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Review
. 2023 Oct 12;12(20):6486.
doi: 10.3390/jcm12206486.

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF

Filippos Triposkiadis  1 , Alexandros Briasoulis  2 , Pantelis Sarafidis  3 , Dimitrios Magouliotis  4 , Thanos Athanasiou  5 , Ioannis Paraskevaidis  6 , John Skoularigis  7 , Andrew Xanthopoulos  7
Affiliations
Review

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF

Filippos Triposkiadis et al. J Clin Med. .

Abstract

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

Keywords: heart failure; hypertension; sympathetic overactivity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The central sympathetic nervous system [SNS] is located in the medulla and modulated by the hypothalamus. The motor outflow of the SNS is formed by two sets of neurons connected in tandem, the pre-ganglionic neurons originating in the brain stem or the spinal cord, and the post-ganglionic neurons located in the sympathetic ganglia. The main neurotransmitter of the SNS pre-ganglionic neurons is acetylcholine, while the main neurotransmitter of most SNS post-ganglionic neurons is norepinephrine. SNS activity is decreased (–) by the arterial baroreceptor reflex and the cardiopulmonary reflex and augmented (+) by the cardiac SNS afferent reflex (CSAR) and the arterial chemoreceptor reflex. H = hypothalamus; M = medulla. With permission from ref. [1].
Figure 2
Figure 2
Schematic representation of β-AR signaling in cardiomyocytes. CAs, catecholamines; β-AR, β-adrenergic receptor; G protein subunits: Gα (Gαs or Gαi), Gβ, Gγ; GRK2, G protein-coupled receptor kinase 2; AC, adenylyl cyclase; ATP, adenosine tri-phosphate; cAMP, cyclic adenosine mono-phosphate; PDE, phosphodiesterase; PKA, protein kinase A. A blue arrow is used when a stimulatory mechanism is involved while a red bar-headed line is used for an inhibitory mechanism. With permission from ref. [25].
Figure 3
Figure 3
Example of placing a circular or elliptical region of interest (ROI) over the heart (H) and fixed rectangular mediastinal ROI placed on the upper part of the mediastinum (M) for calculating heart-to-mediastinum ratio (H/M). The same ROIs are placed on early and late images to calculate H/M and washout. The H/M outcomes are standardized to the ME-collimator condition. With permission from ref. [79].
Figure 4
Figure 4
Implementation of medical treatment in hypertensive heart failure (HHF). The presence of elevated blood pressure (BP) in HHF as well as the renoprotective effects of finerenone, which rarely causes early hyperkalemia, allows ultra-fast up-titration of HF medications. Treatment should start with the simultaneous use of sacubitril/valsartan, sodium glucose cotransporter 2 inhibitors (SGLT-2i), and mineralocorticoid receptor antagonists (MRAs, preferably finerenone). In HHF patients with eccentric left ventricular hypertrophy (LVH), β-blockers (preferably vasodilatory) should be started from the beginning, whereas in HHF patients with concentric LVH, β-blockers should be considered in those with atrial fibrillation, coronary artery disease, or resistant hypertension. A target systolic BP of 110–130 mmHg should be achieved within 45 days, and thereafter, systolic BP should remain within the therapeutic target range most of the time. TTR, Time in Therapeutic Range. With permission from ref. [13].
Figure 5
Figure 5
Neurohormonal pathways connecting the renal system to the central nervous system, cardiac, and vascular systems and the effect of renal denervation on those pathways (red arrows). With permission from ref. [105].
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References

    1. Triposkiadis F., Karayannis G., Giamouzis G., Skoularigis J., Louridas G., Butler J. The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J. Am. Coll. Cardiol. 2009;54:1747–1762. doi: 10.1016/j.jacc.2009.05.015. - DOI - PubMed
    1. Hartupee J., Mann D.L. Neurohormonal activation in heart failure with reduced ejection fraction. Nat. Rev. Cardiol. 2017;14:30–38. doi: 10.1038/nrcardio.2016.163. - DOI - PMC - PubMed
    1. Anker S.D., Butler J., Filippatos G., Ferreira J.P., Bocchi E., Bohm M., Brunner-La Rocca H.P., Choi D.J., Chopra V., Chuquiure-Valenzuela E., et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N. Engl. J. Med. 2021;385:1451–1461. doi: 10.1056/NEJMoa2107038. - DOI - PubMed
    1. Pitt B., Pfeffer M.A., Assmann S.F., Boineau R., Anand I.S., Claggett B., Clausell N., Desai A.S., Diaz R., Fleg J.L., et al. Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 2014;370:1383–1392. doi: 10.1056/NEJMoa1313731. - DOI - PubMed
    1. Solomon S.D., McMurray J.J.V., Anand I.S., Ge J., Lam C.S.P., Maggioni A.P., Martinez F., Packer M., Pfeffer M.A., Pieske B., et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N. Engl. J. Med. 2019;381:1609–1620. doi: 10.1056/NEJMoa1908655. - DOI - PubMed

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