Study Suggests That Local Tissue Anatomy May Explain Variable Patient Responses to RDN Therapy

May 4, 2015—CBSET, a not-for-profit preclinical research institute, announced that its scientists have published data and analyses that provide critical insights into the predictability, variability, and treatment success of catheter-based renal denervation (RDN) therapy. These data suggest that new, optimal alternative devices compared to first-generation RDN systems may enhance or assure efficacy, stated CBSET.

The study, “Arterial Microanatomy Determines the Success of Energy-Based Renal Denervation in Controlling Hypertension,” was published by Abraham Rami Tzafriri, PhD, et al in Science Translational Medicine, a publication of the American Association for the Advancement of Science (2015;7:285).

As summarized in Science Translational Medicine, the investigators conducted the study to understand the determinants of successful clinical response to RDN. They integrated porcine and computational models of intravascular radiofrequency RDN. 

The investigators reported that 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. 

They found that at 7 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, concluded the investigators in Science Translational Medicine.

"Though a large body of scientific research has convincingly demonstrated the link between sympathetic activity and hypertension, catheter-based RDN has been confounded by unreliable efficacy in some late-stage clinical trials," commented study coinvestigator, Felix Mahfoud, MD, in the CBSET press release. "The published data have demonstrated that anatomical asymmetries along the length and circumference of the renal artery can limit the efficacy of ablation therapies in the treatment of resistant hypertension. These data increase our insight into the connection between target anatomy and patient efficacy post-RDN by single and multiple radiofrequency electrode catheters." Dr. Mahfoud, who is from the Department of Internal Medicine III at Saarland University is Homburg/Saar, Germany, serves as co-course director for EuroPCR.

"Conflicting data from recent clinical trials must not deter the community. Sympathetic denervation and neuromodulation techniques still provide an exciting opportunity for the treatment of diseases with increased sympathetic tone, such as hypertension and of a variety of other cardiovascular diseases," Dr. Tzafriri, who is CBSET's principal scientist and a computational modeling expert, advised in the announcement. "The current device therapies are still in their infancy, and the rate of technological advancement in this field is accelerating exponentially. These preclinical data help explain the prior clinical variability documented following RDN in humans and illustrate that electrode irrigation can protect the artery wall during efficacious ablations without diminishing ablation area in the nerve rich periarterial compartment."

Lead investigator Elazer Edelman, MD, who is chairman and cofounder of CBSET, added, “Mechanistic insight bridges the preclinical and clinical experiences and is in the end the only effective means of resolving seeming conflicts or disparities in observations. CBSET’s groundbreaking work in RDN has provided the precision needed to produce a coherent paradigm by which to appreciate this complex field. The systematic integration of quantitative computational-modeling with rigorous preclinical evaluation has now created a framework by which to optimize the potential of sympathetic denervation and modulation as a treatment modality.”