Critical Limb-Threatening Ischemia (CLTI)

Coronary artery calcification (CAC) represents a clear sign of advanced atherosclerosis and a strong indicator of coronary artery disease burden and cardiovascular risk. Beyond its established prognostic value, CAC significantly influences plaque biology, lesion morphology, and the technical complexity of percutaneous coronary intervention (PCI). This review summarizes current knowledge on the mechanisms of vascular calcification, its clinical determinants, diagnostic assessment, and therapeutic implications. Vascular calcification is now understood as an active, regulated process involving osteogenic transdifferentiation of vascular smooth muscle cells, inflammatory signaling pathways, extracellular vesicle release, and disturbances in mineral metabolism. Distinct calcification phenotypes exert different effects on plaque stability: micro- and spotty calcifications are frequently linked to plaque vulnerability, whereas dense, sheet-like calcification is more typical of stable fibrocalcific lesions.

The 2026 revision of the Current Procedural Terminology (CPT) codes for lower extremity revascularization introduces important changes that are intended to better align code selection with contemporary endovascular practice.1 In this article, I highlight several key updates and illustrate how I applied the revised codes to a case of chronic limb-threatening ischemia (CLTI) in the setting of multilevel occlusive peripheral artery disease (PAD).

This study underscores the potential of multi-objective optimization in stent design, paving the way for PAD stents that more effectively accommodate femoropopliteal biomechanics and promote favorable mechanical conditions for healing.

Drug-eluting stents are beneficial in treating symptomatic peripheral artery disease (PAD) in the femoropopliteal artery. Data from the ZILVER PTX trial demonstrate that paclitaxel-eluting stents had significantly better 12-month patency rates compared to traditional angioplasty with bare-metal stents for lesions in the femoropopliteal artery (above the knee).

enVVeno Medical has received the investigational device exemption (IDE) approval from the US Food and Drug Administration (FDA) for a pivotal study involving a non-surgical replacement venous valve. The approval allows  enVVeno Medical to begin the Transcatheter Venous Valve Endoprosthesis (TAVVE) pivotal study of its enVVe system for treating severe deep chronic venous insufficiency (CVI).

“The reason for stent graft failure is neointernal hyperplasia that occurs mainly on the edge of the device and sometimes in the middle of the stent graft,” Harduin detailed. The Solaris DE covered stent is built with an impermeable electrospinning PTFE membrane to limit cellular migration, allied with the sirolimus coating to block neointimal hyperplasia and restenosis. “Sirolimus is a safe and effective cytostatic drug that has been used for a long time in interventional cardiology in coronary arteries to prevent neointimal hyperplasia, restenosis, and thrombosis,” said Harduin.
Animal studies of Solaris DE have, to date, shown the persistence of the sirolimus on the outer edge of the device, he said, with one study comparing it to a conventional stent graft finding no instances of neointimal hyperplasia at 60 days following Solaris DE implantation, compared to 4.9mm3 with the conventional device.

The BARISTA trial, led by Lieven Maene (Onze Lieve Vrouw, Aalst, Belgium), enrolled 200 patients with all types of iliac lesions. Significantly, 34% of the study population presented with TASC C and D lesions, representing more complex anatomical scenarios and underscoring the robustness of the clinical evaluation.
At one-year follow-up, the trial demonstrated positive clinical outcomes:

• Freedom from target lesion revascularisation (fTLR): 96.4%
• Freedom from restenosis: 94.1%

LUMIFOLLOW is a multicentre, real-world registry including 542 patients from 15 centres in France. The study reflects routine clinical practice and includes a broad spectrum of lesion complexity. Notably, 43.6% of lesions were classified as TASC C and D, and 24.2% of treated cases were restenotic lesions, underlining the challenging nature of the population evaluated.
At three years, 87.3% of patients remained free from revascularisation, confirming durable treatment effect, states the company. No device-related safety concerns were reported during the follow-up period.

The academic, all-comers SirPAD trial enrolled 1,252 patients with femoropopliteal or below-the-knee PAD who were randomized to receive either the sirolimus-coated balloon MagicTouch PTA or any uncoated balloon angioplasty. The primary outcome of major adverse limb events (MALE), encompassing major unplanned amputations affecting the target limb or target-lesion revascularization for critical ischemia, occurred in 8.8% of patients enrolled in the sirolimus-coated balloon group vs. 15% in the uncoated balloon group at one year, corresponding to a median unbiased estimate of the risk difference of -4.9%. This difference was both noninferior and superior in favour of MagicTouch PTA (Concept Medical Inc.) vs. uncoated balloon. Furthermore, the authors showed a statistically significant reduction in the composite key secondary endpoint of any unplanned target-limb amputation or any target limb revascularization.

Sahil Parikh (Columbia University Irving Medical Center, New York, USA) reported that, at three years, Esprit BTK demonstrated a 33% relative improvement in the composite primary efficacy endpoint of primary patency and limb salvage compared to percutaneous transluminal angioplasty (PTA; 59.5% vs. 44.8%; p=0.0025 log rank test). Parikh added that the Esprit BTK was also associated with significantly lower rates of binary restenosis (38% vs. 49%; p=0.018 log rank test), and lower clinically driven target lesion revascularisation (CD-TLR) rates, though the latter did not reach statistical significance (10.2% vs. 18.4%; p=0.052 log rank test). Furthermore, the presenter shared that safety outcomes, the composite of freedom from major adverse limb events at three years, and perioperative death at 30 days were similar between the two arms (90.8% vs. 94.2%; p=0.23 log rank test).  

