{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:24:17Z","timestamp":1790796257060,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Hans und Ria Messer Stiftung","award":["HMS 20243118"],"award-info":[{"award-number":["HMS 20243118"]}]},{"name":"Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Res Cardiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertension may remain uncontrolled despite lifestyle measures, guideline-directed multidrug therapy, and renal denervation (RDN). Sympathetic overactivity contributes to persistent blood pressure (BP) elevation and cardiometabolic dysfunction. Given its central role in metabolic regulation and dense sympathetic innervation, the liver represents an attractive target for interventional neuromodulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This first-in-human ultrasound common hepatic artery denervation (CHA-D) was performed in a patient with recurrent uncontrolled hypertension and cardiometabolic comorbidity despite prior RDN and limited medical treatment options. Follow-up included ambulatory and office BP monitoring at 1 and 6\u00a0months, proton density fat fraction magnetic resonance imaging, metabolic parameters, and patient-reported outcomes (SF-36, EQ-5D-5L). In addition, current clinical studies evaluating CHA-D and multi-organ denervation were reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The procedure was completed successfully without intraprocedural complications. No hepatobiliary, pancreatic, or renal safety signal emerged during follow-up. Mean 24-h BP decreased from 179\/88\u00a0mmHg at baseline to 151\/87\u00a0mmHg at 1\u00a0month and 139\/83\u00a0mmHg at 6\u00a0months, corresponding to systolic BP reductions of 28 and 40\u00a0mmHg, respectively, without intensification of antihypertensive therapy. Office BP decreased from 176\/116\u00a0mmHg at baseline to 125\/85\u00a0mmHg at 6\u00a0months. Hepatic fat fraction declined from 16.2% to 11.5%, HbA1c from 6.2% to 5.9%, insulin requirement was reduced, and body weight decreased by 8\u00a0kg. Patient-reported outcomes also improved during follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This first-in-human experience suggests CHA-D as a technically feasible and safe neuromodulatory approach with convergent signals of hemodynamic and cardiometabolic benefit, supporting further prospective evaluation of CHA-D in cardiovascular-kidney-metabolic syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00392-026-02949-9","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:01:08Z","timestamp":1780466468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ultrasound common hepatic artery denervation (CHA-D) as a novel neuromodulatory strategy for cardiovascular-kidney-metabolic syndrome: first-in-human experience"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6059-1671","authenticated-orcid":false,"given":"Mert","family":"Tokcan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciska Diana","family":"Wolter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Hohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saarraaken","family":"Kulenthiran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"2949_CR1","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa2206916","volume":"389","author":"The Global Cardiovascular Risk Consortium","year":"2023","unstructured":"The Global Cardiovascular Risk Consortium (2023) Global effect of modifiable risk factors on cardiovascular disease and mortality. N Engl J Med 389:1273\u20131285","journal-title":"N Engl J Med"},{"key":"2949_CR2","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","volume":"45","author":"JW McEvoy","year":"2024","unstructured":"McEvoy JW, McCarthy CP, Bruno RM et al (2024) 2024 ESC guidelines for the management of elevated blood pressure and hypertension: developed by the task force on the management of elevated blood pressure and hypertension of the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). Eur Heart J 45:3912\u20134018","journal-title":"Eur Heart J"},{"key":"2949_CR3","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","volume":"398","author":"B Zhou","year":"2021","unstructured":"Zhou B, Carrillo-Larco RM, Danaei G et al (2021) Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. The Lancet 398:957\u2013980","journal-title":"The Lancet"},{"key":"2949_CR4","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1093\/ajh\/hpab124","volume":"34","author":"G Grassi","year":"2021","unstructured":"Grassi G (2021) The sympathetic nervous system in hypertension: roadmap update of a long journey. Am J Hypertens 34:1247\u20131254","journal-title":"Am J Hypertens"},{"key":"2949_CR5","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s11906-023-01254-4","volume":"25","author":"G Grassi","year":"2023","unstructured":"Grassi G, Dell\u2019Oro R, Quarti-Trevano F, Vanoli J, Oparil S (2023) Sympathetic neural mechanisms in hypertension: recent insights. Curr Hypertens Rep 25:263\u2013270","journal-title":"Curr Hypertens Rep"},{"key":"2949_CR6","doi-asserted-by":"crossref","unstructured":"Canale MP, Manca di Villahermosa S, Martino G