Discussion
The main findings of this study are as follows: (1) the neointima increase was significantly larger in the main branches of both examined stents as assessed in QCA (late lumen loss) as well as in IVUS (neointima burden), (2) the middle part of the stent was not associated with the excessive neointima proliferation, (3) the neointima increase was significantly smaller in BiOSS® LIM stents than in BiOSS® Expert stents, and 94) optimization techniques in case of BiOSS® LIM stents greatly improved the angiographic and IVUS outcomes.
On the market there are two versions of the BiOSS® stent: the BiOSS® Expert eluting paclitaxel and BiOSS® LIM eluting sirolimus. In our study both stents were assessed. These two populations did not differ significantly regarding baseline characteristics of patients nor lesions. But consequently the BiOSS® LIM stent proved to be superior comparing with the BiOSS® Expert stent taking into consideration both angiographic as well as IVUS parameters. The mean LLL was significantly lower in the BiOSS® LIM group than in the BIOSS® Expert group, 0.32 ± 0.11 mm vs 0.39 ± 0.14 mm (P < 0.05), respectively. Similarly, the neointima burden was larger in the BiOSS® Expert group, 24.7 ± 7.5 % vs 19.4 ± 8.6 % (P < 0.05), respectively.
The analysis of clinical outcomes in the studied population seems to confirm their association with the neointimal proliferation. Although, probably due to the small number of patients there was only a trend in favor of the BiOSS® LIM stent [TLR 3/11 (27.2 %) vs 2/23 (8.7 %), P = 0.15], but in the whole registry population of the BiOSS Expert® stent the 12-month TLR rate was 11.3 % (7/63), whereas in the BiOSS LIM® registry it reached 8.3 % (5/60), P = 005 [
6,
7].
The obtained results are concert with those in previous papers showing that sirolimus-eluting stents (SES) are better than paclitaxel-eluting ones (PES) in terms of efficacy in the bifurcation treatment [
12]. In paper Chen et al. after 12-month follow-up results in paclitaxel group differed significantly with sirolimus group regarding to the rate of TLR, TVR and MACE, 12.2 % vs 3.2 % (P = 0.006), 14.4 % vs 4.9 % (P = 0.02) and 20 % vs 10.3 % (P = 0.04), respectively [
13]. However, on contrary to us, no control angiography was planned after 12 months. Moreover, Song et al. published paper comparing PES and SES in bifurcation stenting [
14]. After 2 years of follow-up in PES group the rate of MACE was 28.6 % and in SES 10.6 % (P = 0.03), whereas the LLL was 1.03 ± 0.45 and 0.28 ± 0.54 mm (P < 0.001) respectively. Also, in a meta-analysis it was proved that when comparing with PES, SES reduced the incidence of TLR, main-branch restenosis and MACE in coronary bifurcation intervention, while the risk of stent thrombosis was similar between SES and PES groups [
15].
In our previous paper, the successful BiOSS® Expert stent implantation caused significant increase in LA in each part of the bifurcation: the main vessel, the bifurcation site as well as in the main branch. Actually, the only significant difference between conventional drug-eluting stents vs BiOSS® stents after intervention was found for the window length, which was significantly longer in the group where the BiOSS® stent was implanted (P = 0.01) [
9].
After 12 months, the window length was comparable as just after stenting. In the follow-up the window length in the BiOSS® Expert group was 2.18 ± 0.27 mm (value just after stenting 2.21 ± 0.37 mm, P = NS). The neointima proliferation was larger in the main branch comparing with the main vessel. This was true both for the BiOSS® Expert and for the BiOSS® LIM stents. The Fig.
2a shows LLL (main vessel 0.36 ± 0.14 vs 0.29 ± 0.11, main branch 0.41 ± 0.15 vs 0.35 ± 0.12 mm). Moreover, in the Fig.
