Next generation renal denervation: Chemical 'perivascular' renal denervation with alcohol using a novel drug infusion catheter

摘要

Background/Purpose: We update the pre-clinical and early clinical results using a novel endovascular approach, to perform chemical renal denervation, via peri-adventitial injection of micro-doses of dehydrated alcohol (ethanol-EtOH). Methods/Materials: A novel, three-needle delivery device (Peregrine?) was used to denervate the renal arteries of adult swine (n. =. 17) and in a first-in-man feasibility study (n. =. 18). In the pre-clinical testing EtOH was infused bilaterally with one infusion per renal artery into to the perivascular space, using EtOH doses of 0.3. ml/artery (n. =. 8), and 0.6. ml/artery (n. =. 9), and with saline sham control (0.4. ml/artery n. =. 3). Renal parenchymal norepinephrine (NE) concentration (performed blindly), and safety were the primary endpoints. Data from the first-in-man study (n. =. 18) to evaluate device performance, safety and peri-procedural pain are reported. Results: In the pre-clinical testing renal function was unchanged at 3-month follow-up. Angiography at 90. days (n. =. 34 arteries) demonstrated normal appearing renal arteries, unchanged from baseline, and without stenosis or other abnormalities. The reductions in mean renal parenchymal NE reductions at 3. months were 68% and 88% at doses of 0.3 and 0.6. ml, respectively (p. <. 0.001 vs. controls). In the first-in-man study, there was 100% device success, no complications, a mean treatment time of 4.3. ±. 3. minutes/artery, and minimal or no patient discomfort during treatment. Angiography at 6-months showed no evidence of renal artery stenosis, and evidence of a reduction of blood pressure from baseline. Conclusion: Perivascular RDN using micro-doses of alcohol is a promising alternative to energy-based systems to achieve dose-dependent, predictable, safe and essentially painless renal denervation. Further clinical evaluation is warranted. Summary: (For annotated table of contents) This paper describes the preclinical results, in a porcine model, and the early first-in-man results, using the Peregrine? chemical renal denervation catheter to perform renal sympathetic denervation using micro-doses of alcohol.