Author + information
- Received January 19, 2016
- Revision received March 15, 2016
- Accepted April 7, 2016
- Published online July 11, 2016.
- François Derimay, MD, MSca,
- Géraud Souteyrand, MD, MScb,
- Pascal Motreff, MD, PhDb,
- Patrice Guerin, MD, PhDc,
- Paul Pilet, B Engc,
- Jacques Ohayon, PhDd,
- Olivier Darremont, MDe,
- Gilles Rioufol, MD, PhDa and
- Gérard Finet, MD, PhDa,∗ ()
- aDepartment of Interventional Cardiology, Cardiovascular Hospital and Claude Bernard University and INSERM Unit 1060 CARMEN, Lyon, France
- bCardiology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France
- cCardiology, UMR 915, Institut du Thorax, Nantes, France
- dLaboratory TIMC-IMAG, DynaCell, CNRS UMR 5525, Institut de l’Ingénierie et de l’Information de Santé, Grenoble, France
- eClinique Saint Augustin, Bordeaux, France
- ↵∗Reprint requests and correspondence:
Prof. Gérard Finet, Département de Cardiologie, Hôpital Cardiologique L. Pradel, B.P Lyon-Montchat, 69394 Lyon Cedex 03, France.
Objectives The aim of this fractal bifurcation bench study was to compare provisional bifurcation stenting with a “re-POT” sequence, comprising a proximal optimizing technique (POT), side branch inflation, and final POT, between a bioresorbable vascular scaffold (BVS) and a metallic stent.
Background Re-POT proved significantly better than kissing balloon inflation in maintaining circular geometry without overstretch in metal stents, while significantly reducing side branch ostium strut obstruction and global strut malapposition. This should be useful for BVSs, which are more easily breakable.
Methods Twenty left main–like and 20 left anterior descending–like fractal coronary bifurcation bench models used 10 each 2.5 × 24 mm and 3.5 × 24 mm Absorb (Ab) BVSs and 10 each 2.5 × 24 mm and 3.5 × 24 mm XIENCE Xpedition (XX) metal stents, implanted by re-POT, with optical coherence tomographic analysis at each step and micro–computed tomographic analysis of Ab devices to detect strut fracture.
Results With Ab devices, re-POT reduced percentage strut malapposition close to XX rates (0.8 ± 0.7% vs. 0.0 ± 0.0%, p < 0.05; 3.5 ± 1.7% vs. 0.3 ± 0.6%, p < 0.05), conserving proximal circularity (elliptical ratio, 1.04 vs. 1.03 and 1.04 vs. 1.04; p = NS). Mean post-re-POT proximal expansion was 0.6 ± 0.1 mm (+21.6 ± 2.1%) for 2.5-mm and 1.0 ± 0.1 mm (+23.6 ± 2.2%) for 3.5-mm Ab devices, with only 1 strut fracture (left anterior descending–like bench). Side branch ostium strut obstruction was greater with Ab scaffolds than XX stents: 41.1 ± 9.4% versus 16.4 ± 8.1% (p < 0.05) and 31.8 ± 3.2% versus 10.0 ± 5.3% (p < 0.05), respectively, for 2.5- and 3.5-mm scaffolds and stents. Ab scaffolds showed 2 ± 1% moderate but significant late recoil as of 1 h, reaching 4 ± 2% by 24 h (p < 0.05).
Conclusions Re-POT optimized most Ab provisional bifurcation treatments, without fracture, respecting fractal geometry, and without exceeding 1.0-mm proximal differential diameter.
Clinical interest in bioresorbable vascular scaffolds (BVSs) has been consistently confirmed and validated in successive randomized studies (1–4), with about 23% of cases involving treatment of bifurcation lesions (5).
Optimal coronary bifurcation treatment requires controlled deformation of the 3-dimensional meshwork of the scaffold or stent, to respect both the fractal geometry of coronary bifurcations (6) and, more precisely, the expected differential diameter between mother vessel (MoV) and main branch (MB) (7), and as far as possible to free the side branch (SB) ostium of struts while minimizing strut malapposition.
However, the mechanical properties of polymeric scaffolds are such that the increase in tensile strength of the semicrystalline polymer needed to achieve sufficient rigidity after deployment lowers the fracture threshold (8). Thus, expansion is limited by an increased risk for strut fracture. Optimization by kissing balloon inflation (KBI) is thus ruled out mechanically. According to fractal geometry, juxtaposing 2 balloons in the MoV with the diameters of the 2 daughter vessels fails to match the fractal law, inducing theoretical MoV overexpansion of 47%, as confirmed in bifurcation bench models (9,10).
