Innervation Patterns May Limit Response to Endovascular Renal Denervation

Abstract

BACKGROUND Renal denervation is a new interventional approach to treat hypertension with variable results. OBJECTIVES The purpose of this study was to correlate response to endovascular radiofrequency ablation of renal arteries with nerve and ganglia distributions. We examined how renal neural network anatomy affected treatment efficacy. METHODS A multielectrode radiofrequency catheter (15 W/60 s) treated 8 renal arteries (group 1). Arteries and kidneys were harvested 7 days post-treatment. Renal norepinephrine (NEPI) levels were correlated with ablation zone geometries and neural injury. Nerve and ganglion distributions and sizes were quantified at discrete distances from the aorta and were compared with 16 control arteries (group 2). RESULTS Nerve and ganglia distributions varied with distance from the aorta (p < 0.001). A total of −75% of nerves fell within a circumferential area of 9.3, 6.3, and 3.4 mm of the lumen and 0.3, 3.0, and 6.0 mm from the aorta. Efficacy (NEPI 37 ng/g) was observed in only 1 of 8 treated arteries where ablation involved all 4 quadrants, reached a depth of 9.1 mm, and affected 50% of nerves. In 7 treated arteries, NEPI levels remained at baseline values (620 to 991 ng/g), ≤20% of the nerves were affected, the ablation areas were smaller (16.2 ± 10.9 mm2) and present in only 1 to 2 quadrants at maximal depths of 3.8 ± 2.7 mm. CONCLUSIONS Renal denervation procedures that do not account for asymmetries in renal periarterial nerve and ganglia distribution may miss targets and fall below the critical threshold for effect. This phenomenon is most acute in the ostium but holds throughout the renal artery, which requires further definition.

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

“…[21][22][23] This study strongly suggests that renal sympathetic nerves attempt to regenerate but without apparent functional reconnection based on persistent NE level suppression. 14,[24][25][26] The high degree of distal nerve atrophy observed at 7 and 30 days in this study reported at chronic time points in other large animal experiments where RF ablation of renal nerves was performed. 14,20 It is necessary to further establish if the apparent morphological "recovery" of distal nerves could be responsible for the late increase in NE levels and whether this partial recovery may or may not produce a physiologic increase in blood pressure.…”

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension

“…Similarly, the results of later animal studies cast doubts upon the lasting effect of catheter-based RDN when reinnervation was proved even after 5.5 months. 24 The total number of ablations 25 or even treatment locations 26 are discussed to improve the efficacy. However, evidence of the long-lasting effect of RDN, as well as evidence of better efficacy of multielectrode systems, is lacking.…”

Renal Sympathetic Denervation: Hibernation or Resurrection?

“…The first study found that only 40% of the sympathetic fibers course within 2 mm from the lumen whereas 30% are found between 4 and 9 mm from the lumen [8], too far to be reached by low-energy radiofrequency ablation. The other study reported a segment-related distance from the lumen, with 75% of the sympathetic fibers situated within 3.4 mm from the lumen at the distal segment of renal arteries and within 9 mm from the renal artery wall at the proximal segment [9]. Further studies indicate that fibers in the renal artery branches are much more proximal to the lumen and perhaps more approachable by transcatheter techniques.…”