“I am going to give you reasons to be excited about your critical limb practice,” Peter Schneider (University of California San Francisco, San Francisco, USA) told delegates attending the International Symposium on Endovascular Therapy (ISET; 9–11 May, Miami, USA), in a talk focusing on innovative tools on the horizon for the treatment of chronic limb-threatening ischaemia (CLTI). “I think critical limb ischaemia has come to the forefront of our practices and of community awareness, and finally now the tools are starting to show that,” he opined.
Covering developments in assessment (including monitoring, perfusion, and wound evaluation), reconstruction, and medication delivery, Schneider left his audience with an optimistic outlook for the future of CLTI treatment.
Assessment: Wearables, implantables, and artificial intelligence
Turning first to wearables and implantables, which he said “are just around the corner”, Schneider expanded: “[In terms of] implantables, there is a patent application for a stent with a sensor on it, which of course makes sense that someday that is how we will be doing our surveillance.
“Wearables are available now, and are essentially a transfer from other types of technology.” Citing a JAMA Network Open article from late 2020, which looked at the association between wearable device–based measures of physical frailty and major adverse events following lower extremity revascularisation, Schneider said he expected to see “more articles like this one”, adding: “I am sure we are going to have [investigations into the use of wearable devices to assess frailty] for claudication patients on a regular basis as well.”
In addition to wearables and implantables, he also directed the ISET audience’s attention towards the use of artificial intelligence (AI): “A couple of companies have taken it upon themselves to do a digitised wound evaluation, and then use AI to help the programme get smarter over time about identifying the cause of the wound and the progress of the wound. So much of what we are doing is an inexact science: when we think of screening, population management, treatment guidelines, we are thinking about the population as a whole, and just trying to do the right thing, but each of these patients comes having their own code and their own set-up, so the transfer of existing technology I think will help us to individualise the way we would like to.
Reconstruction: Modified balloons, new implants, alternative bypass, below-the-ankle angioplasty
“Below-the-knee [BTK] angioplasty is just sitting there waiting for us to really develop it,” Schneider stated, telling delegates listening in Miami and online that the medical community is now starting to see data showing improved wound healing. However, he noted that the patency data are “still unclear”, and in his opinion needs to be further assessed. “But I think we are really developing [in this arena],” he concluded.
The speaker first highlighted the lithotripsy with Shockwave. Lithotripsy waves travel outside the balloon, and disrupt both superficial and deep calcium. It is a way to improve vessel wall compliance prior to controlled, low pressure dilatation. “The question is how valuable is this going to be in BTK interventions?” Schneider asked. “I think it remains to be seen, but it certainly is a technology for interrupting calcium.”
Another technology Schneider considered was serration angioplasty. Noting his conflict of interest due to his involvement with Cagent Vascular, a developer of serration technology for vessel dilatation in endovascular interventions, Schneider explained how the novel Serranator percutaneous transluminal angioplasty (PTA) serration balloon catheter works: “The idea is that you poke little holes in the artery, and allow a stress relief line along the vessel so that it can be opened. I really believe that BTK angioplasty is due for a makeover by one method or another, and here is just an example of the flexibility of this tool.” The Serranator PTA serration balloon catheter is the first and only angioplasty balloon to receive Food and Drug Administration (FDA) approval and the CE Mark that embeds serration technology into a semi-compliant balloon for treating peripheral arterial disease (PAD). Earlier this year, results of Cagent Vascular’s PRELUDE-BTK study—a prospective, single-arm, multicentre feasibility study investigating the safety and efficacy of serration angioplasty—were presented at the Leipzig Interventional Course (LINC; 25–29 January, online).
Forty-six patients were treated with the Serranator device and 53 lesions were analysed by the core lab. The average final residual stenosis was 21.8%, with an average BTK arterial lumen gain of 1.55mm. These results were achieved with a low average maximum atmospheric pressure of six atmospheres. The bailout stent rate was 1.9%. A subset of lesions (n=10) were imaged with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) and analysed by a core lab. All showed a serration effect. At 30 days, the freedom from primary safety events was 95.7%. Freedom from clinically driven-target lesion revascularisation (TLR) was 97.7%, and there were no serious adverse events related to the device.
Following this discussion on modified balloons, Schneider turned to a new method of post-angioplasty dissection repair: focal dissection repair. He showcased a new implant, the Tack endovascular system (Intact Vascular), the first FDA-approved vascular implant for BTK post-angioplasty dissection repair. Regulatory approval for the device was based on data from Intact Vascular’s Tack optimised balloon angioplasty II BTK (TOBA II BTK) clinical trial, which met all primary endpoints with 100% acute dissection resolution. The TOBA II BTK results demonstrated 95.7% amputation-free survival, 87.3% target lesion patency, with significant improvement in toe-brachial index (TBI), and 92.0% freedom from clinically-driven reintervention at six months.
