Procedural and Anatomical Determinants of Multielectrode Renal Denervation Efficacy

Radiofrequency renal denervation (RDN) is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on RDN treatment parameters and anatomical variables. 129 porcine renal arteries were denervated with an irrigated RF catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7d were characterized histomorphometrically and correlated with associated renal norepinephrine (NEPI) levels. NEPI exhibited a threshold dependence on the percentage of affected nerves (%AN) across the range of treatment durations (30–60sec) and power set-points (6–20W). For 15W/30sec treatments, NEPI reduction and %AN tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥four electrodes were powered. Histomorphometry and computational modeling both illustrated that RF treatments directed at large neighboring veins resulted in sub-average 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 RDN efficacy, with increased efficacy at smaller diameters. SUMMARY: Large animal experiments supported by computational and statistical models that account for arterial microanatomy and nerve distribution explain the dependence of RDN efficacy on procedural parameters, e.g. number of electrode treatments, and anatomic parameters, e.g. arterial diameter and the proximity of veins to ablation sites.