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.

Clinical Implications of Uric Acid in Heart Failure: A Comprehensive Review

“…In multiple pathophysiological pathways that are operative in HF, such as myocardial necrosis, upregulation of the renin-angiotensin-aldosterone system (RAAS), overt activation of the sympathetic nervous system, and endothelial dysfunction, a recently recognized pathologic process of endothelial-to-mesenchymal transition (EndoMT) emerged as a potent pathobiological driver of pro-fibrotic signaling pathways in HF, thus leading to myocardial fibrosis and adverse ventricular remodeling [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. EndoMT is a dynamic shift in endothelial cell phenotype toward mesenchymal cells such as myofibroblasts, smooth muscle cells, and osteoblasts [ 24 ].…”

Why Do We Not Assess Sympathetic Nervous System Activity in Heart Failure Management: Might GRK2 Serve as a New Biomarker?

“…In physiological conditions, ANS exerts a fine regulation of cardiac and vascular functions through the integration of complex reflex responses, tuned by a balance between the parasympathetic and sympathetic functions. Those reflexes include the arterial baroreceptor reflex, peripheral and central chemoreceptor reflexes, cardiopulmonary mechanosensitive reflex, and pulmonary stretch receptor reflex [ 26 ]. In the past decades, Ewing and colleagues developed a battery of five noninvasive bedside tests to assess the ANS function in diabetic patients [ 27 ].…”

“…Alongside the biomarkers reflecting the pathophysiological processes of myocardial stress, systemic inflammation, and cardiac fibrosis, other molecules are specifically implicated in ANS activation and may potentially be employed in the management of HF patients [ 26 ]. A wide array of molecules is implicated in the pathophysiology of HF-related ANS derangement, and in the last decades, a relevant piece of scientific literature focused on them.…”

Innovative Approaches in Medicine

“…Most commonly HF is the consequence of the myocyte injury caused by coronary heart disease (CHD), uncontrolled arterial hypertension and diabetes mellitus, however, adverse myocardial remodeling can be triggered and sustained by valvular dysfunction, tachyarrhythmias (especially atrial fibrillation/flutter), interatrial and interventricular conduction abnormalities or pulmonary disorders such as chronic obstructive pulmonary disease or pulmonary arterial hypertension. Less common etiologies include cardiomyopathies, myocarditis, infections, systemic toxins, and cardiotoxic drugs that are nowadays increasingly used in various chemotherapeutic regimens [13].…”

“…Thus, early recognition and treatment, as well as the elimination of potentially reversible factors which play a role in the worsening of HF are crucial to improve both survival and health-related life quality in those with HF [12]. Equally important is the introduction in modern clinical practice of biomarkers that can help in the diagnosis, prognosis and risk stratification of patients with HF [13].…”