Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model

Abstract

Background Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease. Objectives We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up. Methods Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety. Results All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (− 88%, p = 0.005), kidneys (− 78%, p < 0.001), pancreas (− 78%, p = 0.018) and duodenum (− 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up. Conclusions Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.

Decreasing the blood flow of non-compressible intra-abdominal organs with non-invasive transcutaneous electrical stimulation

“…In this context, continuous monitorisation of MAP is essential to reveal the immediate, acute, and long-term effects of non-invasive abdominal electrical stimulation. Combined denervation of the hepatic and renal arteries has also been investigated in the literature and demonstrated to be capable of reducing cardiometabolic risk [22]. The present study also demonstrated the effect of abdominal con guration on both the hepatic and renal artery modulation which may have an impact on cardiometabolic risk.…”

Device-Based Sympathetic Nerve Regulation for Cardiovascular Diseases

“…In addition, the Metavention has developed an integrated catheter ablation system, the iRF Denervation System (Metavention, Maple Grove, MN, USA), which allows for combined denervation of the hepatic and renal arteries. A significant decrease in norepinephrine concentrations in liver and kidney tissues at 90 days after the procedure compared with baseline (all p < 0.05), suggesting the possible effectiveness of combined ablation ( 142 ). Clinical studies on the iRF system were also conducted in 2020, and the DeLIVER study (NCT04285554) aimed to explore the safety of the iRF system and its effects on metabolic markers such as blood glucose and lipids, and its results are expected.…”

Interventional metabology: A review of bariatric arterial embolization and endovascular denervation for treating metabolic disorders

“…Kraft et al 59 established that surgical sympathetic denervation of the common hepatic artery in a canine model decreased both the hepatic and β‐cell defects caused by a high‐fat, high‐fructose diet, thereby increasing glucose tolerance. Kiuchi et al 61 investigated the feasibility, safety, and efficacy of EDN of both hepatic and renal arteries in a swine model, achieving significant and sustained denervation without major safety events. Tzafriri et al 62 analyzed the nerves and adjacent anatomies surrounding the human common hepatic artery to guide the clinical translation of catheter‐based denervation.…”