Procedural and Anatomical Determinants of Multielectrode Renal Denervation Efficacy.

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.

Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation.

BACKGROUND: The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. METHODS AND RESULTS: A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (P<0.001 for circumference; P=0.003 for thinning). Severe collagen damage such as denatured collagen was also significantly less in the irrigated compared with the conventional radiofrequency group (P<0.001). Nerve damage although not statistically different between the irrigated radiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (P<0.001). CONCLUSIONS: Saline irrigation significantly reduces arterial and periarterial tissue damage during radiofrequency ablation, and there is a trend toward less nerve damage.

Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension.

Renal denervation (RDN) is a treatment option for patients with hypertension resistant to conventional therapy. Clinical trials have demonstrated variable benefit. To understand the determinants of successful clinical response to this treatment, we integrated porcine and computational models of intravascular radiofrequency RDN. Controlled single-electrode denervation resulted in ablation zone geometries that varied in arc, area, and depth, depending on the composition of the adjacent tissue substructure. Computational simulations predicted that delivered power density was influenced by tissue substructure, and peaked at the conductivity discontinuities between soft fatty adventitia and water-rich tissues (media, lymph nodes, etc.), not at the electrode-tissue interface. Electrode irrigation protected arterial wall tissue adjacent to the electrode by clearing heat that diffuses from within the tissue, without altering periarterial ablation. Seven days after multielectrode treatments, renal norepinephrine and blood pressure were reduced. Blood pressure reductions were correlated with the size-weighted number of degenerative nerves, implying that the effectiveness of the treatment in decreasing hypertension depends on the extent of nerve injury and ablation, which in turn are determined by the tissue microanatomy at the electrode site. These results may explain the variable patient response to RDN and suggest a path to more robust outcomes.