A very informative recent study by Foin et al. (11) showed that BVSs can be focally overexpanded by a maximum of 1.0 mm over the nominal diameter without crossing the fracture threshold. In agreement with fractal geometry, 76% of epicardial coronary bifurcations show an expected differential diameter of <1.0 mm between MoV and MB (7). Moreover, Ormiston et al. (12,13) confirmed that a 3.0-mm Absorb (Ab) BVS strut cell (Abbott Vascular, Santa Clara, California) could be dilated to 3.0 mm at 10/12 atm without damage, that the proximal optimizing technique (POT) caused no fractures with overexpansion up to 3.8 mm diameter at 20 atm in a 3.0-mm scaffold (ΔD = 0.8 mm), and that in practice the range of use of mini-KBI was more complex and uncertain.
Recently, a novel sequence without KBI, called “re-POT,” comprising an initial POT, SB inflation, and final POT, significantly optimized the final result of provisional coronary bifurcation stenting using metallic stents, in comparison with 5 other techniques, maintaining circular geometry while significantly reducing SB ostium strut obstruction and global strut malapposition (10).
In the present experimental study, we used optical coherence tomographic (OCT) imaging and microfocus x-ray computed tomography on 2 types of fractal coronary bifurcation bench model using the polymeric Ab BVS and the metallic XIENCE Xpedition (XX) stent (Abbott Vascular) to compare and quantify the re-POT sequence in provisional stenting.
Ten drug-eluting scaffolds or last-generation stents (polymeric Ab BVS and metallic XX stent) were implanted in 2 different types of fractal coronary bifurcation bench, using the re-POT sequence, for a total of 40 implantations, following the flowchart shown in Figure 1. In all 4 groups, implant diameter took the MB as a reference, as recommended by the European Bifurcation Club for metal stents (14).
Fractal coronary bifurcation bench models
Two different fractal coronary bifurcation bench models were designed: 1) one approximating the dimensions of a left anterior descending coronary artery (LAD) bifurcation (“LAD-like” bifurcation bench model: MoV, MB, and SB diameters, 3.05, 2.5, and 2.0 mm; MB/SB bifurcation angle, 70°); and 2) the other approximating a left main coronary artery (LM) bifurcation (“LM-like” bifurcation bench model: MoV, MB, and SB diameters, 4.55, 3.5, and 3.2 mm; MB/SB bifurcation angle, 80°), both respecting fractal geometry (6). The 1-mm-thick polyvinyl chloride models were manufactured to order (Segula Technologies, Saint-Priest, France). Elasticity was required to approximate that of a fibroatheromatous arterial wall (i.e., 700 to 1,500 kPa), assessed on uniaxial extension test (TA-XT2i texture analyzer; Stable Micro Systems, Surrey, United Kingdom) to determine the true Young’s modulus after the polymerization process. Geometry was systematically quantified on OCT ahead of implantation, as polymerization and unmolding release the residual stress acquired during the manufacturing process, inducing recoil.
Experimentation was performed in a bath held at 37°C, in which the bench models were fixed on a support to maintain angles constant throughout the various steps of the procedure. BVS models were kept in the bath for a further 24 h after implantation to study possible late recoil.
Two types of stent were used. The Ab everolimus-eluting BVS is composed of poly-l-lactic acid polymer covered by poly-dl-lactic acid eluting everolimus. Strut thickness was 157 mm. The Ab device comprises 20 rings in the 3.5 × 23 mm model (0.87 ring/mm length) and 24 in the 2.5 × 23 mm model (1.04 ring/mm length). Rings are connected by 3 “peak-to-valley” connectors with 60° offset between rings. The rings are 190 μm wide in the 2.5-mm model and 216 μm wide in the 3.5-mm model, the width of the connectors being 140 μm in both. Sinusoid height is 0.94 mm in the 2.5- and 3.0-mm models and 1.125 mm in the 3.5-mm model.
The XX metallic drug-eluting stent is in cobalt-chromium, with 81-mm strut thickness, plus 8-mm nonresorbable everolimus coating. The same sizes were used as for the Ab BVS: 3.5 × 23 and 2.5 × 23 mm.
In the re-POT sequence (initial POT, SB inflation, and final POT), described in detail by Finet et al. (10), following stent implantation at the reference MB diameter,
1. An initial POT is performed using a Maverick compliant balloon (Boston Scientific Corporation, Marlborough, Massachusetts) to achieve radial expansion of the scaffold or stent adapted to the MoV reference diameter, to obtain a stent/artery ratio >1.0 (4.0 × 15 mm for the LM-like bench model and 3.0 × 15 mm for the LAD-like bench model). Optimal inflation pressures were determined from compliance charts provided by the manufacturer, and effects were checked on OCT imaging: 10 and 14 atm for the Ab 2.5- and 3.5-mm scaffolds, respectively, and 12 and 18 atm for the XX 2.5- and 3.5-mm stents, respectively. The POT balloon was positioned precisely, with the medial edge of the distal radiopaque marker lying in the cross-sectional plane of the carina.
