“There is a lack of safety data about morphological changes in the renal arteries after renal denervation. With regard to how bad radiofrequency is for the renal arteries, honestly speaking, we do not know at this time, but there are more than theoretical concerns about safety,” Jilek said. He was referring to a concern expressed within the interventional community about the risk of damage to renal arteries during delivery of radiofrequency energy.
The renal denervation procedure involves the interventionalist using a steerable catheter with a radiofrequency energy electrode tip. The heated tip (at 60° Celsius) is put at the renal artery wall to disrupt the nerves. “Is putting a hot tool into the renal artery, a safe procedure?” Jilek said.
What data do we have on safety?
“What we have is the SYMPLICITY HTN-I trial where 45 patients were treated with renal denervation. There is post-procedure imaging of the renal arteries after 6 months available for 31% of these patients, and one irregularity was noted in a side-branch. In the SYMPLICITY HTN-2 trial, 49 patients were treated and there was follow-up imaging of the renal arteries by MRI or CT for 20% of the patients and ultrasound imaging data for 75% of the patients.” One progression of atherosclerosis was seen, noted Jilek, who also questioned the use of sonography as the correct imaging modality to be used.
“We also have to be aware that the way the results were reported was changed; in the first publication all irregularities were reported, but in the second publication only stenoses over 60% at the lesion site were reported. So we do not know if there were any cases of atherosclerosis up to 60% of the renal artery. “There is a lack of safety data. In a small cohort with insufficient follow-up, stenosis of greater than 60% occurred in 1.4% of the patients,” Jilek said, adding that data was expected from the Global Symplicity Registry (5,000 patients) and the SYMPLICITY HTN-3 trial (530 patients).
Jilek then turned to experimental work in animals to consider the morphology of the acute lesions, the fibrosis of the chronic lesions and the effectiveness of chronic lesions. “Our animal lab study of pigs showed the renal artery without any irregularities of the renal artery before performing renal denervation.
“In the acute phase small irregularities of the renal artery were seen and thrombus formation at lesion sites. Ten days post-treatment irregularities have resolved and thrombus was absent. The conclusion is to preceed with heparin administration and platelet inhibition during and after renal denervation procedure.”
Jilek cited a second animal trial that looked at chronic lesions, six months after renal denervation. Imaging of the renal artery showed that there was a large area of fibrosis in the media and a small fibrosis in the adventitia. Jilek said, “The study showed that we have an induction of fibrosis in the media. So the question is why do we target the media if we want to target the nerves in the adventitia? Why do we ablate a structure that is not our target structure?” He did, however, clarify that six months after the procedure, there were no inflammatory cells in the fibrosis, which indicated that the fibrotic process should have ended.
A third aspect to consider in the study, said Jilek, was that there were perivascular nerves still functioning in the ablation spots. In the subacute setting after 10 days, there are some nerves that remain functioning and they are located in the outer adventitia. So far, we do not know how many nerves we have to ablate. Do we have to reach a complete renal denervation or is it sufficient to reduce the number of afferent nerves? This might mean that the lesion depth of conventional radiofrequency does not seem appropriate for nerves in the outer adventitia,” he said.
Irrigated vs. non-irrigated radiofrequency ablation
Jilek proposed that the use of irrigated radiofrequency ablation might overcome some of the three problems discussed, as learned from lessons in endocardial ablation. In this procedure, the same energy is used, but the electrode tip is cooled down to 43° celsius. Histology from a study that compared the two types of radiofrequency (irrigated vs. non-irrigated) in endocardial sites shows that there is less injury to the endothelium when irrigated radiofrequency ablation is used. So in left atrial ablation procedures, irrigated ablation is the standard,” he said, but he added “that we have to consider the different tissue characteristics of cardiac and of renal artery tissue”.
“Non-irrigated radiofrequency lesions are covered with thrombus or char formation in the acute ablation setting. Nerves in the outer adventitia may not be effectively ablated with non-irrigated radiofrequency and irrigated radiofrequency may be an alternative energy. Whether the use of irrigated radiofrequency results in a reduction of clinical endopoints is unknown,” Jilek concluded.