FOCUS ON SYMPATHETIC DENERVATION

Long-term stimulation of sympathetic activity has been linked to the pathophysiology of chronic diseases such as systemic hypertension, metabolic syndrome, sleep apnea, heart failure, liver cirrhosis and rheumatoid arthritis. Thus, reduction of sympathetic nerve activity via local nerve ablation has emerged as an attractive therapy for hypertension and other chronic diseases. As a result, the last decade has witnessed intense research into minimally invasive renal sympathetic denervation — from catheter-based drug delivery systems to sonic and RF ablation devices.

Since the inception of this novel technology, CBSET has led the way in developing animal models for assessing safety, as well as quantitative methods for assessing and understanding efficacy, including biomarker assays, histomorphometry, and even computational modeling. These have been presented in international conferences and published in peer-reviewed journals, cementing CBSET’s status as a key opinion leader in the evaluation of neuroablation technologies.


Renal Denervation

CBSET has developed specialized expertise in the development and application of minimally invasive device-based interventional therapies for renal denervation.
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CBSET-authored papers and presentations related to sympathetic denervation:

HIGHLIGHT OF THE MONTH

"Renal sympathetic nerve denervation using intraluminal ultrasound within a cooling balloon preserves the arterial wall and reduces sympathetic nerve activity."

Pathak A, Coleman L, Roth A, Stanley J, Bailey L, Markham P, Ewen S, Morel C, Despas F, Honton B, Senard JM, Fajadet J, Mahfoud F.

EuroIntervention. 2015 Aug 22;11(4):477-84.

"Morphometric analysis of the human common hepatic artery (CHA) reveals a rich and accessible target for sympathetic liver denervation." Abraham Rami Tzafriri PhD, Fernando Garcia-Polite PhD, John Keating DVM DACVP, Raffaele Melidone DVM DACVP, Jennifer Knutson BS, Peter Markham MS, Elazer R. Edelman MD PhD, Felix Mahfoud MD. Scientific Reports, 10.1038/s41598-022-05475-6

"Clinical Research in Cardiology: 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." Márcio Galindo Kiuchi, Kavitha Ganesan, John Keating, Revathy Carnagarin, Vance B Matthews, Lakshini Y Herat, Gerard Goh, Leon Adams, Markus P Schlaich. Clin Res Cardiol. 2021 May;110(5):740-753. doi: 10.1007/s00392-021-01814-1.

"Pulsed Field Ablation Using a Lattice Electrode for Focal Energy Delivery: Biophysical Characterization, Lesion Durability, and Safety Evaluation." Hagai Yavin, Ayelet Shapira-Daniels, Michael Barkagan, Jakub Sroubek, David Shim, Raffaele Melidone, Elad Anter. Circulation: Arrhythmia and Electrophysiology 2020 Jun;13(6):e008580. 

"Procedural and Anatomical Determinants of Multi-Electrode Renal Denervation: Preclinical Versus Clinical." Abraham Tzafriri, PhD. Invited presentation at: CRT 2020, Feb 22-25; National Harbor, MD. 

denervation-microanatomy300px"Splenic artery denervation: target micro-anatomy, feasibility, and early preclinical experience." Mazen Albaghdadi, Fernando Garcia-Polite, Brett Zani, John Keating, Raffaele Melidone, Anna Spognardi, Peter Markham, Abraham Tzafriri. Translational Research. doi:10.1016/j.trsl.2019.07.012. 

546ga1"Procedural and Anatomical Determinants of Multielectrode Renal Denervation Efficacy." Tzafriri AR, Mahfoud F, Keating JH, Spognardi AM, Markham PM, Wong G, Highsmith D, O'Fallon P, Fuimaono K, Edelman ER. hypertensionhighimpactpapers

Hypertension. 2019 Sep;74(3):546-554. doi: 10.1161/HYPERTENSIONAHA.119.12918.