et al (2013) Obesity-related metabolic syndrome: mechanisms of sympathetic overactivity. Int J Endocrinol 2013:865965","DOI":"10.1155\/2013\/865965"},{"key":"2949_CR7","doi-asserted-by":"publisher","first-page":"2476","DOI":"10.1016\/S0140-6736(21)00788-1","volume":"397","author":"M Azizi","year":"2021","unstructured":"Azizi M, Sanghvi K, Saxena M et al (2021) Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. The Lancet 397:2476\u20132486","journal-title":"The Lancet"},{"key":"2949_CR8","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/S0140-6736(20)30554-7","volume":"395","author":"M B\u00f6hm","year":"2020","unstructured":"B\u00f6hm M, Kario K, Kandzari DE et al (2020) Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. The Lancet 395:1444\u20131451","journal-title":"The Lancet"},{"key":"2949_CR9","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1016\/S0140-6736(18)31082-1","volume":"391","author":"M Azizi","year":"2018","unstructured":"Azizi M, Schmieder RE, Mahfoud F et al (2018) Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. The Lancet 391:2335\u20132345","journal-title":"The Lancet"},{"key":"2949_CR10","doi-asserted-by":"crossref","unstructured":"B\u00f6hm M, Mahfoud F, Townsend RR et al (2018) Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. The Lancet 391:2346\u20132355","DOI":"10.1016\/S0140-6736(18)30951-6"},{"key":"2949_CR11","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1002\/ejhf.3147","volume":"26","author":"A Abdin","year":"2024","unstructured":"Abdin A, Lauder L, Fudim M et al (2024) Neuromodulation interventions in the management of heart failure. Eur J Heart Fail 26:502\u2013510","journal-title":"Eur J Heart Fail"},{"key":"2949_CR12","doi-asserted-by":"crossref","unstructured":"Tokcan M, Hohl M, Schneider CV et al (2026) Renal denervation improves hepatic steatosis in hypertensive patients with metabolic syndrome. Hypertension\u00a083(4):e26601","DOI":"10.1161\/HYPERTENSIONAHA.125.26601"},{"key":"2949_CR13","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1161\/CIRCULATIONAHA.110.991869","volume":"123","author":"F Mahfoud","year":"2011","unstructured":"Mahfoud F, Schlaich M, Kindermann I et al (2011) Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension. Circulation 123:1940\u20131946","journal-title":"Circulation"},{"key":"2949_CR14","doi-asserted-by":"crossref","unstructured":"Tzafriri AR, Garcia-Polite F, Keating J et al (2022) Morphometric analysis of the human common hepatic artery reveals a rich and accessible target for sympathetic liver denervation. Sci Rep\u00a012(1):1413","DOI":"10.1038\/s41598-022-05475-6"},{"key":"2949_CR15","doi-asserted-by":"publisher","first-page":"4565","DOI":"10.1113\/JP277994","volume":"597","author":"C Hurr","year":"2019","unstructured":"Hurr C, Simonyan H, Morgan DA, Rahmouni K, Young CN (2019) Liver sympathetic denervation reverses obesity-induced hepatic steatosis. J Physiol 597:4565\u20134580","journal-title":"J Physiol"},{"key":"2949_CR16","doi-asserted-by":"publisher","first-page":"17","DOI":"10.7150\/ijbs.2.17","volume":"2","author":"M Franco-Col\u00edn","year":"2006","unstructured":"Franco-Col\u00edn M, Villanueva I, Pi\u00f1\u00f3n M, Racotta R (2006) The effects of sympathectomy and dexamethasone in rats ingesting sucrose. Int J Biol Sci 2:17\u201322","journal-title":"Int J Biol Sci"},{"key":"2949_CR17","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1007\/s00392-021-01814-1","volume":"110","author":"MG Kiuchi","year":"2021","unstructured":"Kiuchi MG, Ganesan K, Keating J et al (2021) 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. Clin Res Cardiol 110:740\u2013753","journal-title":"Clin Res Cardiol"},{"key":"2949_CR18","doi-asserted-by":"publisher","first-page":"e1028","DOI":"10.4244\/EIJ-D-25-00349","volume":"21","author":"F Mahfoud","year":"2025","unstructured":"Mahfoud F, Tunev S, Kandzari DE et al (2025) A preclinical study of combined hepatic and renal artery denervation. EuroIntervention 21:e1028\u2013e1036","journal-title":"EuroIntervention"},{"key":"2949_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.09.291","volume":"86","author":"K Sievert","year":"2025","unstructured":"Sievert K, Gogorishvili I, Sievert H (2025) TCT-208 multi-organ arterial denervation for the treatment of type 2 diabetes mellitus and its comorbidities (NECTAR IV trial). JACC 86:B93","journal-title":"JACC"},{"key":"2949_CR20","doi-asserted-by":"crossref","unstructured":"Wang Z, Pan T, Lv W et al (2025) Catheter-based endovascular celiac and hepatic denervation for type 2 diabetes: a multicenter, open-label, single-arm study. Signal Transduct Target Ther\u00a010:371","DOI":"10.1038\/s41392-025-02459-6"},{"key":"2949_CR21","doi-asserted-by":"crossref","unstructured":"Mchorney CA, Johne WR, Anastasiae R. The MOS 36-item short-form health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care. 1993;31.","DOI":"10.1097\/00005650-199303000-00006"},{"key":"2949_CR22","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1007\/s11136-011-9903-x","volume":"20","author":"M Herdman","year":"2011","unstructured":"Herdman M, Gudex C, Lloyd A et al (2011) Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 20:1727\u20131736","journal-title":"Qual Life Res"},{"key":"2949_CR23","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41440-024-01596-9","volume":"47","author":"M Katsuki","year":"2024","unstructured":"Katsuki M, Shinohara K, Kinugawa S, Hirooka Y (2024) The effects of renal denervation on blood pressure, cardiac hypertrophy, and sympathetic activity during the established phase of hypertension in spontaneously hypertensive rats. Hypertens Res 47:1073\u20131077","journal-title":"Hypertens Res"},{"key":"2949_CR24","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1038\/s41440-024-01677-9","volume":"47","author":"K Katsurada","year":"2024","unstructured":"Katsurada K, Patel KP (2024) The role of afferent renal nerves in regulating sympathetic outflow via central nervous system mechanisms. Hypertens Res 47:1978\u20131980","journal-title":"Hypertens Res"},{"key":"2949_CR25","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/HYPERTENSIONAHA.111.00474","volume":"61","author":"JD Foss","year":"2013","unstructured":"Foss JD, Fink GD, Osborn JW (2013) Reversal of genetic salt-sensitive hypertension by targeted sympathetic ablation. Hypertension 61:806\u2013811","journal-title":"Hypertension"},{"key":"2949_CR26","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1161\/HYPERTENSIONAHA.108.119990","volume":"53","author":"GD Fink","year":"2009","unstructured":"Fink GD (2009) Sympathetic activity, vascular capacitance, and long-term regulation of arterial pressure. Hypertension 53:307\u2013312","journal-title":"Hypertension"},{"key":"2949_CR27","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1080\/1744666X.2025.2511265","volume":"21","author":"CFC Frazatto","year":"2025","unstructured":"Frazatto CFC, Martinez ARM, Appenzeller S (2025) Dysautonomia in systemic lupus erythematosus: When to suspect and how to investigate. Expert Rev Clin Immunol 21:701\u2013710","journal-title":"Expert Rev Clin Immunol"},{"key":"2949_CR28","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2021-000507","volume":"8","author":"AH Zinglersen","year":"2021","unstructured":"Zinglersen AH, Iversen KK, Leffers HCB, Laugesen E, Fleischer J, Jacobsen S (2021) Characteristics of cardiovascular autonomic dysfunction and association with quality of life in patients with systemic lupus erythematosus. Lupus Sci Med 8:e000507","journal-title":"Lupus Sci Med"},{"key":"2949_CR29","doi-asserted-by":"crossref","unstructured":"Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117\u20132128","DOI":"10.1056\/NEJMoa1504720"},{"key":"2949_CR30","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S2213-8587(14)70033-6","volume":"3","author":"M Schlaich","year":"2015","unstructured":"Schlaich M, Straznicky N, Lambert E, Lambert G (2015) Metabolic syndrome: A sympathetic disease? Lancet Diabetes Endocrinol 3:148\u2013157","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2949_CR31","doi-asserted-by":"crossref","unstructured":"Mancia G, Bousquet P, Elghozi JL et al (2007) The sympathetic nervous system and the metabolic syndrome. J Hypertens 25:909\u2013920","DOI":"10.1097\/HJH.0b013e328048d004"}],"container-title":["Clinical Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-026-02949-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00392-026-02949-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-026-02949-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:01:13Z","timestamp":1780466473000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00392-026-02949-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":31,"alternative-id":["2949"],"URL":"https:\/\/doi.org\/10.1007\/s00392-026-02949-9","relation":{},"ISSN":["1861-0684","1861-0692"],"issn-type":[{"value":"1861-0684","type":"print"},{"value":"1861-0692","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"13 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"After detailed discussion of the experimental nature of the procedure and its potential risks, the patient provided written informed consent for the intervention and for publication. According to local regulations, formal ethics committee approval was not required for this compassionate-use single-case intervention. All procedures performed were in accordance with local ethical standards and with the Declaration of Helsinki and its later amendments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statement"}},{"value":"MT received personal fees from Recor Medical and is supported by the Hans und Ria Messer Stiftung (HMS 20243118). TK received personal fees from Abbott, AstraZeneca, Bristol-Myers Squibb, Recor Medical, Shockwave Medical, and Translumina. TK is named inventor on patent applications for prevention of restenosis after angioplasty and stent implantation and for the prevention and treatment of atherosclerosis using antisense oligonucleotides, all of which are unrelated to the submitted work. MB is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Edwards, Medtronic, Novartis, ReCor, Servier, and Vifor. FDW, PF, SK, and MH have nothing to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}