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

Abstract

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.

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.…”

Renal denervation in the era of HTN-3. Comprehensive review and glimpse into the future

“…35 Nerve injury and ablation also appears to be determined by tissue microanatomy at the electrode site, with power density peaking at discontinuities between fatty adventitia and water-rich tissues. 36 The duration of the BP-lowering effect has also been a matter of discussion because there are reports that point to the fact that renal fibers may regenerate and regrow into functionally active nerves. 37 However, studies with long follow-ups (up to 36 months, Table 1) show that BP remains significantly lower than baseline after RDN.…”

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial

“…30 An animal study showed that the ablation zone geometries varied in arc, area and depth, depending on the composition of the adjacent tissue substructure. 31 In addition, the delivered power density was influenced by tissue substructure and peaked at the conductivity discontinuities between soft fatty adventitia and water-rich tissues, not at the electrode-tissue interface. 31 With a greater recognition of nerve distribution, the ablation depth and location should be taken carefully into account.…”