Lesion Revascularisation Subsequent to Femoropopliteal Spot Stenting Using the Multi-LOC Stent Delivery System

Discussion

Recently, we published results from the multi-centre LOCOMOTIVE Study using the Multi-LOC system in complex FP lesions, and found, the all-cause TLR rate was 9.3% in the overall cohort at 12 months (5). In this single-centre study, we analysed TLR lesions following FP Multi-LOC stenting in a targeted manner.

The study cohort represented a “negative selection” of patients with spot-stented FP lesions. First, according to the LOCOMOTIVE study design, a stent-based strategy was chosen as bailout at the time of the index procedure. Reasons for bailout stenting were i) elastic recoil and/or haemodynamically relevant dissection after pre-dilation of severely calcified stenotic lesions and ii) chronic total occlusions, two of the most challenging subsets of FP disease. With an average of 5.1 Multi-LOC stents implanted per lesion, over half of the index lesion lengths (mean 11.7 cm) had been stented. Three of 10 lesions were chronic total occlusions. Second, the patient cohort analysed in this study underwent TLR due to clinically relevant restenosis. All 10 patients continued smoking and the majority presented hypertension and diabetes mellitus, while two patients stopped taking statins after the index procedure. These factors may have contributed to the occurrence of restenosis.

The main findings of this study confirmed our hypothesis that Multi-LOC stents are not susceptible to fracture or stent-related restenosis but result in significantly more pronounced lumen loss in the inter-stent segments. The stents may be too short (13 mm) to experience relevant biomechanical forces relative to fractures and might not be susceptible to myointimal hyperplasia because of reduced chronic trauma to the vessel wall (short stent length and no oversizing).

While restenosis is a common issue following FP interventions, the mechanisms leading to binary stenosis differ greatly among the different primary revascularisation and scaffolding techniques. Generally, inflammatory reactions of the vessel wall and neointimal proliferation can occur as a result of mechanical dilatation secondary to balloon treatment, either with or without stent deployment (9). Following stenting, foreign body interaction with the vessel wall could lead to stent fatigue and may compromise the integrity of the vessel wall, exacerbating and prolonging the proliferative response, and leading to myointimal hyperplasia and binary stenosis. Regarding restenosis following focal stenting using the Multi-LOC stent device, angiographic follow-up evaluation should be performed to address specific features of this “spot-stenting” technique. While the target lesions were pre-dilated over the entire length (in our TLR cohort with plain-old balloon angioplasty only), stenting should provide vessel scaffolding selectively in lesion segments with high-grade dissections and/or recoil, according to the interventional philosophy to leave as little metal behind as possible. As a result, only the stented segments are subject to chronic outward force of the self-expanding stents and can both increase the in-stent volume during the following months (10) and/or exacerbate the proliferative vessel response, which can lead to in-stent restenosis. Our study allowed the assessment not only of luminal narrowing (negative vascular remodelling resulting from neointimal hyperplasia) but also of a slight luminal enlargement of some of the stented artery segments (positive lumen gain). Both effects seemed to play a minor role in our study cohort. This may be partly due to the fact that stent oversizing was avoided, which is known to promote neointimal proliferation and restenosis (11).

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Figure 3.

Restenosis pattern. Lumen diameter changes assessed by quantitative vascular analysis. The values indicate the loss (positive values) or gain (negative values) of diameter stenosis from the index procedures (final angiograms) to the follow-up angiograms prior to TLR along the target lesion at the predefined measurement sites.

The absence of stent fractures in this study was in accordance with preclinical findings in the porcine model, where short stents did not fracture in actively bended arterial segments compared to longer standard nitinol stents, similar in total length to the multi-stented artery segment (3). Short self-expanding nitinol stents of only 13-mm in length might be too short to experience relevant mechanical stress (e.g. flexion forces). Importantly, stent fracture rates vary between different types of stents. For example, the 12-month fracture rates of 2 cohorts employing the same stent was 3.1% for lesions averaging 7.1 cm in the RESILIENT study (12) compared to 27.1% for lesions averaging 11.8 cm reported in the TIGRIS study BMS arm (13). The mean lesion length of 11.7 cm in our study cohort was similar to the latter study.

