Introduction
Balloon angioplasty and stent implantation are popular in patients with peripheral artery disease (PAD) [
1‐
3]. The self-expanding nitinol stent (SENS) for superficial femoral artery (SFA) lesions is morphologically and clinically superior to balloon angioplasty [
2,
4,
5]. However, stent size influences clinical outcomes [
6,
7]. Implanted SENS is commonly oversized in the SFA, especially at the distal portion due to tapered diameter of SFA for long SENS [
8‐
10]. SFA stents are under dynamic stress to external forces including bending, twisting, torsion, elongation, foreshortening and external compression [
11,
12]. The mechanical stresses to the SFA are associated with an increased risk of stent fracture and subsequent significant restenosis [
11,
13]. The chronic outward force (COF) exerted by a SENS is another important factor to cause restenosis, and several investigations evaluated the effect of SENS oversizing on the risk of in-stent restenosis (ISR) [
6,
14‐
16]. COF could produce continuous mechanical stimulation of the arterial wall, which can increase neointimal hyperplasia and lead to significant ISR [
17].
This study aimed to evaluate the impact of SENS oversizing on ISR of SFA. We examined clinical and animal experiments data to determine the impact of COF on the arterial wall, and investigated the impact of SENS oversizing with respect to continued expansion following stenting and the mid-term histological impact of oversized stent on SFA.
Discussion
The major findings of the impact of COF on arterial responses of SFA stent are summarized as follows. First, clinical study showed that for long SFA stent, the stent-to-artery ratio was significantly higher in the distal stent than in the proximal stent. The incidence of ISR and mean percentage of restenosis was significantly higher at the distal site, particularly in the implanted stent longer than 100 mm. Second, in animal models, the incidence of ISR was higher, lumen area was smaller, and neointimal and stenosis area were larger and there was a trend toward higher inflammation score in the oversized group. Third, the stent to artery ratio was 1.51 times of the standard for diagnosing stenosis using ROC analysis. These results support the idea that stent oversizing significantly increases the intramural stress to stimulate smooth muscle in the vessel, leading to inflammatory response and pathologic stress in the artery wall that cause irreversible damage [
19].
Several clinical trials demonstrated the benefit of SENS implantation over angioplasty for stenosis or occlusion of the SFA [
2,
4,
20]. However, SFA poses unique challenge for endovascular stenting. SFA is a long muscular artery that is fixed between the hip and the knee. Complex motions of the hip joint can impose complex external mechanical stresses on the SFA, including flexion, compression and torsion [
11]. SFA is further exposed to longitudinal and lateral compressional stress as the artery dives through the Hunter canal between the muscle bodies of the anterior and medial compartments of the thigh [
12]. Currently, a stent diameter of 1–2 mm oversizing is recommended in SFA stent implantation [
8,
21]. For a self-expanding non-tapered nitinol stent, it will be implanted in accordance with the proximal diameter of the reference vessel, since the stent is self-tapered at the distal site after stenting. Therefore, the distal portion of the long SENS will exert stronger COF to distal SFA, leading to higher incidence of intimal hyperplasia and subsequent restenosis.
Previous studies reported that average reference vessel diameter of SFA is 5 mm, and most commercially available stent has a diameter of 7 mm [
8‐
10,
22,
23]. However, SFA consists of tapered vessels. Therefore, in this procedure, a larger diameter stent will be implanted into the smaller SFA distal portion. The different diameters of the proximal and distal portions of stent impose a wall stress on the arterial wall. Vessel wall injury is an important factor during stent implantation [
15]. The main reason for restenosis is adverse remodeling caused by endothelial injury, inflammation of atherosclerosis plaque, hemodynamic factors, and mechanical stress from a permanent stent [
24].
The incidence of ISR depends on the type, design and length of the implanted stent. Innovative stent design may decrease ISR and improve clinical outcomes. The unique design of the Supera Peripheral Stent (Abbott Vascular, Abbott Park, IL) aimed to overcome issues related to areas of high flexion and minimal COF [
9]. Recently, the Supera Interwoven Nitinol Stent Outcomes in the Above-Knee Interventions (SAKE) study showed high rate of patency at 6 and 12 months with no stent restenosis for femoropopliteal disease treated with novel interwoven-wire Supera stent [
25]. Furthermore, the outcomes after popliteal stenting with the Supera stent from the Leipzing Supera popliteal artery registry showed 6- and 12-month primary patency rate of 94.6% and 87.7%, respectively, with 4 patients experiencing in-stent occlusions and 6 patients experiencing in-stent restenosis [
26]. Optimizing stent design can improve stent performance [
27].
The length of the SENS is also an important factor of ISR. Long stenosis (> 100 mm) had poor outcome, with restenosis rate exceeding 70% at 1 year [
28]. The restenosis rates vary between 35 and 65% at 6–12 months for lesions > 100 cm [
29]. In our study, the restenosis rate was significantly higher in the distal portion than in the proximal portion of the long stent (> 100 mm). Conversely, there was no difference in short lesions (< 100 mm). These results revealed the importance of COF caused by oversized SENS in the distal SFA.
Stents are designed to be larger in diameter than the healthy artery, which is referred as “stent oversizing” [
19]. The significant diameter change usually occurs in carotid artery stenting, but also occurs in femoral arteries [
19]. The mechanical environment of peripheral arteries could be the predominant cause of relatively higher restenosis rate [
13]. Although the ideal oversizing ratio is stent specific, nitinol stent oversizing has a very small impact on the immediate lumen gain [
30]. However, severe oversizing (stent-to-artery ratio > 1.4:1) resulted in profound long-term histological changes including exuberant neointimal proliferation and luminal stenosis in animal models [
6]. These results suggest that the oversizing ratio is an important factor for neointimal formation in SENS, and self-expanding stents without exceeding an oversizing ratio of 1.4 is crucial for long-term patency in peripheral artery stenting [
16]. Furthermore, when a non-tapered stent is placed in vessels with a large discrepancy in diameter, attention must be paid for increased neointimal hyperplasia in the oversized side [
17]. In our porcine model, the cutoff ratio of SENS to artery ratio was calculated to be 1.51. The restenosis rate was significantly higher in oversized group than in control group.
In summary, we investigated the impact of oversized SENS implanted in tapered SFA arteries on restenosis caused by COF. Oversizing of the stent is an important determinant of final arterial wall diameter and stress. Therefore, SENS with optimal oversizing should be designed in cases with significant arterial tapering.
Study limitations
In clinical study, our single-center retrospective study design only allowed for analysis based on our routine clinical practice. The sample size did not provide sufficient power to detect ISR incidence or compare clinical events. Operators were not blinded to baseline measures. Finally, our data reflected in-hospital outcomes, and we did not analyze long-term outcomes. Therefore, future randomized studies are needed to confirm our conclusions.
In animal study, the sample size of 22 stents was small, and we did not find significant differences in incidence of restenosis or related parameters between the two groups. In addition, we used healthy animals with non-atherosclerotic arteries. Although blood vessels of pig are very similar to those of human, the results of animal experiments may not be same as those of clinical studies.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.