathetic activity.

Recently, β-adrenergic receptor antagonists have been conclusively shown to improve symptoms, reduce hospitalisations and increase survival. However, the demonstration that central reduction of sympathetic activity with agents such as moxonidine increases morbidity and mortality suggests that we do not properly understand the role of sympathetic activation in the pathophysiology of heart failure.

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  1. Department of Cardiology, Castle Hill Hospital, Castle Road, Cottingham, Hull, HU16 5JQ

    Andrew L. Clark & John G.F. Cleland

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Clark, A.L., Cleland, J.G. The Control of Adrenergic Function in Heart Failure: Therapeutic Intervention. Heart Fail Rev 5, 101–114 (2000). https://doi.org/10.1023/A:1009854325711

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