Ultrasound common hepatic artery denervation (CHA-D) as a novel neuromodulatory strategy for cardiovascular-kidney-metabolic syndrome: first-in-human experience

Clinical Research in Cardiology https://doi.org/10.1007/s00392-026-02949-9 ORIGINAL PAPER Ultrasound common hepatic artery denervation (CHA‑D) as a novel neuromodulatory strategy for cardiovascular‑kidney‑metabolic syndrome: first‑in‑human experience Mert Tokcan1,2 · Franciska Diana Wolter1 · Mathias Hohl1 · Peter Fries3 · Thorsten Kessler1,2 · Saarraaken Kulenthiran1,2 · Michael Böhm1,2 Received: 13 April 2026 / Accepted: 19 May 2026 © The Author(s) 2026 Abstract Background 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. Methods 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 months, 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. Results 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 mmHg at baseline to 151/87 mmHg at 1 month and 139/83 mmHg at 6 months, corresponding to systolic BP reductions of 28 and 40 mmHg, respectively, without intensification of antihypertensive therapy. Office BP decreased from 176/116 mmHg at baseline to 125/85 mmHg at 6 months. 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 kg. Patient-reported outcomes also improved during follow-up. Conclusion 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. Saarraaken Kulenthiran and Michael Böhm share last authorship. * Mert Tokcan 1 Klinik für Innere Medizin III – Kardiologie, Angiologie und Internistische Intensivmedizin, Saarland University Medical Center, Saarland University, Homburg, Germany 2 HOMICAREM (HOMburg Institute of CArdioREnalMetabolic Medicine), Medical Faculty, Saarland University, Homburg, Germany 3 Klinik Für Diagnostische Und Interventionelle Radiologie, Saarland University Medical Center, Saarland University, Homburg, Germany Vol.:(0123456789) Clinical Research in Cardiology Graphical Abstract Keywords Common hepatic artery denervation · Hypertension · Cardiovascular-kidney-metabolic syndrome · Sympathetic nervous system · Cardiometabolic Abbreviations BP Blood pressure CHA Common hepatic artery CHA-D Common hepatic artery denervation HbA1c Glycated hemoglobin A1c PDFF-MRI Proton density fat fraction magnetic resonance imaging RDN Renal denervation Introduction Hypertension is the most prevalent and potent contributor to cardiovascular morbidity and mortality [1]. However, a considerable proportion of patients fail to achieve guidelinerecommended blood pressure (BP) targets despite lifestyle modification and multidrug antihypertensive therapy [2, 3]. Uncontrolled hypertension is characterized by heightened sympathetic nervous system activity [4], which contributes to persistent BP elevation and metabolic dysregulation promoting target-organ damage [5, 6]. Catheter-based renal denervation (RDN) is a guideline-approved devicebased option for selected patients with uncontrolled or resistant hypertension, supported by sham-controlled trials demonstrating consistent BP reductions [2, 7–11]. Beyond BP reduction, translational evidence suggests that RDN may also exert favorable effects on cardiometabolic parameters including fasting glucose and hepatic steatosis [12, 13]. The liver represents an attractive target as it is the central organ of glucose and lipid homeostasis and is richly innervated by sympathetic fibers [14]. In experimental models, interruption of hepatic sympathetic signaling has been associated with reduced hepatic steatosis and improved glucose tolerance [15, 16]. Preclinical studies of combined RDN and common hepatic artery denervation (CHA-D) further support this concept [17, 18], and early clinical observations suggest that CHA-D may provide additional BP lowering and enhance the effects of RDN [19, 20]. This study presents the first-in-human use of ultrasound CHA-D in a non-responder to RDN with uncontrolled hypertension and a high cardiometabolic risk profile. The procedure, periprocedural safety, and longitudinal follow-up Clinical Research in Cardiology are described, including BP, laboratory parameters, and proton density fat fraction magnetic resonance imaging (PDFF-MRI). The case is further placed in the context of ongoing clinical studies evaluating CHA-D and multi-organ denervation strategies. Methods Liver CHA-D CHA CT Patient selection Ultrasound CHA-D was performed as an individual therapeutic attempt in a patient with symptomatic uncontrolled ar ter ial hyper tension and limited pharmacological treatment options owing to multiple intolerances and allergies to antihypertensive medications. Early target-organ damage and pronounced cardiometabolic comorbidity further underscored the severity of the clinical condition. The procedure was undertaken after established treatment strategies, including lifestyle measures, pharmacotherapy, and previous RDN, had failed to provide permanent BP control. The indication for CHA-D was determined by an interdisciplinary team with expertise in hypertension management and endovascular interventions. Potentially reversible contributors and secondary causes of hypertension were assessed and excluded as clinically appropriate. 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 compassionateuse single-case intervention. All procedures performed were in accordance with local ethical standards and with the Declaration of Helsinki and its later amendments. Pre‑procedural workup Anatomical eligibility was assessed by contrastenhanced computed tomography angiography to identify celiac–hepatic variants and to exclude relevant stenoses, dissections, aneurysms, or other findings that could compromise safe catheter navigation and treatment planning (Fig. 1). Because p (...truncated)