Multi-organ denervation: a novel approach to combat cardiometabolic disease

Abstract

Cardiometabolic disorders are associated with a substantial loss in quality of life and pose a large burden on healthcare systems worldwide. Overactivation of the sympathetic nervous system has been shown to be a key player in several aspects relating to cardiometabolic disturbances. While diet- and exercise-induced approaches to help reduce weight remains the main strategy to combat metabolic disorders, this is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication side effects and non-adherence in the long term. There is a clear clinical need for complementary therapies to curb the burden of cardiometabolic disease. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. Data from sham-controlled clinical trials demonstrate the feasibility, safety and efficacy of catheter-based renal denervation. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multi-organ neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum including blood pressure, glucose and lipid control.

Keywords: Hepatic denervation; Hypertension; Renal denervation; Sympathetic nerve activity.

Fig. 1

Sympathetic nervous system effects on cardiometabolic control

Fig. 2

Effect of the sympathetic nervous system on cardio-metabolic homeostasis. Mechanistic overview of the potential effect of multi-organ denervation on cardiometabolism

Fig. 3

Renal and hepatic glucose release in type 2 diabetics

Fig. 4

Sympathetic overdrive cycle