Schneider mused: “The issue is; do we need IVUS? We know IVUS is more sensitive—all of the trials we did with focal dissection repair were angiographically-driven, however, could the results have been better if we used IVUS routines? Just something to think about as BTK disease gets more sophisticated, what will the role of IVUS be?”
Another implant Schneider explored in his presentation was a bioabsorbable vascular scaffold, the Abbott Esprit. This is an everolimus-eluting device, designed for the superficial femoral artery and iliac arteries. Recently-published data from Ramon Varcoe (Sydney, Australia) and colleagues show “excellent” patency out to five years. The LIFE-BTK randomised controlled trial, where participants will be randomised 2:1 Esprit versus PTA, is now enrolling in the USA.
Lastly in the “reconstruction” portion of his talk, Schneider mentioned percutaneous bypass. “The mean lesion length in the PQ bypass trial is in excess of 30cm, so we have not typically had an option for lesions of that length using percutaneous devices,” he announced. DETOUR II is a prospective, multicentre trial evaluating the Detour system for percutaneous femoral-popliteal bypass in patients with extremely long, complex lesions in the SFA. The study enrolled 202 patients in 36 sites in the USA and Europe, and is assessing freedom from major adverse events (MAE) within 30 days of the index procedure as the primary safety endpoint. The primary effectiveness is primary patency at 12 months.
Speaking to Interventional News about the potential of percutaneous bypass, principal investigator Jihad Mustapha (Advanced Cardiac and Vascular Centers, Grand Rapids, USA) said at the end of 2020: “If percutaneous femoral-popliteal bypass is shown to be safe and effective, similar to the outcomes demonstrated in DETOUR1 study, it could be a game changer for the way we treat complex, long-segment SFA disease today.”
“We do not have any paclitaxel BTK drug-coated balloons (DCBs) in the USA,” Schneider said. While he noted that there are several paclitaxel DCB trials currently underway in the USA—he showed three of them: IN.PACT DEEP, Lutonix BTK, and BIOLUX P-II—he commented that “nothing is close to being approved”, though some show promise. “In particular, Medtronic has some preliminary data,” he said, before continuing: “My personal opinion is that the paclitaxel issue will fade over time. I think we have had such a hard time finding a danger signal in any subsequent data. Nevertheless, the whole issue has bought forward the concept of limus-based compounds.”
The “paclitaxel issue” he is referring to here is the increased association with mortality reported by Konstantinos Katsanos (University of Patras, Patras, Greece) et al in December 2018 when paclitaxel devices are used in the lower leg, which caused an international furore about the safety of these devices. Since, multiple analyses have failed to replicate this signal, but, as Schneider pointed out at ISET, the publication opened the door wider for research and development into alternative drugs.
“Here is just one,” Schneider said, showcasing the MED Alliance Selution, a sirolimus-coated balloon from Swiss start-up MedAlliance. “This is their SFA device. It uses micro-reservoirs made out of biodegradeable polymer intermixed with sirolimus for sustained and controlled drug release—typically, the slow and difficult uptake has been the problem with sirolimus.” MedAlliance’s planned clinical programme includes specific trials focusing on BTK disease (SELUTION BTK IDE) and CLTI patients (PRESTIGE, PRESITINE, and STEP).
Concept Medical, another start-up, from India, has recently published a first-in-human series from its XTOSI study, demonstrating good six-month primary patency of its MagicTouch PTA sirolimus-coated balloon in the treatment of BTK arterial lesions, in addition to femoropopliteal lesions. In addition, the US-based Surmodics has a BTK DCB (the Sundance DCB) currently in a first-in-human trial.
“There is also a method of administering limus-based compounds using the Mercator Bullfrog catheter,” Schneider said, which has 510(k) clearance. The Bullfrog device delivers generic dexamethasone to the adventitia, reducing inflammation that can be caused by interventional revascularisation. Delivery is confirmed with the co-administration of contrast.
The final technology Schneider mentioned is the “Eluvia-type technology”, seen in the SAVAL BTK drug-eluting stent system from Boston Scientific, which utilises a polymer as well as paclitaxel, and has been successful in SFA trials. It is now being enrolled in BTK trials. The SAVAL BTK stent system was the first CLTI device to be recognised by the FDA breakthrough device programme.