“Years ago, before the development of hypertension medications, the only thing medical science could offer patients with lethal levels of hypertension was surgery to cut the sympathetic nerves in the kidneys,” Mendelsohn says. “No one really understood how it worked, but it did. However, it was difficult to find the right place to cut, and too often nerves controlling the bladder, bowel and sexual organs were damaged. With the advent of hypertension medications, the surgery was no longer done.
“I often see patients with hypertension that is difficult to control, even with multiple medications. Compliance isn’t always easy. There are side effects. Sometimes, even with the best efforts, some patients are still at risk for stroke and damage to their heart and other organs.
“Since we can do so much with RV ablation in the heart, it had occurred to me that a similar approach might give us more precision in ablation of the sympathetic nerves in the kidney that affect blood pressure. I had begun searching the literature to identify the location of the nerves that influence blood pressure and found that very little work had been done in that area. So mapping those nerves became a research project. One of our residents and a pathologist at Princeton did five cadaver studies to trace them. We compiled the data and had a good sense of where the nerves lay along the renal artery and how deeply energy would have to penetrate to be effective.
“As Cohen and I talked, he mentioned that he had met with several advisors looking for suggestions of other applications for his technology and asked what I thought. I told him to send me the details about his design and I’d get back to him.
“After studying the design, I called him and asked whether he had considered using it for renal nerve ablation to treat hypertension. He agreed it could probably be used in the renal artery, but said ‘no one knows where the nerves are.’ I told him, ‘I do. It’s in a study I haven’t published yet.’ He didn’t say anything for about ten seconds, then said ‘Get on a plane and bring your data.’”
Mendelsohn flew to California and met with Cohen at Minnow Medical. “We pulled out a white board and started drawing, plotting where on the balloon we’d need to place electrodes to have them in the optimal position,” Mendelsohn says. “We also added temperature controls. The question was whether we could get the energy deep enough to be effective. Using a prototype and tweaking it in about 100 animal studies, we found that the answer was yes.”
The next step was human trials in Europe. The Rothschild group in Paris was the lead investor of a venture capital group that funded the trials. They suggested changing the name of the company, since Minnow Medical had an X-rated connotation in French.
“So, as Vessix Vascular, they began the European trial of 150 patients,” Mendelsohn says. “They responded so well, we saw blood pressure numbers improving in the neighborhood of 30 mm. We were delighted and the company received certification to market the device in Europe. It was going to take a much larger company with more resources to commercialize the device in the U.S., gather data, and get it through the process of FDA approval. About 16 months after Rothchild made its investment, the company sold for several times that amount to Boston Scientific.
“Eight to ten lead investigators across the country will be involved in the randomized REDUCE-HTN: REINFORCE trial of the device. Since I was there from the beginning, and my partners at Cardiology PC and research staff have been very involved, they knew we could get up and running quickly, so they chose us to perform the first US procedure. Our team mobilized quickly. They have been remarkable. One of my partners, Michael Wilensky M.D, referred the first patient. It isn’t just me. It’s our entire team working together.
“It’s a thrill for me to see this device through from that whiteboard drawing to the first patients. We’ve done four procedures now. Since it’s a randomized trial, we won’t be able to release data until all 100 procedures have been completed and all the patients are seen for their eight-week follow-up. However, I’ve very optimistic that we will see results comparable to the response we saw in Europe.
“If so, FDA approval should follow, and it shouldn’t take long to train cardiologists who are accustomed to doing other catheter procedures. One thing that is especially nice about the design is how user-friendly it is. Once the catheter is positioned in the renal artery just before the branch, you simply inflate the balloon and the electrodes should be in the right position. Turn it on for 30 seconds, then go to the other kidney. A procedure that takes half an hour or less could change a patient’s life forever.”
Why selective denervation of the renal sympathetic nerves works is still not well understood. It may be related to feedback to the brain related to fluid retention and stimulation of hormones. However, this new, more precise approach to an old strategy could dramatically change how persistent hypertension is treated in the near future.
Since their chance meeting at a medical conference and working together to develop the device,
Mendelsohn and Cohen have become good friends.
“Raymond is a wonderful guy, and he has a soft heart,” Mendelsohn said. “One of the doctors who helped us with the European trial was from Australia. He had a patient who was only 12 and despite all medications his blood pressure was still over 250. Since the device we’re testing is sized for adults, he called Raymond to see if anything could be done. Raymond and his engineer went in the lab and built a smaller version and shipped it off to Australia. They probably saved the child’s life.”