2. The SB ostium strut cells were then opened using a Maverick compliant balloon of 3.0 × 15 mm for the LM-like and 2.0 × 15 mm for the LAD-like bench model. SB inflation pressures were 8 atm for Ab and 14 atm for XX.
3. Last, a final POT was performed with the same criteria as for the initial POT.
Following the manufacturer’s guidelines, each inflation in the BVSs was performed stepwise with 5-s 2-atm increments up to optimal pressure, which was then maintained for 30 s.
Two-dimensional and three-dimensional OCT acquisition and analysis
Two-dimensional and 3-dimensional OCT acquisition used the Lunawave optical frequency domain imaging system (Terumo Europe, Leuven, Belgium) and the dedicated FastView optical frequency domain imaging catheter. Automatic pull-back speed was 10 mm/s after each sequence. Two-dimensional OCT images were quantitatively analyzed retrospectively using the Terumo software. MoV and MB parameters for all bench models and scaffold and stent platforms comprised mean diameter, maximal diameter, and minimal diameter. Ellipticity ratio was calculated as maximal diameter/minimal diameter, with 1.0 corresponding to perfect circularity. Strut malapposition on OCT imaging was defined by the sum of stent diameter, coating thickness, and 15-μm OCT axial resolution (i.e., 175 μm for Ab and 105 μm for XX). Overall malapposition was quantified on each slice as percentage malapposed struts in the total number of struts analyzed. OCT slices were acquired millimeter by millimeter along the entire stent. To assess possible late Ab recoil, as suggested by Ormiston et al. (12), supplementary 2-dimensional OCT acquisitions were performed 1 and 24 h after the re-POT sequence. To assess the recoil component imputable to Ab or to the bench model, a mean diameter ratio was calculated between the Ab and bench model diameters at 1 and 24 h on one hand and the reference diameters immediately after re-POT on the other.
A 3-dimensional OCT carpet view of the stent was reconstructed at each step, using the Terumo software. Acquisition was oriented to optimize SB ostium visualization. SB obstruction (SBO) was calculated as (A1/A2) × 100%, where A1 is the total area of struts facing the ostium, and A2 is the area of the ostium; A1 and A2 were measured manually on digital planimetry.
Microfocus x-ray computerized tomography
The bench models were kept in a water bath. Ab (n = 20) and XX (n = 20) models were scanned (SkyScan 1272; Bruker, Brussels, Belgium) at a resolution of 10 μm/pixel. Fracture was defined by loss of continuity in the scaffold or stent, quantified by 2 independent observers on 3-dimensional reconstruction to determine location (MoV, bifurcation, or MB) and type (connector or ring). In all, 690 connectors and 240 rings were analyzed in 2.5-mm Ab scaffolds and 570 connectors and 200 rings in 3.5-mm Ab scaffolds.
The quantitative variables indicate changes in bifurcation bench model geometry during the various scaffold and stenting optimization phases during the re-POT sequence and are presented as mean ± SD. The Mann-Whitney nonparametric unmatched test for continuous quantitative variables was used to compare re-POT strategy between Ab and XX devices. The Wilcoxon nonparametric matched-pairs test was used to compare the various steps in the re-POT sequence in Ab implantation. Analysis used SPSS version 16.0 software (SPSS, Inc., Chicago, Illinois). A p value < .05 was considered to indicate statistical significance.
Bifurcation model fractal geometry
After polymerization and unmolding, bench models are subject to retraction, which reduces the luminal diameter specified in the design. Real measurements were therefore made for each model and are shown in Table 1. Retraction tended to be homogeneous, and the linear fractal ratio was conserved, at a mean value of 0.69 instead of the theoretical value of 0.678. Balloon inflation in the various steps of the re-POT sequence took account of these real values.
Final comparative analysis of the re-POT strategy between the Ab and the XX
All 20 Ab and 20 XX devices were successfully implanted with the re-POT sequence, without complications (Online Videos 1, 2, 3, and 4). Table 1 compares results between Ab and XX for the 2 types of bifurcation bench model.
