Key result
Endovascular radiofrequency ablation fails to reliably lower renal norepinephrine, missing targets from asymmetric nerve distribution.
Why the study?
Renal denervation to treat hypertension produces variable results, prompting examination of how renal neural network anatomy affects response to endovascular radiofrequency ablation.
Renal denervation efficacy is highly dependent on the depth and circumferential distribution of periarterial nerves, which are located further from the lumen at the ostium, potentially explaining clinical non-response in trials.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“as suggested by more recent work by investigators at CBSET, Inc. and others, the microanatomic location of these renal nerves and the appropriate application of radiofrequency energy to the renal intimal surface, sufficient to ablate nerves without causing renal injury, remains a significant challenge”
“Very recently, a small study in 12 swines showed that renal sympathetic denervation was unsuccessful in 7 out of 8 cases, since renal noradrenaline levels were not significantly reduced. Successful denervation was only achieved in 1 case, when more than 50% of the nerves were affected”
Variable nerve depth may explain inconsistent renal denervation responses; animal data leave open whether anatomy-guided ablation can improve efficacy.
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.
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Tzafriri et al. (2014) studied Healthy (animal model for renal denervation) (n=12). Endovascular radiofrequency ablation vs. Untreated control arteries was evaluated on Renal norepinephrine (NEPI) levels and nerve ablation efficacy. Endovascular radiofrequency ablation effectively reduced renal norepinephrine in only 1 of 8 treated arteries, demonstrating that procedures not accounting for asymmetric nerve distribution may miss targets.
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