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The sympathetic nervous system in heart failure revisited

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Abstract

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.

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F.T and A.X. had the idea for the article, A.B., T.K., D.M., and T.A. performed the literature search and data analysis, F.T., A.B., T.K., D.M., T.A., J.S., and A.X. drafted and/or critically revised the work.

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Correspondence to Filippos Triposkiadis.

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Triposkiadis, F., Briasoulis, A., Kitai, T. et al. The sympathetic nervous system in heart failure revisited. Heart Fail Rev 29, 355–365 (2024). https://doi.org/10.1007/s10741-023-10345-y

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