Step-by-step analysis of the re-POT sequence in Ab scaffolds
Figures 2 and 3 present a quantitative comparison of effects in each step of the re-POT sequence using the 2.5-mm Ab in the LAD-like bench model and the 3.5-mm Ab in the LM-like model. A single BVS fracture was seen on microfocus x-ray computed tomography, in a ring facing the SB ostium in a 2.5-mm Ab (i.e., 1 site [ring or connector] out of 1,700) (Figure 4). The fracture was not visible on 2-dimensional or 3-dimensional OCT (Online Video 5).
Analysis of late recoil
Ab scaffolds showed 2 ± 1% moderate but significant late recoil as of 1 h, reaching 4 ± 2% by 24 h (p < 0.05), regardless of bench model (Figure 5). Absolute elastic recoil appeared to be constant and moderate regardless of initial scaffold diameter: 0.12 ± 0.05 and 0.12 ± 0.06 mm, respectively, for 2.5- and 3.5-mm Ab scaffolds.
In this experimental study performed on 40 fractal bifurcation bench models, we compared the effects of the re-POT sequence for provisional stenting between the Ab BVS and the XX metal stent. With the Ab, the re-POT sequence: 1) restructured the proximal segment of the scaffold so as to respect bifurcation fractal geometry (mean difference between MoV and MB 0.6 ± 0.1 mm and 1.0 ± 0.1 mm for Ab 2.5 and 3.5 mm, respectively), with only 1 strut fracture site out of the 1,700 sites possible, or 1 fracture for a total of 440 rings and none in a total of 1,260 connectors; 2) maintained scaffold integrity and circular proximal bifurcation segment geometry, with an ellipticity ratio of 1.04 ± 0.02, identical to that found with the XX metal stent; 3) minimized overall percentage strut malapposition, although with a significant difference (p < 0.05) from the rate obtained with the XX metal stent (respectively, 0.8 ± 0.8% vs. 0.0 ± 0.0% for the 2.5-mm model and 3.5 ± 1.7% vs. 0.3 ± 0.6% for the 3.5-mm model); and 4) left a higher percentage (p < 0.05) of final SB strut obstruction than the XX stent (41.1 ± 9.4% vs. 16.4 ± 8.1% for the 2.5-mm model and 31.8 ± 3.2% vs. 10.0 ± 5.3% for the 3.5-mm model).
Confirmation of the benefit of initial POT with the Ab BVS
Analysis of the behavior of the Ab BVS at each stage of the re-POT sequence confirmed the absolute necessity of the initial POT step (Figures 2 and 3). In itself it corrected most malappositions (p < 0.05), with rates falling from 7.4 ± 8.4% to 1.1 ± 1.1% for the 2.5-mm model and from 64.2 ± 3.8% to 5.0 ± 2.8% for the 3.5-mm model. Moreover, as with metallic drug-eluting stents (10), initial POT with the Ab reduced SBO (p < 0.05) from 54.9 ± 9.5% to 47.2 ± 6.0% and from 45.8 ± 5.2% to 37.1 ± 3.4% for the 2.5- and 3.5-mm models, respectively. Furthermore, these benefits were obtained without scaffold fracture.
Step-by-step benefit of the full re-POT sequence with the Ab BVS
Functionally, SB opening seems required when SB diameter exceeds 2.0 mm (15), and full re-POT provides the optimal mechanical compromise in provisional stenting with the Ab. Final strut malapposition and SBO were significantly reduced. Although the final POT led to greater SBO than with isolated SB inflation (from 38.8 ± 9.1% to 41.1 ± 9.4% [p < 0.05] and from 23.6 ± 6.4% to 31.8 ± 3.2% [p < 0.05] with the 2.5- and 3.5-mm Ab models, respectively), these rates were lower than with isolated POT (p < 0.05). Moreover, final POT reduced malapposition following SB inflation, from 1.8 ± 1.0% to 0.8 ± 0.8% (p < 0.05) and from 7.2 ± 4.3% to 3.5 ± 1.7% (p < 0.05) with the 2.5- and 3.5-mm models, respectively. The significant difference in SBO between the Ab and XX was due to the wider struts of the Ab compared with the XX (190 and 216 μm vs. 81 μm), the larger cover area (27% vs. 13%, respectively), and, probably, greater elastic recoil, leading to significantly different results between the 2.0-mm ostium of the LAD-like and 3.0-mm ostium of the LM-like bench model (41.1 ± 9.4% vs. 31.8 ± 3.2%, p < 0.05) (late recoil also appearing in Figure 5). These differences were due at least partly to initial relative underinflation of the Ab (8 atm) compared with the XX (14 atm), following the manufacturer’s instructions, leading to relatively greater immediate recoil with the Ab (p < 0.05), expressed in a lower stent-to-artery ratio: 1.09 ± 0.03 vs. 1.15 ± 0.03 for the LAD-like and 1.04 ± 0.02 vs. 1.07 ± 0.02 for the LM-like bench model. Reduced SBO should be a systematic objective, to prevent tissue bridges, acting as “membranes” of neointimal tissue stretching between malapposed struts (16).
