Deep venous arterialization: An alternative for ‘no-options’ patients with severe CLI
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Key takeaways:
- Transcatheter arterialization of the deep veins is safe and can be successfully performed in patients with severe critical limb ischemia.
- The technique could improve race-based disparities in care.
About two-thirds of adults with severe critical limb ischemia treated with a transcatheter deep venous arterialization system achieved amputation-free survival at 6 months, according to data from the PROMISE II trial.
In the single-arm PROMISE II study, researchers used a novel system (LimFlow) designed to divert arterial flow from the tibial artery to the tibial veins. As Healio previously reported, the study included 105 participants (mean age, 69 years; 69% men) with “no-option” CLI and Rutherford class 5 or 6 who underwent deep venous arterialization; stable patients on dialysis were eligible. The primary endpoint was amputation-free survival at 6 months, with a performance goal of 54% based on prior literature.
The findings exceeded researchers’ expectations. Technical success was achieved in 99% of procedures and the primary endpoint was met in 66% of patients (posterior mean, 0.66; 95% Bayesian credible interval, 0.565-0.745; P = .005). Limb salvage was attained in 67 patients (76% by Kaplan-Meier analysis). Wounds were completely healed in 25% of participants and were in the process of healing in 51% of participants.
“With this study, we are now providing significant hope for these patients,” Mehdi H. Shishehbor, DO, MPH, PhD, president of University Hospitals Harrington Heart & Vascular Institute, Cleveland, told Healio. “We are showing that in these ‘no-options’ patients, we are technically successful 99% of the time and we are able to save their limbs 76% of the time.”
Healio spoke with Shishehbor about the rigorous PROMISE II study protocol, how LimFlow works, and how the novel technique could be deployed to improve race-based disparities in CLI.
New data from PROMISE II were first reported at VIVA 22. The study findings were published Wednesday in The New England Journal of Medicine.
Healio: What is the outlook typically for these patients with severe critical limb ischemia?
Shishehbor: For patients with CLI — those with ulcers and gangrene — they are at risk for amputation. These are people with diabetes with significant calcification, who have significant distal tibial disease and small vessel disease. Currently, for these patients, there are two options available to improve the blood flow to prevent amputation. One option is surgery — bypass. The other option is endovascular. Unfortunately, because of the complexity of the disease, we cannot help these patients 20% to 30% of the time with either approach. We call these patients “no-options” patients. The only option they have is below-the-knee or above-the-knee amputation. We call them “no options” because we do not consider amputation an option. These are people who have been told there was nothing available to them.
The current standard of care is bypass or endovascular, as I mentioned. However, those procedures require us to be able to find a target in the foot to bypass the blockage. In diabetes, there is often no target, nowhere to go. The arteries are so calcified, with blockages 30 cm or 40 cm long, that we cannot cross them with wires and balloons. Going after these arteries is futile.
This made us wonder: Is there another system that could allow us to deliver oxygenated blood to the distal tissue in the foot?
Healio: How does LimFlow work?
Shishehbor: We know the veins are not as affected in diabetes. We thought, why don’t we take the blood flow in the artery, divert it into the veins in the lower leg, in the calf, and reverse the blood flow in those veins to get oxygenated blood in the distal foot to the veins. We take the veins that are supposed to bring the blood back to the heart, reverse the blood flow through this procedure, and divert oxygenated blood from the tibial arteries in the calf into the tibial veins. This makes the veins carry oxygenated blood down the foot in reverse order.
Healio: Did the findings of PROMISE II, these limb salvage numbers, surprise you?
Shishehbor: When we initiated this study, we knew that these were very sick patients who would otherwise undergo an amputation. Going in, I thought that even if there was 10% limb salvage, that is one out of 10 people where we can save their leg. When we saw 76% at 6 months and 99% technical success with a novel procedure that is technically challenging, I was dumbfounded, to be honest with you. I could not believe this success rate for the sickest of the sick.
Some may say “no options” is in the eye of the beholder. For this trial, the FDA mandated that a multidisciplinary team review every single case. A panel of experts had to reach a consensus that these were patients truly with no other options after reviewing the angiograms. This was a multidisciplinary team of doctors that reviewed each case. Every patient had to be approved by an independent committee of experts; this was not the investigators making the decisions. That is an important point.
Healio: You mentioned that this procedure is technically challenging. Where do you and your colleagues go from here? This procedure is not currently FDA-approved in the United States, so what are the next steps?
Shishehbor: We are optimistic because of our technical success rate. The 20 sites that participated in PROMISE II were advanced operators. We feel that once this is approved, we can educate and train operators to perform this procedure safely. We have gained a lot of knowledge through PROMISE I and PROMISE II. Now, we can share that knowledge with new operators who will be learning this technique.
Currently, the device is not FDA-approved. The company has initiated a new research project, PROMISE III. This is a registry of 25 sites in the United States, and University Hospitals is one, that will allow about 200 patients to still enroll and undergo this technique. We did not want patients to miss this opportunity while we await FDA approval. We are pleased the FDA has permitted us to continue with this new registry.
Healio: In this cohort, more than half of participants were Black or Hispanic. Can you talk about the race disparities among patients with severe CLI? What could that mean for improving disparities with this novel technique?
Shishehbor: Amputation has significant disparities associated with it. African American and Hispanic adults are four times more likely to undergo amputation and four times less likely to undergo revascularization. They are also the people who show up in the later stages of disease, often due to inability to access care and other factors. They are unable to receive the care they need early in the disease. When they present, they are more likely to be a “no-options” patient. This is an underserved population. In PROMISE II, almost 50% of participants were from underrepresented backgrounds, and they had successful outcomes. This limb-saving technology will hopefully help us to close this disparity gap.
Healio: Anything else you would like to mention about this study?
Shishehbor: It is important that we do not take amputation lightly. Amputation should be a last resort. When a patient has exhausted all their options, I hope clinicians consider second and third opinions, and look to these sites that offer these cutting-edge technologies like LimFlow so patients can avoid amputation. Now, we have evidence that a transcatheter deep venous arterialization system offers hope and opportunity.
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For more information:
Mehdi H. Shishehbor, DO, MPH, PhD, can be reached at mehdi.shishehbor@uhhospitals.org; Twitter: @shishem.
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