"Pulmonary Artery Denervation Using Catheter based Ultrasonic Energy."Rothman A, Jonas M, Castel D, Tzafriri AR, Traxler H, Shav D, Leon MB, Ben-Yehuda O, Rubin L. EuroIntervention. 2019 May 7. pii: EIJ-D-18-01082. doi: 10.4244/EIJ-D-18-01082. 

scitransmed-cover"Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension." Tzafriri AR, Keating JH, Markham PM, Spognardi AM, L Stanley JR, Wong G, Zani BG, Highsmith D, O’Fallon P, Fuimaono K, Mahfoud F, Edelman ER. Science Translational Medicine. 2015 Apr 29;7(285):285ra65. doi: 10.1126/scitranslmed.aaa3236.

"Renal denervation: Not as easy as it looks." Editorial in Science Translational Medicine by Murray Esler Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.

"Microanatomy impacts on RDN." Editorial in Nature Reviews Nephrology by Jessica K. Edwards.

"Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation." Sakakura K, Ladich E, Fuimaono K, Grunewald D, O’Fallon P, Spognardi AM, Markham P, Otsuka F, Yahagi K, Shen K, Kolodgie FD, Joner M, Virmani R. Circulation: Cardiovascular Interventions. 2014 Dec 31;8(1). pii: e001720. doi: 10.1161.

"Innervation patterns may limit response to endovascular renal denervation." Tzafriri AR, Mahfoud F, Keating JH, Markham PM, Spognardi A, Wong G, Fuimaono K, Böhm M, Edelman ER. Journal of the American College of Cardiology. 2014 Sep 16;64(11):1079-87.

"Renal Denervation for Resistant Hypertension: Not Dead Yet." Editorial highlight of JACC article by Vivek Y. Reddy MD and Jeffrey W. Olin DO.

renaldenervationchart"Methodological Standardization for the Pre-Clinical Evaluation of Renal Sympathetic Denervation." Sakakura K, Ladich E, Edelman ER, Markham P, Stanley JR, Keating J, Kolodgie FD, Virmani R, Joner M. JACC Cardiovasc Interv. 2014 Sep 9.

"Evaluation of renal nerve morphological changes and norepinephrine levels following treatment with novel bipolar radiofrequency delivery systems in a porcine model." Cohen-Mazor M, Mathur P, Stanley JR, Mendelsohn FO, Lee H, Baird R, Zani BG, Markham PM, Rocha-Singh K. J Hypertens. 2014 May 28


CBSET-authored clinical papers related to sympathetic denervation:

"Anatomical and procedural determinants of ambulatory blood pressure lowering following catheter-based renal denervation using radiofrequency." Lauder L, Ewen S, Tzafriri AR, Edelman ER, Cremers B, Kulenthiran S, Ukena C, Linz D, Kindermann I, Tsioufis C, Scheller B, Böhm M, Mahfoud F. Cardiovasc Revasc Med. 2018 Oct - Nov;19(7 Pt B):845-851. doi: 10.1016/j.carrev.2018.02.016. 

"Renal artery anatomy assessed by quantitative analysis of selective renal artery in 1000 patients with hypertension." Lauder L, Ewen S, Tzafriri AR, Edelman ER, Lüscher TF, Blankenstijn PJ, Dörr O, Schlaich M, Sharif F, Voskuil M, Zeller T, Ukena C, Scheller B, Böhm M, Mahfoud F, EuroIntervention. 2018 May 20;14(1):121-128. doi: 10.4244/EIJ-D-18-00112. 

"Anatomical and procedural determinants of catheter-based renal denervation." S Ewen; C Ukena; T Luscher; M Bergmann; P Blankestijn; B Cremers; E Blessing; O Doerr; H Nef; M Schlaich; F Sharif; MVoskuil; T Zeller; AR Tzafriri; E Edelman; M Boehm; F Mahfoud. Cardiovasc Revasc Med. 2016 Oct - Nov;17(7):474-479. doi: 10.1016/j.carrev.2016.08.004.