Strut fracture and re-POT sequence with the Ab BVS
The Ab polymeric scaffold is liable to fracture, with significantly lower elongation at breakage than in metallic stents, especially during KBI (17) or mini-KBI (13). In the present study, there was only 1 isolated case of fracture, without mechanical impact on the stent, in a ring facing the SB ostium in a 2.5-mm Ab. This fracture was probably induced by SB inflation. Performing POT with the Ab did not cause any fractures and increased mean diameter by 0.6 ± 0.1 mm (21.6 ± 2.1%) (p < 0.05) with the 2.5-mm Ab and 1.0 ± 0.1 mm (23.6 ± 2.2%) (p < 0.05) with the 3.5-mm Ab. These findings agree with those of a recent study by Foin et al. (11), who found a fracture threshold of 1.0 mm after proximal dilation with the 3.5-mm Ab. As the Ab range does not include diameters >3.5 mm, the Ab can be used only in bifurcations in which MB diameter does not exceed 3.5 mm with a differential MoV-MB diameter <1.0 mm (i.e., MoV diameter <4.0 mm). Because proximal expansion cannot exceed 1.0 mm with the Ab without risk for fracture, fractal law (7) predicts that 76% of epicardial coronary bifurcations are treatable using the Ab BVS with a re-POT sequence.
Late recoil with the Ab BVS
Published data indicate a late recoil phenomenon specific to resorbable stents (12). The present study confirmed this, with moderate late recoil of just 3.3 ± 1.0% with the 2.5-mm Ab and 1.8 ± 1.2% with the 3.5-mm Ab at 1 h and no significant variation at 24 h. This recoil seemed to concern the stent as such rather than the bench models. Late recoil, however, was never very great.
The main limitation of this study lay in the use of coronary bifurcation bench models (18). However, the models adhered to fractal geometry and had 1- to 2-mm concentric thickness, so as to provide parietal elasticity comparable with that of an atherosclerotic arterial wall, as in case of hypocellular or dense fibrosis (700 to 1,500 kPa) (19,20).
The dimensions and geometry specified at the design stage are systematically altered by the polymerization process, leading to retraction at unmolding. Each bench model was therefore measured ahead of each test; the linear fractal ratio was 0.69, compared with a theoretical value of 0.678 (7,21).
The fractal bifurcations bench models did not model associated lesions: the study objective concerned the behavior of the Ab BVS implanted using the re-POT sequence, although it is indeed recommended to optimize lesion dilation ahead of BVS implantation (1–4).
In provisional bifurcation scaffolding, BVS deformation is limited by intrinsic reduction of the polymer’s elongation at break. Two fractal coronary bifurcation bench models (LAD-like and LM-like) were used for 40 comparisons of re-POT effects between the polymeric Ab scaffold and the metallic XX stent. The re-POT sequence optimized provisional coronary bifurcation treatment with the Ab BVS in most cases, respecting fractal geometry and scaffold integrity on condition that proximal differential diameter did not exceed 1.0 mm; strut fracture was then negligible. Clinical studies using OCT imaging will be needed to replicate the present geometric results.
WHAT IS KNOWN? In provisional bifurcation scaffolding, BVS deformation is limited by intrinsic lowering of the fracture threshold of the semicrystalline polymer; final KBI is thus not feasible.
WHAT IS NEW? A sequence of POT, SB inflation, and final POT, called re-POT, seems the best adapted. In these fractal bifurcation bench tests, the re-POT sequence optimized provisional coronary bifurcation treatment with the Ab BVS in most cases, respecting fractal geometry and scaffold integrity on condition that proximal differential diameter did not exceed 1.0 mm.
WHAT IS NEXT? The present results encourage implementation of the re-POT sequence in BVSs in clinical practice; clinical trials should be undertaken.
For supplemental videos and their legends, please see the online version of this article.
Abbott Vascular provided all bioresorbable vascular scaffold and metallic stent samples, unconditionally. All authors have reported they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- bioresorbable vascular scaffold
- kissing balloon inflation
- left anterior descending coronary artery
- left main coronary artery
- main branch
- mother vessel
- optical coherence tomographic
- proximal optimizing technique
- side branch
- side branch obstruction
- XIENCE Xpedition
- Received January 19, 2016.
- Revision received March 15, 2016.
- Accepted April 7, 2016.
- American College of Cardiology Foundation
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