Cynthia Elford had recently lost her left leg to type 1 diabetes, after a sunburned big toe turned nearly black and forced an amputation.
Now, Elford was being told the same thing was happening in her right leg.
"I went to clip the toenail on the big toe of my right leg and I nipped my skin, just nipped it, and it was enough that it didn't heal," said Elford, 63, of Hermitage, Pa. "And it started again, and then it was in two of my toes."
Amputations occur often and quickly for people who have peripheral artery disease (PAD), a narrowing of the arteries that carry blood to the limbs. The slightest wound or ulcer can turn gangrenous if there's too little blood flow to promote healing.
But Elford still has her right leg, thanks to an experimental, minimally invasive procedure called "LimFlow."
The LimFlow procedure allows doctors to convert a vein into a new artery that will supply fresh blood flow to the afflicted leg.
Three out of four patients (76%) who underwent the procedure wound up keeping their leg, with their wounds either healed or healing, according to new clinical trial results published March 30 in the New England Journal of Medicine.
Elford was the first person in Ohio to undergo the LimFlow procedure, back in April 2018. Five years later, she is healed and pain-free.
"These are patients that would have undergone otherwise a major amputation and would have lost a leg below the knee or above the knee," said lead researcher Dr. Mehdi Shishehbor, Elford's doctor and president of the University Hospitals Harrington Heart & Vascular Institute, in Cleveland. "It gives me joy that we were able to save these limbs from being amputated."
The LimFlow procedure is expected to offer fresh hope to so-called "no-option" patients with leg artery blockages that cannot be treated either by an arterial bypass or by opening up the artery with a stent, Shishehbor explained.
Bringing fresh blood to legs
"About 20% to 30% of the time, unfortunately, the disease is so severe and so calcified that neither bypass nor endovascular approach can work for these patients," Shishehbor said. "When I see these patients, the hardest thing for me is to tell them, I'm sorry, we cannot improve blood flow for you. The only thing left is a major amputation."
Risk factors for these blockages — which doctors call chronic limb-threatening ischemia — include peripheral artery disease, chronic kidney disease, high blood pressure and elevated cholesterol.
"The big picture is there are 200 million patients worldwide with peripheral arterial disease," said Dr. Sanjay Misra, an interventional radiologist with the Mayo Clinic, in Rochester, Minn. "It's estimated that 1 million Medicare beneficiaries have critical limb ischemia, and 20% don't have any good option."
About 185,000 amputations occur in the United States each year, and an estimated 3.6 million people are expected to be living with limb loss by 2050, according to background notes on the study.
"There are about 500 major amputations that are happening every day in the United States," Shishehbor said. "Every day, 500 patients are losing their leg. And these are the patients who are no-option patients."
Arteries are the blood vessels that carry oxygenated blood and nutrients from the lungs and heart to all the body's tissues and muscles. Veins carry the spent blood back to the lungs to be re-oxygenated.
In the LimFlow procedure, surgeons run one catheter down the blocked artery that's causing the problem, and a second catheter up a nearby vein intended to serve as a new artery for the leg.
The two catheters work in concert to run a stent from the blocked artery over to the vein, essentially converting the vein into a replacement artery.
The patients are sedated but not knocked out by general anesthesia during the procedure, and can go home the next day, Shishehbor said.
"I was foggy but could hear things," Elford recalled of her procedure. "When he got it through, his nurse came running up to the side of me and said, 'It's OK. He's got it. It's done.' And I could hear everybody clapping and yelling and hooting. It was like a circus in there."
For the clinical trial, researchers recruited 105 "no-option" patients like Elford to undergo the procedure at 20 medical centers across the United States.
Doctors successfully completed the procedure in all but one of the patients. Six months after the procedure, 76% of patients had kept their leg, the researchers said. In addition, wounds completely healed in 25% of patients, and were in the process of healing in 51% of patients.
"It's not a home run for everybody, but gosh, look at the numbers, right?" Misra said. "This study enrolled those at the highest risk for amputations. Those numbers are very high compared to other studies in this space. This is a very sick population."
The researchers were also surprised to find that, in some patients, the restored blood flow even promoted the creation of new capillaries and smaller arteries, Shishehbor said.
"We have data that the blood flow seems to be significantly improved, even though the bypass may close after six months or one year or a year and a half," Shishehbor said. "That's something we are still studying and trying to understand. How is that once we create this, something physiologically is changing in the patient's foot that's allowing the blood flow to improve?"
In addition, side effects were minimal, Shishehbor said.
Since the procedure reversed the blood flow in a vein, researchers suspected some swelling might occur due to fluid accumulation, Shishehbor said.
But there were enough other veins running from the patients' feet that widespread fluid retention didn't happen, he added.
"Humans have thousands of veins, so we only take one of those veins in the lower foot and reverse the blood flow," Shishehbor said. "There are multiple other veins that can still take the blood that has been used and return it back to the heart and lungs. So, we don't see any major complications from this."
Not that recovery doesn't hurt, Elford said.
"They told me, just remember, you're going to have a lot of pain," Elford said. "It's going to be different than the kind of pain you had, but you have to just hang on and be patient because it'll work its way out. Your body has to get used to the things that have been changed in your body."
Tough recovery, but worth it
"It was awful. It was really awful," Elford added. "It's not easy to get through, but do you want to live your life without the leg, or do you want to go through some pain and see the results I've seen?"
LimFlow currently is under review with the U.S. Food and Drug Administration, based on the results of this clinical trial, Shishehbor said. The trial was funded by LimFlow, the company that created the procedure.
"This is now in the hands of the FDA, and we are hoping that we will get approval soon and that this technology will be available widely across the United States in appropriate centers with appropriately trained operators," Shishehbor said. "Obviously, this is a technically challenging procedure and we need to teach operators how to perform it."
In the meantime, researchers are expanding the number of experimental centers from 20 to 40, so that more patients will have access to the procedure, Shishehbor said.
"I can tell you I've been looking at this for several years, bringing it to Mayo Clinic, Rochester, speaking to my surgeons," Misra said. "It's become very manageable and easier to do in the right patient with the right anatomy."
Misra noted that patients will have to be carefully screened. For example, people with high blood pressure in their veins might not do as well.
Those who undergo the procedure will also need to be patient afterward, and should not expect wounds and sores to immediately start healing.
"Making the artery backfill the vein where the wound is and perfusing it from the back door, it does take time," Misra said. "The wounds may not look as good as you want early on."
It's also still an open question whether this could be offered at smaller hospitals, or if only large medical centers will be able to care for patients with these sort of severe complications, Misra added.
"How much of this can be made available to small hospitals everywhere will be a debate," Misra said. "But I think it gives us some new options for patients who are going to lose their legs if we don't do anything."
For her part, Elford is managing to keep up with her three active grandchildren using her good right leg and her prosthetic left leg.
"I mean, I'm free to go about myself, right?" Elford said. "I would recommend it. It's not easy to get through, but I have my leg."