Twelve Week Safety and Efficacy of a Novel Extravascular Bi-lateral Renal Denervation Device in a Porcine Model at Nominal Dose.
Chang Wook Jeong, Jay Budrewicz, John H. Keating, Misty Williams-Fritze, Peter Markham, Rami Tzafriri.
Background: Catheter-based renal denervation (RDN) is limited to accessible renal arteries (≥3mm). Performance of an extravascular radiofrequency (RF) device that circumferentially wraps the renal artery was tested in pigs.
Methods: Per preliminary optimization, 38 swine renal arteries (outer diameters=2-9mm) underwent nominal dose (50oC/70sec) bilateral laparoscopic RDN procedures, on Day 0 using the HyperQure™ RDN System (DeepQure Inc., Seoul, Republic of Korea). Abdominal CT scans were performed pre/post procedure. Acute performance was evaluated by 3 surgeons. Animal health was regularly monitored. Animals were euthanized at Days 7, 28 and 84, and subjected to a comprehensive necropsy. Tissues were collected for histology (H&E and tyrosine hydroxylase (TH)) and a portion of each kidney was processed and analyzed for Norepi D6 (NEPI) content.
Results: All treatments achieved the highest average acute performance scores with no observed post-treatment arterial injuries or spasms. There were 4 early deaths, which could not be directly attributed to the test device. Remaining animals exhibited good health with no complications resulting from test device treatment. CT scans showed minimal to absent stenosis. Acceptable arterial and periarterial/adventitial tissue responses were observed grossly and histologically, including nerve response to treatment, absence of adverse events, and complete healing and extensive remodeling of arterial and periarterial tissues by Day 84. Renal artery mural injury, luminal occlusion and thrombosis were absent and medial necrosis/smooth muscle cell loss was negligible across treatment groups. Adventitial/perivascular responses were consistent with initial changes induced by RF treatment resolving over time. Renal nerve responses decreased over time, being notable in TH-stained sections at Days 7 and 28, with prominent subsequent decrease in incidence at Day 84, attributed to repair/regeneration. Despite regeneration, mean NEPI concentration declined by ≥45% at all time points, relative to historical baseline.
Conclusions: Extravascular RDN of large and small arteries via laparoscopic access was safe and efficacious in pigs.
Presentation at TCT, October 27-30, 2024, Washington, DC.