Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers

Abstract

Heart failure (HF) is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues. The sympathetic nervous system (SNS) is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes, circulating and neuronal catecholamine spillover, attenuated parasympathetic response, and augmented sympathetic outflow to the heart, kidneys and skeletal muscles. When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis, maladaptive ventricular and vascular remodeling, arrhythmogenesis, and poor prognosis in patients with HF. These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities. Therefore, this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF. Finally, special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF.

Keywords: Autonomic nervous system; Biomarkers; Catecholamines; Catestatin; Chromaffin system; Epinephrine; Heart failure; Myocardial failure; Norepinephrine; Sympathetic nervous system

Core tip: Sympathetic nervous system activation is one of the key neurohumoral mechanisms that are operative in heart failure and is robustly associated with adverse myocardial remodeling, arrhythmias, sudden cardiac death, and overall poor prognosis in this population. Therefore, adequate diagnosis and quantification of the degree of upregulated sympathetic nervous system activity must be assessed by the clinician in every heart failure patient. A special emphasis must be put on adequate treatment by neurohumoral antagonists such as beta-blockers that will mitigate these adverse effects and improve outcomes. The adjunct use of advanced imaging methods and novel biomarkers might aid in clinical decision-making.