Experts Discuss Future of Renal Denervation

MIAMI BEACH, FLA.—Renal denervation was the focus of discussion during two presentations at TCT 2012. One presenter reviewed novel devices in the field, while another focused on new targets for the therapy.

Radiofrequency catheters, balloons and more

Horst Sievert, MD, PhD, of the CardioVascular Center in Frankfurt, Germany, reviewed new catheter-based technology alternatives for renal denervation, including radiofrequency catheters and balloons, drugs, radiation and ultrasound — many of which are approved in other countries but have yet to receive approval in the United States. According to Sievert, 60 companies are currently working on new renal denervation devices.

Initial trial data show that St. Jude Medical’s EnlighHTN renal artery ablation catheter, which has a 90-second per electrode ablation time, provides a rapid treatment effect that is comparable to Symplicity (Medtronic). Medtronic has completed its first-in-man study (n=9) of its radiofrequency, multi-electrode device.

Additionally, an initial study (n=8) showed that Covidien’s OneShot balloon-based catheter reduced systolic BP from 185.7 mm Hg at baseline to 143.7 mm Hg at 6 months (P=.006).

In terms of drugs, ApexNano has a device in which nanoparticles are injected into the renal artery and pulled into the renal artery wall by a magnetic field using different methods. Mercator MedSystems is developing a catheter-based system that allows for the injection of drugs into the renal sympathetic nerve sheath. Swine models have also shown that the drug vincristine can reduce the number of nerves in the renal artery.

Radiation also is being applied to renal arteries with the idea that nerves are more sensitive to radiation than any other tissue. Early data for this treatment are positive as well, Sievert noted.

Ultrasound, in the form of Recor Medical’s ultrasound transducer has shown reductions in BP at 6 and 12 months, he added. Cardiosonics is another system that uses high-intensity ultrasound to reduce kidney tissue norepinephrine and destroy nerves. Additionally, the first-generation Kona Medical Surround Sound System is an external ultrasound that tracks the target and delivers ablative ultrasound energy, while the second-generation is a fully noninvasive system that uses ultrasound for targeting and tracking—a feature that may “bring interventionalists out of the business,” Sievert said.

Efferent or afferent?

In the same vein, Paul A. Sobotka, MD, of The Ohio State University, Columbus, addressed future prospects for renal denervation therapy, highlighting the debate on whether reduction of renal sympathetic efferent or afferent signals is considered desirable, noting that the optimal dose of reduction of either is unknown and may vary by patient populations and clinical endpoints.

The disease state targets based on the efferent hypothesis involve congestion related to the rightward shift of pressure natriuresis curve and the generation of aldosterone; complications of renin-angiotensin-aldosterone activation; and consequences of excessive sympathetic signaling. The afferent hypothesis, however, is much more complicated, as clinical data suggest the kidney communicates with the brain, which is predicated on the kidney housing an enormous number of both mechanosensors or chemosensors.

“The vision of endovascular procedures for renal denervation really begins to speak of targeting two different physiologies protecting a single organ from the ravages of excessive sympathetic stimulation, such as protection of the kidney or protection of the heart or reducing central sympathetic drive by the selective reduction of a single organ’s contribution to that excessive drive that the brain sees and then meets in the multiple organs across the body,” Sobotka said, noting that perhaps we have not yet arrived at the optimal solution for renal denervation.