Furthermore, using finite element analysis, it has recently been shown that physiological deformation and atherosclerotic plaques, both of which are frequent issues in FP lesions, significantly contribute to early fatigue in stents (14). Numerous efforts have been made to produce “fracture-free” stents able to withstand the rigorous mechanical forces in the FP segment. However, it remains questionable whether improved stent-design could resolve all of the issues associated with foreign body-vessel-interaction. Although the consequences of stent fractures are not fully understood and are inconsistently reported in the literature, the discussion of stent fracture cannot be ignored. In any case, preventing full-metal coverage means minimizing the issues of foreign body-vessel-interactions. In a perfused human cadaver model, none of seven different longer FP stents was able to accommodate all FP deformation modes without either restricting or exacerbating baseline deformations within or outside the stented segment (15). In contrast, the influence of multiple short stents on the inter-stent segments is largely unknown and future characterisation of the biomechanical and haemodynamic consequences of focally stented FP lesions is warranted.

The Tack Endovascular System™ (Intact Vascular, USA), developed to fix dissecting membranes following balloon angioplasty, also aims to provide spot treatment with less metal implantation. The small nitinol rings (6-mm in length) have yielded good results in short (mean length 5.1 cm) and less calcified lesions (graded severe in only 5.4%) in the TOBA II trial, with a TLR rate of 10.5% at 12 months (16). However, due to their lower scaffolding capacity, defined as a lower intended radial force, they may not be suitable for severe vessel responses of recoil and dissections following balloon dilation of severely calcified lesions.

Analogous to preclinical results (3), this study confirms that Multi-LOC stents are not susceptible to in-stent restenosis. In summary, we conclude that the short stents cause little chronic trauma to the vessel wall. Problems mainly arise proximal and distal of the stents. First, in severely calcified lesions, acute flow-limiting dissection or recoil after pre-dilation can barely be mechanically stabilised outside the stents. Both vessel preparation techniques, such as vessel scoring or debulking, as well as prolonged balloon inflation times, have the potential to significantly reduce the rate of dissection (17, 18). While the overall concept of spot stenting has yielded some promising preliminary results, the size of a “spot” and the optimal stent length for an individual lesion are unknown. In some cases, stents longer than 13 mm might be warranted for provisional stenting, still avoiding a “full-metal jacket”. Second, compared to POBA, the benefits of DCB in reducing late lumen loss due to myointimal hyperplasia, binary restenosis, and TLR in FP lesions are well known (19). In our cohort, none of the initial angioplasties had been performed with DCB. In contrast, our follow-up observations after DCB angioplasty showed a long-lasting effect following TLR of spot-stented FP lesions within a three-year period. Even though DCB angioplasty has emerged as the mainstay of therapy for FP lesions (20), many interventionalists perform plain angioplasty without drug release as the standard of therapy for FP lesions, one of the reasons being the limited reimbursement of the higher costs and some recently published safety concerns of Paclitaxel eluting devices.

Finally, the results of the LOCOMOTIVE Extended Study (ClinicalTrials.gov-NCT02900274) should provide further insights concerning the risk factors for TLR following focal stenting of FP lesions.

There are several limitations in our case series. This was an explorative retrospective study of a small and heterogeneous group of symptomatic patients receiving FP TLR. At the time of the index procedure, pre-dilation was performed exclusively using POBA without additional vessel preparation. Furthermore, half of the lesions involved the distal superficial femoral and/or popliteal arteries, which have traditionally been, albeit not in our view, incomprehensively considered as no stent zones. With regards to quantitative analysis, digital subtraction angiography has some shortcomings. As a “luminography” technique, it provides little information about vessel wall morphology and the MLD may be misleading in cases of eccentric stenosis. Due to our efforts to minimise intervention time, radiation, and contrast medium exposure, we avoided different angiographic projection angles. As a consequence, only anterior-posterior projections (0 degree) were available for the quantitative analysis.

Taken together, our data showed that neither stent fractures nor stent-related restenosis seem to play a decisive role in TLR following focal stenting of complex FP lesions with the Multi-LOC stent delivery system. Based on these findings and the follow-up observations after TLR, we hypothesise that focal FP stenting might be even more effective when combined with strategies to optimise plaque development aimed at reducing restenosis in non-stented artery segments, such as i) vessel scoring, ii) debulking, iii) prolonged balloon inflation times, and iv) the use of drug-coated-balloons. Future research can help to further optimize the spot stenting strategy.