Carotid body modulation in systolic heart failure from the clinical perspective

Abstract

Augmented sensitivity of peripheral chemoreceptors (PChS) is a common finding in systolic heart failure (HF). It is related to lower left ventricle systolic function, higher plasma concentrations of natriuretic peptides, worse exercise tolerance and greater prevalence of atrial fibrillation compared to patients with normal PChS. The magnitude of ventilatory response to the activation of peripheral chemoreceptors is proportional to the level of heart rate (tachycardia) and blood pressure (hypertension) responses. All these responses can be measured non-invasively in a safe and reproducible fashion using different methods employing either hypoxia or hypercapnia. Current interventions aimed at modulation of peripheral chemoreceptors in HF are focused on carotid bodies (CBs). There is a clear link between afferent signalling from CBs and sympathetic overactivity, which remains the priority target of modern HF treatment. However, CB modulation therapies may face several potential obstacles: (1) As evidenced by HF trials, an excessive inhibition of sympathetic system may be harmful. (2) Proximity of critical anatomical structures (important vessels and nerves) makes surgical and transcutaneous interventions on CB technically demanding. (3) Co-existence of atherosclerosis in the area of carotid artery bifurcation increases the risk of central embolic events related to CB modulation. (4) The relative contribution Piotr Niewinski is clinical scientist and active cardiologist specializing in heart failure and invasive electrophysiology. He received his PhD from Wroclaw Medical University in 2015 for his research focused on pathophysiology of peripheral chemoreceptors in systolic heart failure. He was involved in first-in-man trials of carotid body modulation. He is a member of the Polish Society of Cardiology and European Society of Cardiology.This review was presented at the meeting of International Society for Autonomic Neuroscience, which took place in Stresa, Italy on 27 September 2015. of CBs vs. aortic bodies to sympathetic activation in HF patients is unclear. (5) Choosing optimal candidates for CB modulation from the population of HF patients may be problematic. (6) There is a risk of nocturnal hypoxia following CB ablation -mostly after bilateral procedures and in patients with concomitant obstructive sleep apnoea. Abstract figure legend Potential risk and benefits of carotid body modulation in systolic heart failure.Abbreviations AB, aortic body; CB, carotid body; HF, heart failure; HR, heart rate; HVR, hypoxic ventilatory response; P aCO2 , partial pressure of carbon dioxide in arterial blood; P aO2 , partial pressure of oxygen in arterial blood; PChR, peripheral chemoreceptors; PChS, peripheral chemosensitivity; SBP, systolic blood pressure; S pO2 , peripheral capillary oxygen saturation.

Simultaneous assessment of central and peripheral chemoreflex regulation of muscle sympathetic nerve activity and ventilation in healthy young men

“…Importantly, selection thus far of patients for peripheral chemoreceptor interventions has been based on their ventilatory, rather than their sympatho‐neural, response to hypoxia (Niewinski et al . , ; Narkiewicz et al . ), without, in general, specific attention to the concurrent peripheral and central respiratory thresholds.…”

“…Indeed, chemoreceptor‐specific interventions such as carotid body ablation have been proposed for patients with exaggerated sympathetic activation due to heart failure (Niewinski et al . , ) or drug‐resistant, and presumably neurogenic, hypertension (Paton et al . ; Narkiewicz et al .…”

“…). These strategies are predicated on the as yet untested presumption that an augmented ventilatory response to peripheral chemoreflex stimulation, by hypoxia, will identify an individual with a similarly exaggerated sympathetic response (Niewinski, ).…”

Carotid chemoreflex activity restrains post‐exercise cardiac autonomic control in healthy humans and in patients with pulmonary arterial hypertension

“…). However, this approach may be useful only when other less aggressive strategies have failed (Niewinski, ). Thus, pharmacological strategies, such as selective inhibitors of P2X3 receptors (Pijacka et al .…”

Targeting autonomic imbalance in pathophysiology: is the carotid body the new nirvana?

“…The aforementioned papers were based on animal models that have led the authors to make clinical predictions about removing carotid bodies to alleviate disease symptoms; these have included insulin resistance, hypertension and sympathetic excess. The paper presented by Niewinski () considers possible surgical complications and outcomes if carotid bodies are removed from patients with systolic heart failure. A phenotype of heart failure includes an exaggerated respiratory response to transient breathing of nitrogen.…”