Sub-acute Safety and Efficacy Evaluation of Single versus Double Treatment Cycles of a Monopolar Radiofrequency Catheter-Based Renal Nerve Ablation and its Chronic Evolution in a Large Animal Model

Abstract

<p><strong>Aims:</strong>We aimed to evaluate the transcatheter renal denervation(RDN) effects delivered by a mono-electrode catheter in a large animal model including safety implications of delivery of one cycle versus two cycles of ablations.</p><p><strong>Methods and Results:</strong>18 animals underwent bilateral RDN; 4 untreated naïve swine were enrolled as controls for norepinephrine levels(NE) only. Animals recieved 120-second (follow up-7,30 and 90 days) or 240-second cycles ablations (follow up-7 days). Norepinephrine evaluation, histology and immunohistochemistry evaluation was performed. No luminal obstruction was observed at follow up. A 70% decrease in NE levels (76.68±57.87ng/g) was observed at 7 days, 81% at 30 days(49.05±45.81ng/g), and 51% at 90 days(12.7±73.2 ng/g) compared to naïve controls(254.1±54.1ng/g;p<0.05). Histologically, the thermal effect extended to a complete circumferential involvement with a depth ~8mm. The primary histological feature at 7 days was nerve necrosis and distal atrophy; at 30 days, necrosis was replaced by healing changes of fibrosis. Neuromatous regeneration was apparent at 30 days at RF treated levels. At 90 days these features progressed to become more conspicuous. There were no appreciable differences in depth and circumferential extent of RF injury between one and two cycle treatment groups.<strong></strong></p><p><strong>Conclusion:</strong>RDN performed with a mono-electrode catheter (Iberis) appears to be safe following single or double-cycle RF ablation.NE decrease following RDN was demonstrated at 7, 30, and 90 days compared to naïve controls, suggesting efficient nerve ablation with the device as intended for human use.</p>

Acute changes in histopathology and intravascular imaging after catheter‐based renal denervation in a porcine model

“…Angiographic luminal irregularity after RDN, which is known as “notch” in both clinical and animal studies , is suggested to be a sign of thickened media due to edema . However, in the current study, edematous swollen media was neither confirmed with light microscopy nor TEM (increased area of low electron density).…”

Safety of catheter‐based radiofrequency renal denervation on branch renal arteries in a porcine model

“…However, the reduction of renal norepinephrine concentration was less at 90 days than at 7 and 30 days. This result is in line with previous studies using healthy swine . Although the recovery mechanism has not yet been elucidated, previous animal studies suggest contribution of nerve regeneration .…”

“…This result is in line with previous studies using healthy swine. 24,36 Although the recovery mechanism has not yet been elucidated, previous animal studies suggest contribution of nerve regeneration. 26,37 Considering the long-lasting effects of RDN in humans, 38 recovery of renal norepinephrine concentration as early as 3 months after RDN seems to be specific to healthy animals.…”

“…The safety of RF‐RDN on the main RA has been confirmed in >1,000 patients, and histopathological changes induced by RF‐RDN around the main RA were assessed in several animal studies, However, the safety of RF‐RDN on the branch RA remains unclear. As the diameter of the branch RA is smaller than that of the main RA, there is a potential risk of disruption or stenosis.…”

Renal Sympathetic Denervation in Patients with Resistant Hypertension: A Feasibility Study

“…A catheter provided radial access to minimize vascular complications as well as femoral access. The safety and efficacy of the system were validated by the preclinical animal studies [11][12][13]. This system obtained CE approval in March 2013.…”