“Endovascular thrombectomy has transformed acute ischaemic stroke care, with onset-to-puncture [OTP] time widely recognised as a critical determinant of outcome,” the authors write, outlining the backdrop to their study. “However, emerging evidence suggests that in-hospital procedure time—from arterial puncture to final recanalisation—may have an equally or more significant impact.”

Quantifying rat venous stent patency and endothelialization via histology and microscopy revealed complete patency with anticoagulation and pathological occlusions (RT, ISR) when withholding anticoagulation. This rodent model will facilitate the preclinical testing of future venous stents.

Humans stand alone as the singular species with propensity to develop spontaneous DVT. Because Virchow's original description of a canine model, there has been interest in the development of animal models of thrombosis to mimic the human condition. Initial labors were directed toward development of large mammal models. The transgenic mouse era led toward efforts to translate the existing models into the smaller rodent species. Mice are amenable for the study of venous thrombosis and have the advantages of relatively low cost and the availability of different genetically manipulated strains.

In patients requiring bailout stenting for FPA lesions, adjunctive DCB use was associated with lower 1-year CD-TLR; however, this finding should be considered hypothesis-generating due to the retrospective design and limited sample size. No sustained benefit was observed at 2 years. No signal for increased short-term mortality was identified, although the study was not powered for safety endpoints.

REVA Medical, LLC today announced primary endpoint results from the MOTIV BTK randomized pivotal clinical trial evaluating the MOTIV® sirolimus-eluting bioresorbable vascular scaffold in patients with critical limb-threatening ischemia (CLTI). The results were presented today at the Charing Cross International Symposium in London, UK. Motive Sirolimus- Eluting Bioresorbable Vascular Scaffold System. The MOTIV BTK trial met both its primary safety and efficacy endpoints, demonstrating that the MOTIV scaffold provides a statistically significant improvement in clinical outcomes compared to the current standard of care, balloon angioplasty.

In patients with chronic limb-threatening ischemia (CLTI) who have run out of treatment options, a blood flow-diverting procedure in the foot improves several measures of quality of life (QoL) in addition to lowering the risk of major amputation, according to a secondary analysis of the PROMISE III trial.
At 6 months, patients reported being less bothered about poor circulation in their legs compared with before the procedure, as well as more participation in social activities, better sleeping habits, and fewer daily burdens associated with having open wounds.

The FDA’s letter indicates that, upon completing its review, it determined that it is unable to approve the PMA for VenoValve in its current form. According to a news release, the FDA indicated that the favorable revised Venous Clinical Severity Score (rVCSS) data generated by the study to show clinical improvement, together with the improvements in pain scores and venous-specific quality of life indicators, were not sufficient on their own to determine the favorability of the risk-benefit profile for VenoValve.
EnVVeno Medical said that, without a specific hemodynamic measurement that correlates with patient improvement, the FDA raised concerns about bias. The agency also considered the possibility that clinical improvement occurred as a result of the patients being enrolled in a study.
Additionally, the company said the FDA focused on safety concerns attributed to the associated open surgical procedure. That required rehospitalizations, the company said. However, it would not expect to see similar safety events with a non-surgical replacement valve.

The RFS device is a bioresorbable stent built from microfibres, providing structural support to instantly open, and facilitate the reconstruction of the artery. Due to the porous design of the implant, patients’ own cells infiltrate into the mesh, triggering the formation of new vascular tissue. While the artery is being reconstructed from the inside-out, the synthetic implant gradually resorbs and ultimately disappears over time.
At LINC, Brodmann expanded on some key characteristics of the RFS. “The device is a fully electrospun tubular conduit with fibrous micro-architecture and a strutless design,” the presenter noted, also highlighting the implant’s suitability for transcatheter delivery due to a balloon-expandable design.

Launched in Europe in 2016 and the USA two years later following successful results from the IMPERIAL randomised controlled trial (RCT),1 the Eluvia DES is designed to provide sustained drug release and efficient drug transfer with the aim of overcoming the challenge of restenosis in the superficial femoral artery (SFA).
Steiner’s clinical experience with the Eluvia DES dates back several years. At this time, she and colleagues conducted the BEST-SFA RCT, in which Eluvia was used as a comparator. “What we observed in this analysis, and in our own clinical experience, was that the stent performed very well, effectively inhibiting the need for reintervention.” Steiner recalls. Two-year results of this study were published in 2024 in JACC: Cardiovascular Interventions.2

12 Month Outcomes of the SUCCESS PTA Study show consistent safety and effectiveness in claudicant and CLTI patients when using the SELUTION SLR™ drug eluting balloon.

Drug-coated balloons and stents don’t reduce the risk of amputation or improve quality of life for people with peripheral artery disease in the legs. That’s the takeaway from two major clinical trials led by researchers at the University of Gothenburg.