From the Research and Innovation Department, CBSET, Inc, Lexington, MA (A.R.T.), CBSET, Inc, Lexington.
Department of Internal Medicine III, Saarland University, Homburg/Saar, Germany (F.M.).
Hypertension. 2019 Sep;74(3):546-554. doi: 10.1161/HYPERTENSIONAHA.119.12918. Epub 2019 Jul 15.
Radiofrequency renal denervation is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on renal denervation treatment parameters and anatomic variables. One hundred twenty-nine porcine renal arteries were denervated with an irrigated radiofrequency catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7 days were characterized histomorphometrically and correlated with associated renal norepinephrine levels. Norepinephrine exhibited a threshold dependence on the percentage of affected nerves across the range of treatment durations (30-60 s) and power set points (6-20 W). For 15 W/30 s treatments, norepinephrine reduction and percentage of affected nerves tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥4 electrodes were powered. Histomorphometry and computational modeling both illustrated that radiofrequency treatments directed at large neighboring veins resulted in subaverage ablation areas and, therefore, contributed suboptimally to efficacy. Account for measured nerve distribution patterns and the annular geometry of the artery revealed that, regardless of treatment variables, total ablation area and circumferential coverage were the prime determinants of renal denervation efficacy, with increased efficacy at smaller diameters.
射频肾去神经术正在被研究用于治疗高血压,但其疗效存在差异。我们开发了临床前模型,以研究消融生物标志物对肾去神经治疗参数和解剖学变量的依赖性。使用带有多个螺旋排列电极的灌流射频导管对 129 个猪的肾动脉进行去神经处理。在第 7 天通过组织形态计量学对神经效应和消融几何形状进行了描述,并与相关的肾去甲肾上腺素水平相关联。去甲肾上腺素的水平与治疗时间(30-60 秒)和功率设定点(6-20 W)范围内受影响的神经百分比呈阈值依赖性。对于 15 W/30 s 的治疗,去甲肾上腺素的减少和受影响神经的百分比与电极治疗的次数相吻合,证实了螺旋交错消融的累加效应。只有在使用≥4 个电极供电时才能达到阈值效应。组织形态计量学和计算模型都表明,针对大的相邻静脉的射频治疗会导致平均消融面积减小,因此对疗效的贡献不理想。考虑到测量的神经分布模式和动脉的环形几何形状,无论治疗变量如何,总消融面积和圆周覆盖率都是肾去神经疗效的主要决定因素,在较小直径下疗效增加。