An Open-label, Single-arm, Multicenter Feasibility Study Evaluating the Safety of Catheter-based Renal Denervation with DENEX™ in Patients with Uncontrolled Hypertension on Standard Medical Therapy

Abstract

Introduction: DENEX™ is a novel renal sympathetic denervation (RDN) system that is equipped with 3 electrodes that deliver radiofrequency energy to the renal nerves along renal arteries. The purpose of this study was to evaluate the safety and efficacy of RDN with DENEX™ in resistant hypertension. Methods: This was an open-label, single-arm, multicenter, first-in-man pilot study. Between March 2012 and August 2019, a total of 16 patients were enrolled at 4 centers in South Korea. The inclusion criteria were systolic blood pressure (SBP) ≥150 mmHg and use of 3 or more antihypertensive medications, including diuretics. The primary objective was the safety outcome of RDN with the DENEX™ system. The secondary objective was efficacy outcome based on changes of office, and 24-hour ambulatory SBP from baseline to 3 months. The patients underwent abdominal computed tomography (CT) or duplex ultrasonogram before and 6 months after RDN. Results: No major adverse events occurred after RDN for 6 month of follow-up period. There was no vascular complication either by CT or duplex ultrasonogram. The office SBP was significantly reduced from 164.6±11.6 mmHg at baseline to 142.0±20.4 mmHg (−24.4±24.4 mmHg, p=0.003) at 3 months. The ambulatory SBP was reduced from 151.44±12.85 mmHg at baseline to 140.0±16.5 mmHg (−13.1±18.9 mmHg, p=0.056) at 3 months. Conclusion: RDN with the DENEX™ system showed a favorable safety profile in resistant hypertension. A significant reduction in office SBP and a borderline reduction in ambulatory SBP were observed.

Clinical Effect of Renal Arterial Sympathetic Radiofrequency Ablation on Secondary Hypertension

“…Studies have shown that the sympathetic nervous system is a special regulatory system between the kidney and the brain and plays an important role in the blood pressure regulation of hypertensive patients. Local norepinephrine isotope dilution was used to measure renal norepinephrine outflow in patients with untreated hypertension [16][17][18][19][20]. Monitoring revealed a high level of renal sympathetic outflow activation, indicating renal sympathetic hyperactivity, which is the core mechanism of hypertension.…”

Effects of catheter‐based renal denervation on renin‐aldosterone system, catecholamines, and electrolytes: A systematic review and meta‐analysis

“…Follow‐up duration ranged from 0.5 to 72 months. Ten studies reported data on plasma renin, 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 nine studies on plasma aldosterone, 14 , 15 , 16 , 18 , 19 , 21 , 22 , 23 , 24 two studies on plasma norepinephrine, 20 , 25 seven studies on serum sodium, 23 , 24 , 26 , 27 , 28 , 29 , 30 nine studies on serum potassium, 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 five studies on urinary sodium, 18 , 20 , 24 , 26 , 33 and two studies on urinary potassium. 24 , 26 The characteristics of included studies are summarized in Table 1 .…”

Percutaneous renal denervation in the management of hypertension: Chinese expert scientific statement

“…During this phase, a variety of new ablation catheters with different designs and energy sources were developed and subsequently evaluated in clinical studies with sham-controlled. At present, in addition to Medtronic SYMPLICITY Flex™ and Spyral™ catheters, other RDN catheters certified by European Union (excluding discontinued devices) include those using radiofrequency energy: Iberis (Terumo Corporation, Tokyo, Japan) [19] , DENEX™ (Handok Kalos Medical, Seoul, Korea) [20] , ConfidenHT™ System (Pythagoras Medical Ltd, Herzliya, Israel) [21] ; those utilizing ultrasound energy: Paradise (Paradise ultrasound system; ReCor Medical, Palo Alto, CA, USA) [18] and TIVUS™ (CardioSonic, Tel Aviv, Israel) [22] ; and those using anhydrous alcohol injection for ablation: Peregrine (Ablative Solutions Inc., Wakefield, MA, United States) [23] . These catheters represent a diverse range of technologies aimed at achieving RDN, providing clinicians with various options to tailor treatment according to individual patient needs and preferences.…”