3 there is presented neointima burden in three parts of the stent. Similarly, in the BiOSS Expert® group there is higher neointima proliferation in the main vessel (22.8 ± 5.6 % vs 16.9 ± 6.1 %, P < 0.05) and in the main branch (36.1 ± 6.5 % vs 27.6 ± 8.7 %, P < 0.05) than in the BiOSS® LIM group. There was no difference between stents at the bifurcation site where there are only two stent struts (15.1 ± 3.8 % vs 13.6 ± 5.4 %, P = NS). Worth mentioning is the fact that this area (bifurcation site) is the region with the smallest neointima burden in the whole stent. Also, in IVUS examination the location of minimal LA site was quite remote from the bifurcation site. Interestingly, there were fewer struts in SB inflow with BiOSS LIM, probably due to higher performance of FKB/POT in this group compared to BiOSS Expert.
The larger neointima proliferation in the main branch might be explained by the smaller diameter of this part of the vessel. And it was proven that in stents with smaller diameter there is a higher risk of neointima proliferation and cardiovascular events [
16]. However, we were searching for a much more precise explanation. Measurements of vessel, lumen and plaque areas before and after stenting created an opportunity to identify mechanisms of the lumen enlargement at regions of interest including vessel extension (stretch) and plaque re-distribution. This first mechanism (more stimulating neointimal proliferation) overweighted in distal limb (means distal branch) while in proximal limb (main vessel) and in the mid zone (carina region) this mechanism was less pronounced (43 % vs 46 %, respectively main branch and mid zone) [
9]. This less traumatic mechanism of lumen enlargement somehow is responsible for relatively small neointimal proliferation at these levels, however one must remember that additional optimization (FKB/POT) was not performed in that population. Nevertheless, it is pretty sure that vessel expansion would not reach an excessive degree, especially with a dedicated bifurcation device such as BiOSS, which is built on a metallic platform with different diameters at proximal (larger) and distal (smaller) parts in order to optimize scaffold and expansion at the bifurcation anatomy, while maintaining side branch patency.
Additionally, two more factors have the influence on the intima proliferation: proper stent size selection and correct stent strut apposition. In our study in the IVUS analysis the proximal and distal parts of the BiOSS® stents were well apposed. But the distal part of the stent was not optimized during the implantation procedure. FKB/POT optimized the proximal part of the stent only. Additional analysis of the mean ratio of stent area to vessel area calculated for main vessels and main branches in both groups allowed us to assess stent expansion. Obtained results showed that sizing was more proper in case of the main vessel and proved the crucial role of FKB/POT for better outcomes (Fig.
3b, c). Still, one would consider that the amount of plaque along with its distribution within the bifurcation segments (higher amount in the MB) at baseline could explain these findings, at least to certain extent; however, this hypothesis remains purely speculative, as IVUS was not systematically performed at baseline.
FKB inflation technique as well as proxi POT mal optimization technique are the two most commonly recommended by the European Bifurcation Club [
17]. Since there were no POT cases in the BiOSS® Expert implantations, we analyzed the influence of these two techniques only in the BiOSS® LIM group. Indeed, we found that in the BiOSS® LIM the neointima proliferation in the main vessel and at the bifurcation site was significantly lower in the group were FKB/POT was applied (Fig.
2b; Table
5). There was no difference in the neointima proliferation in the main branch between these two groups. It seems that optimization techniques are crucial for good results of the BiOSS® stent implantation and ensure the low neointima proliferation.
These results are in agreement with our previous clinical trial, POLBOS I, in which application of FKB and POT was associated with lower LLL and better clinical outcomes [
4]. These findings were confirmed in other studies, also in trials with other dedicated bifurcation stents [
18‐
20].
Study limitations
This study has also some limitations. The number of treated patients that underwent IVUS examination at late follow-up was small and they were selected by operators based on operator’s skills and the imaging catheter availability. Bifurcation lesions a priori qualified to the treatment with a two-stent technique were excluded. Also, no uniform implant technique was used, however procedures were performed by operators highly experienced in BiOSS® stent implantation. And additionally, no control group was introduced to compare the use of this dedicated bifurcation stent and stenting with other devices and techniques.