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. 2025 Sep 1;21(17):e1028-e1036.
doi: 10.4244/EIJ-D-25-00349.

A preclinical study of combined hepatic and renal artery denervation

Felix Mahfoud  1 , Stefan Tunev  2 , David E Kandzari  3 , Eric A Secemsky  4 , Pam R Taub  5 , Raven A Voora  6 , Lucas Lauder  1 , Cian Ryan  2 , Julie Trudel  2 , Douglas A Hettrick  2 , Markus Schlaich  7
Affiliations

A preclinical study of combined hepatic and renal artery denervation

Felix Mahfoud et al. EuroIntervention. .

Abstract

Background: Overactivity of the hepatic and renal sympathetic nerves is associated with chronic cardiovascular and metabolic conditions, including hypertension.

Aims: We studied the effect of combined renal and hepatic denervation through treatment of the common hepatic artery and the renal arteries.

Methods: Denervation was performed in the common hepatic artery and both renal arteries and their major branch vessels in normotensive swine using the same multielectrode radiofrequency (RF) ablation catheter (Symplicity Spyral). Renal and liver tissue samples were obtained for histological examination in two cohorts at 7 and 28 days post-procedure (n=5 sham, n=10 denervation for each timepoint).

Results: Combined hepatic and renal denervation was successfully achieved in all animals. At 7 days, the mean lesion depth was 5.8±1.4 mm in the renal arteries and 4.7±0.7 mm in the hepatic artery. Compared with controls, the mean renal cortical norepinephrine (NE) levels were reduced by 88.2% in the 7-day model and by 84.5% in the 28-day model. Liver NE decreased by 94.6% at 7 days and by 91.1% at 28 days (p<0.0001 for all comparisons with baseline). No inadvertent injury was detected in the treated arteries or adjacent tissues.

Conclusions: Combined hepatic and renal denervation using the same multielectrode RF denervation system resulted in a substantial reduction in both renal and hepatic tissue NE levels that was sustained up to 28 days without collateral tissue injury. These mechanistic findings may have implications for the treatment of chronic diseases impacted by hepatic and renal sympathetic nervous system overactivity.

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Conflict of interest statement

F. Mahfoud has been supported by Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. Saarland University has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical. Until May 2024, F. Mahfoud received speaker honoraria/consulting fees from Ablative Solutions, AstraZeneca, Inari Medical, Medtronic, Merck, Novartis, Philips, and ReCor Medical. D.E. Kandzari has received institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, Inc., OrbusNeich, Teleflex, Medtronic, and Ablative Solutions; and personal consulting honoraria from Cardiovascular Systems, Inc., Medtronic, and Abbott. E.A. Secemsky reports research funding from NIH from HLBI K23HL150290, U.S. Food & Drug Administration; institutional grants from Abbott, BD, Boston Scientific, Cook, Medtronic, and Philips; and consulting fees from Abbott, BD, Boston Scientific, Cook, Cordis, Endovascular Engineering, Gore, InfraRedx, Medtronic, Philips, RapidAI, Rampart, Shockwave Medical, Siemens, Teleflex, Terumo, Thrombolex, VentureMed, and Zoll. P.R. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the NIH (R01 DK118278-01 and R01 HL136407), the American Heart Association (SDG #15SDG2233005), and the Department of Homeland Security/FEMA (EMW-2016-FP-00788). R.A. Voora is a paid consultant and speaker for Medtronic and Mineralys Therapeutics. L. Lauder has received speaker honoraria from AstraZeneca, Medtronic, Pfizer, and ReCor Medical. S. Tunev, D.A. Hettrick, C. Ryan, and D. Trudel are full-time employees of Medtronic. M. Schlaich has received institutional grants or contracts and personal consulting fees from Medtronic, Abbott, and ReCor Medical; personal payment or honoraria from Medtronic, Abbott, Merck, and Servier Laboratories; personal support for attending meetings, travel, or both from Medtronic and Abbott; serves as the President of the High Blood Pressure Research Council of Australia; and is on the International Society of Hypertension scientific committee.

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