Background - With short radiofrequency (RF) applications, tissue temperature continues to rise after RF-termination ("thermal latency"), which may result in lesion growth after RF-termination. The purpose was to compare in-vivo tissue temperature profile (thermal latency), lesion size and the incidence of steam pop and thrombus between RF-ablation with very-high-power-very-short-RF(90W/4s), high-power-short-RF(50W/10s) and moderate-power-moderate-RF(30W/30s) in a canine thigh muscle preparation and beating heart. Methods - In the thigh muscle preparation (5dogs), a 3.5mm ablation-electrode with 66 or 56 small irrigation holes (QDOT-Micro or ThermoCoolSmartTouch-SF, respectively) was held perpendicular or parallel to the muscle at 10 or 30g contact force (CF). Total of 120RFs were delivered at 90W/4s(QDOT-catheter), 50W/10s or 30W/30s(SF-catheter). Electrode temperature, electrode-tissue-interface temperature and tissue temperatures at 3mm and 7mm-depths were measured. In 6 closed-chest dogs, total of 72RFs were delivered in the ventricle at 90W/4s, 50W/10s or 30W/30s. Results - In the thigh muscle preparation, tissue temperatures and lesion size (depth, diameter and volume) were lowest/smallest for RFs at 90W/4s, followed by 50W/10s and greatest for 30W/30s. Thermal latency (Δtemperature and duration) was greatest for RFs at 90W/4s, followed by 50W/10s and smallest for 30W/30s ( p <0.01). Effective tissue heating (area under curve≥50°C at 3mm-depth) was observed after RF-termination in 88.0±7.6% with 90W/4s, 57.7±14.6% with 50W/10s, and only 31.9±8.5% with 30W/30s ( p <0.01). In beating hearts, lesion size was also smallest with 90W/4s and greatest with 30W/30s RFs. Increasing CF significantly increased lesion depth in all three groups. There was no significant difference in the incidence of steam pop or thrombus between three groups. Conclusions - Tissue temperatures and lesion size (depth, diameter and volume) were lowest/smallest for RF-applications at 90W/4s, followed by 50W/10s and greatest for 30W/30s. The greater thermal latency for 90W/4s RF-applications suggests that a significant portion of lesion is created after RF-termination due to conductive tissue heating.

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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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 peri-arterial ablation. Seven days after multi-electrode 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.

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.