Other anatomic and procedural variables, as well as operator experience, do not seem to influence response.
SAN DIEGO, CA—Concordant with studies of other technologies for renal denervation, the presence of untreated accessory arteries was associated with a reduced blood pressure-lowering response to the Paradise ultrasound system (ReCor Medical), an analysis of the RADIANCE-HTN SOLO trial shows.
The effect of denervation was roughly halved when accessories—all smaller than 2 mm in diameter—were not treated, Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), reported here at TCT 2018.
“That suggests, at least to me, that if we’re not able to essentially ablate the nerves in all of the distribution supplying the renal arteries, then we’re getting a less complete denervation and as a result we may have a less efficacious response,” Kirtane told TCTMD.
Richard Heuser, MD (St. Luke’s Medical Center, Phoenix, AZ), who served as a panelist during Kirtane’s presentation, said the findings are not really surprising. “You’ve got to ablate enough of the area, meaning it may not just be ablations in the main renal arteries, but ablations not only in the branches but in the accessories,” he commented to TCTMD. “So I think more is better.”
Learning From SYMPLICITY HTN-3
Evaluating predictors of response to renal denervation has taken on greater importance as the field moves forward following the failure of the SYMPLICITY HTN-3 trial to show that the procedure improves blood pressure control compared with a sham procedure. That setback led researchers and industry to rework their approaches, efforts that have yielded some successes in the form of sham-controlled pilot studies—such as SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and RADIANCE-HTN SOLO—demonstrating that renal denervation can, in fact, reduce blood pressure in hard-to-treat patients with resistant hypertension.
It is known, however, that one-quarter to one-third of patients do not respond to renal denervation, and there are questions about whether that is related to clinical factors, procedural variables, or anatomy.
Kirtane and colleagues explored the issue by looking at data on 71 patients from the renal denervation arm of RADIANCE-HTN SOLO trial who received at least one ablation and had both baseline and 2-month ambulatory blood pressure readings. The trial randomized patients after a 4-week washout period to evaluate the effect of denervation of each main renal artery and suitable accessories in the absence of antihypertensive medication. Accessory arteries larger than 4 mm in diameter were treated, whereas patients with accessory arteries 2 to 3.9 mm in diameter were excluded from the study. Patients with accessories smaller than 2 mm in diameter could be enrolled, but those vessels were not ablated.
The main results of the trial, presented earlier this year at EuroPCR 2018, showed that renal denervation reduced daytime ambulatory systolic blood pressure by 8.5 mm Hg at 2 months, compared with 2.2 mm Hg in the sham arm (P < 0.001). Response was variable, but a greater proportion of patients in the active treatment group achieved a drop of at least 5 mm Hg (66% vs 33%; P < 0.001).
When the investigators looked for predictors of response, the presence of untreated accessory arteries (all smaller than 2 mm in diameter) stood out. On average, this factor dampened the blood pressure reduction by 5.47 mm Hg.
Other key variables, including vessel diameter, vessel length, number of ablations, and operator experience, were not associated with response to treatment.
Highlighting the importance of completeness of ablation, Kirtane reported that the drop in daytime ambulatory systolic blood pressure was about 10 mm Hg in patients who had no accessory arteries and had at least two ablations bilaterally or who had all main and accessory arteries treated, compared with a 4.4-mm Hg reduction in patients with any untreated accessories.
“We know now from randomized trials—robust sham-controlled trials across devices—that renal denervation can lower blood pressure,” Kirtane said during his presentation. “The real question is in whom should we target these therapies and, in some ways, can we modify the procedures and/or procedural screening so as to maximize these benefits, and hopefully in that regard these data are helpful.”
Renal Denervation Back on Track
Kirtane told TCTMD that with these findings in mind, he would expect devices to evolve to be able to ablate some of these smaller accessory arteries.
“We need to refine the procedure further. We need to have devices that allow us to treat the range of renal anatomy that exists. And then, additionally, we need the pivotal trials to enroll and complete to hopefully lead to device approvals and potentially even reimbursement,” he said, noting that pivotal trials having either begun or will soon. “We do know that renal denervation at this point does have a physiologic effect on lowering blood pressure, and for many patients who either want to reduce their medication burden or don’t want to take medicines at all or have adherence issues, that could be very important.”
Anecdotally, the positive results coming out of the pilot studies have spurred more enthusiasm on the part of referring physicians, Kirtane added. “There’s still a long way to go to reverse the negative momentum from SYMPLICITY HTN-3, but at least we’re seeing a little bit of interest resuming.”
Heuser agreed that renal denervation as a field seems to be moving in the right direction.
“I think it’s back on track, because let’s face it, Americans, Europeans, everybody, if they have a one-shot where they can actually treat the problem, they’re going to have that rather than take the pills because they don’t take the pills,” he said.
Note: Kirtane is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.
Kirtane AJ. Procedural and anatomic predictors of response in RADIANCE-HTN SOLO: a multicenter, randomized, sham-controlled trial of endovascular ultrasound renal denervation. Presented at: TCT 2018. September 21, 2018. San Diego, CA.
Kirtane reports receiving institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical.