Comparison of Side-Branch Dilation Techniques After Resorbable Magnesium Scaffold Implantation: A Bench Study

Abstract: Background. The resorbable magnesium scaffold (RMS) has demonstrated a good safety profile to treat de novo lesions. Nevertheless, bifurcation lesions involving a side branch (SB) >2.0 mm in diameter were excluded from these studies, and such lesions remain technically challenging due to concerns of scaffold deformation or fracture. We sought to evaluate different SB dilation strategies after provisional T-stenting strategy with RMS using silicon bifurcation phantoms. Methods and Results. Three different strategies were compared: proximal optimization technique (POT)-side-rePOT (rePOT), kissing-balloon inflation (KBI), and mini kissing-balloon inflation (MKBI) strategies. Strut and connector fractures were evaluated by micro computed tomography and apposition by optical coherence tomography (OCT). Twelve Magmaris scaffolds (Biotronik) were successfully implanted (4 in each group). There was no difference in strut and connector fractures among the three techniques, as no fracture was visualized. OCT demonstrated that MKBI significantly decreased global malapposition following SB inflation as compared with rePOT or KBI strategies (95.3% vs 88.3% of perfectly apposed struts [P<.001] and 93.6% [P<.01], respectively, for MKBI vs rePOT and KBI). After step-by-step over-expansion of 6 RMS devices with 3.75 mm, 4.0 mm, and 4.5 mm NC balloons at 16 atm (ie, +1.5 mm from the initial 3.0 mm RMS), no strut or connector fracture could be visualized. Conclusion. Provisional single-stent technique with the Magmaris RMS on a bifurcation lesion is technically feasible with these three different strategies without scaffold fracture. MKBI strategy resulted in better apposition rates as compared with KBI or rePOT strategies. Nevertheless, Magmaris use in bifurcation lesions should not be advised before similar results are confirmed by in vivo studies.

J INVASIVE CARDIOL 2019;31(8):E249-E255.

Key words: coronary bifurcation, Magmaris, resorbable magnesium scaffolds, RMS

The bioresorbable scaffold (BRS) is a recent and promising technology that allows provisional scaffolding of the coronary artery. Although first-generation BRS devices did not show improved results as compared with the latest generation of drug-eluting stents,¹ the interest in such technology is still growing.² New devices composed of different platforms, such as the resorbable magnesium scaffold (RMS), have already been implanted in humans for non-bifurcation coronary lesions, although bifurcation lesions might be considered as well after careful evaluation in vitro, in vivo, and in clinical studies. Indeed, the RMS has demonstrated a good safety profile to treat de novo lesions at 6, 12, and 24 months of follow-up.^3,4 Nevertheless, bifurcation lesions involving a side branch (SB) >2.0 mm in diameter were excluded from these studies. Such lesions account for at least 15% of all percutaneous coronary interventions (PCIs) and remain technically challenging due to concerns of scaffold deformation or fracture⁵ and suboptimal SB results. Based on the recent literature, provisional T-stenting of the main branch (MB) remains the default approach for most bifurcation lesions.⁶ The differences between metallic and resorbable scaffolds have led us to re-examine our technique for bifurcation dilation. Indeed, the first-generation Absorb BRS (Abbott Vascular) was not advised for bifurcation lesions involving a SB >2.0 mm in diameter. Nevertheless, multiple registries involving bifurcation lesions and bench testing demonstrated connector and strut fractures.⁷

RMS implantation in bifurcations under optical coherence tomographic (OCT) guidance was successfully performed and reported in a few in vivo cases.^8,9 Nevertheless, the safety and efficacy of SB dilation are not yet proven, and this strategy is not advised by the manufacturer, as it could cause distortion similar to that seen in first-generation BRS devices and metallic stents. While MB postdilation and kissing-balloon inflation (KBI) can correct metallic stent distortion,¹⁰ the efficacy and safety of postdilation strategies for RMS distortion are uncertain. Moreover, there could be some concern that the simultaneous inflation of two balloons during KBI may cause significant RMS damage.

The availability of RMS in an increasing number of catheterization laboratories will most likely result in a more liberal use of the device, perhaps leading to the idea that the manufacturer recommendations are excessively restrictive. Coupled with the rush for originality typically accompanying new technology, the lack of knowledge on the actual deformation capability of magnesium BRS might be clinically harmful. Therefore, by using micro computed tomography (micro-CT) to detect strut and connector fractures and OCT to evaluate scaffold apposition, the purpose of this bench study was to evaluate different SB dilation strategies after provisional T-stenting strategy with RMS on bifurcation phantoms.

Methods

Device description. The Magmaris RMS (Biotronik) is a magnesium balloon-expandable BRS mounted on a rapid-exchange delivery system. It is made of a completely radiolucent absorbable magnesium alloy coated with a poly-L-lactic acid biodegradable polymer eluting sirolimus¹¹ (1.4 µg/mm² of the scaffold surface), except for two radiopaque markers at the distal and proximal ends of the scaffold (Figure 1). The scaffold design consists of six in-phase sinusoidal hoops/rings linked by two straight mid-strut connectors (six-crown, two-link, open-cell design), with both strut thickness and width of 150 µm. The cell perimeter is 19.3 mm for the 3.0 mm scaffold and 20.6 mm for the 3.5 mm scaffold. The calculated maximum circular diameter of a cell is 6.1 mm for the 3.0 mm scaffold and 6.6 mm for the 3.5 mm scaffold. Approximately 95% of the magnesium is expected to be absorbed within 12 months. The recommended maximum expansion diameter of the Magmaris RMS is limited to 0.6 mm above the nominal diameter. Beyond this limit, strut fracture or scaffold mechanical property deterioration can happen, which could be critical to long-term device function, even in the absence of fracture.

Bifurcation phantoms. In vitro experiments were performed under fluoroscopy in the catheterization laboratory. We used two types of silicon fractal geometry bifurcation phantoms with angles of 60° (n = 6) and 30° (n = 6) (Segula Technologies). According to fractal law, bifurcation phantom geometry was 3.5 mm lumen diameter in the mother vessel (MoV), 2.85 mm lumen diameter in the MB, and 2.35 mm lumen diameter in the SB. Phantom models had elastic properties that allowed stretching of the material beyond the nominal diameter.

Bifurcation dilation strategies. Three different bifurcation strategies were compared: (1) POT-side-rePOT (rePOT) strategy; (2) KBI; and (3) mini kissing-balloon inflation (MKBI).

The rePOT sequence, which has been increasingly performed in our daily practice, consists of a first proximal optimizing technique (POT) with a non-compliant (NC) balloon, followed by SB dilation and rePOT. This sequence optimizes the final result of provisional T-stenting, maintaining circular geometry while significantly reducing SB ostium strut obstruction, risk of SB occlusion, and global strut malapposition. The KBI technique consists of the juxtaposition of two NC balloons in the MB and the SB, with the two balloons overlapping in the MoV for approximately half of the SB balloon length and diameters sized according to Mitsudo’s formula¹² (MoV = MB2 + SB2). A final POT is usually performed in order to restore proximal stent circularity and reduce strut malapposition after KBI, according to clinical best practice.¹³ The MKBI technique reproduces KBI, but with minimal overlap of balloons, placing the proximal marker of the SB balloon in the MB immediately proximal to the SB ostium, and with low-pressure inflation, in order to avoid significant elliptical over-expansion of the MV lumen.¹⁴ Balloon diameters are sized according to the MoV and SB diameters.

Procedures. All procedures were performed under fluoroscopy in the catheterization laboratory. The first step consisted of three different bifurcation strategies and the second step consisted of step-by-step proximal over-expansion (Figure 2).

(1) Bifurcation strategies. First, systematic wiring of the two distal branches was done at the beginning of the procedure. The Magmaris scaffolds used were 3.0 mm in diameter and ranged from 15-25 mm in length. They were deployed in the MB up to 12 atm in a way to completely cover the SB with at least 8 mm in the MoV, regardless of the scaffold length (n = 12). The first POT was performed using a short 3.5 mm NC balloon inflated to 16 atm. The distal balloon marker was positioned in front of the carina and the proximal part was still in the scaffold. Assuming that SB flow was compromised, wires were exchanged while trying to rewire the SB through the most distal cell by the pullback rewiring technique. SB dilation across the strut with a 2.5 mm NC balloon inflated to 16 atm was performed. Thereafter, the three strategies were performed in four models (two 30° angle models and two 60° angle models) as follows:

(a) RePOT scenario: After SB dilation across the strut with a 2.5 mm NC balloon up to 16 atm, a rePOT with a 3.5 mm NC balloon at 16 atm was performed.

(b) KBI scenario: Using Mitsudo’s formula (MoV = MB2 + SB2), we calculated a combined diameter of 2.75 mm for the MB and 2.25 mm NC short balloons for the SB, with symmetric inflation pressure up to 12 atm. The proximal MB was then reoptimized by a final POT with a 3.5 mm NC balloon at 16 atm.

(c) MKBI scenario: MKBI was carried out using 3.5 mm and 2.25 mm NC balloons in the MB and the SB, respectively, with minimal overlap and inflated slowly to 5 atm. The proximal MB was then reoptimized by a final POT with a 3.5 mm NC balloon inflated to 16 atm.

OCT was performed to determine strut malapposition and micro-CT was used to determine fracture (location and type). All balloons used were NC Trek devices (Abbott Vascular). Each inflation of the RMS was performed stepwise up to 12 atm, which was then maintained for 30 seconds.

(2) Step-by-step proximal over-expansion. In six models, a final over-expansion POT was carried out with different incremental NC balloons (3.75 mm, 4.0 mm, and 4.5 mm), inflated up to 16 atm over 30 seconds. Scaffolds were then reinspected on micro-CT after each over-expansion.

OCT analysis. OCT imaging was performed in each case, at 10 mm/s pullback speed using OCT Dragon Duo imaging catheters (Abbott) and analyzed using a dedicated workstation. Images were recorded at 100 frames/s in 0.1 mm sections. For descriptive purposes, analyses of the imaging data were performed by dividing each bifurcation into six different areas. Analyses were performed by an experienced OCT operator who was independent from the study operators. OCT analysis consisted of distance measurements between each stent strut and the inner phantom wall throughout the bifurcation area divided into four parts (MB ostial, MB abostial, SB ostial, and SB abostial) slice per slice. Two parts distal to the bifurcation area (proximal MoV and distal MB) were similarly evaluated every millimeter. Apposition was graded as follows: (1) perfect apposition (<100 µm); (2) incomplete apposition (100-200 µm); (3) marked malapposition (malapposition ≥200 µm); or (4) floating struts (malapposition ≥500 µm), as reported in previous studies.^15,16

Micro-CT. Each model was scanned using a high-resolution x-ray micro-CT device (Quantum FX Caliper; Life Sciences). Acquisitions were performed with a field of view that was 10 mm in diameter, using an isotropic voxel size of 20 x 20 x 20 µm³ (90 kV; 160 µA; 180 s). These two-dimensional (2D) images were processed using HorosR software to create three-dimensional (3D) reconstructions (Figure 3 and Video 1). The 2D and 3D micro-CT analyses were assessed for the MoV, MB, SB, and bifurcation segments separately. For each segment, the presence and location of strut fractures (hoop or connector) were reported. Fracture was defined as loss of continuity in the scaffold on the 3D reconstruction.

Statistical analysis. All categorical variables are expressed as mean ± standard deviation, median value, or count (percentage). Continuous variables were compared with the non-parametric Mann-Whitney test; a P-value <.05 was considered statistically significant. All statistical analyses were performed using Prism, version 7.0 (Graphpad).

Results

Procedural success. All 12 Magmaris scaffolds were successfully implanted with proximal optimization. We did not experience difficulty for the SB rewiring, with no differences between 30° and 60° angles. SB inflation induced visual malapposition of the stent at the MB ostium, and all three techniques rectified this malapposition. During SB dilation in one of the rePOT 30° angle cases, we detected a longitudinal compression of the proximal part of the RMS scaffold during the passage of the first SB balloon.

Bifurcation strategies. A total of 900 connectors and 450 rings were analyzed. There was no difference in strut and connector fractures among the three techniques, as no fracture was visualized. Regarding apposition, OCT demonstrated that the MKBI sequence significantly decreased global malapposition following SB inflation with better perfect apposition as compared with the rePOT or KBI strategies (95.3% vs 88.3% [P<.001] and 93.6% [P<.01], respectively, for MKBI vs rePOT and KBI) (Table 1). These benefits were obtained without scaffold fracture, as shown in the micro-CT analysis. Significant differences in strut apposition between MKBI and rePOT were localized at each segment of OCT analysis, except for MB abostial bifurcation and distal MB, whereas significant differences were only localized at MB bifurcation ostial and SB bifurcation abostial between MKBI and KBI (Table 1 and Figure 4). Better strut apposition with the KBI strategy was also observed as compared with the rePOT strategy (93.6% vs 88.3%; P<.001).

Step-by-step proximal over-expansion. After step-by-step over-expansion of six RMS devices with 3.75 mm, 4.0 mm, and 4.5 mm NC balloons at 16 atm (ie, +1.5 mm from the initial 3.0 mm RMS), no strut or connector fracture could be visualized.

Discussion

This bench study sought to compare three techniques to correct scaffold distortion after provisional T-stenting technique with different SB angles on 12 bifurcation bench models. It showed that provisional T-stenting with SB dilation using Magmaris RMS is technically feasible with these three different bifurcation strategies. There was no difference among techniques in terms of strut and connector fracture. In one model, a longitudinal compression of the proximal MoV scaffold occurred during the passage of the first SB balloon. This could be in part explained by the fact that we utilized already used balloons, with poor crossing profiles. Nevertheless, RMS crossing should be carefully performed, if possible with new balloons in order to avoid proximal compression. Indeed, provisional stenting with KBI was already performed in an in vivo rabbit model (n = 5) and all procedures produced good results on 3D micro-CT assessment with scaffolding of all segments and good SB aperture. Moreover, in accordance with the present study, no strut fracture was identified.⁹

Regarding apposition, these three postdilation strategies optimized provisional coronary bifurcation treatment, with significantly better apposition with the MKBI sequence, in respect to scaffold integrity.

These findings are consistent with a recent study by Liu et al,¹⁷ who demonstrated that whereas KBI rectified the MoV stent malapposition, it resulted in stent deformation and over-expansion, and led to a “bottleneck” effect, which could not be rectified by POT. In contrast, MKBI also rectified the MoV stent malapposition, without notable stent deformation, over-expansion, or bottleneck. In all cases, POT optimized the MoV strut apposition. MKBI seems also feasible with RMS and should therefore be advised over KBI to avoid over-expansion of the scaffold. On the basis of these observations, even if not recommended in such a situation (ie, for bifurcation lesions), SB dilation should be performed using MKBI if RMS devices are to be used in provisional T-stenting. In all cases, proper postdilation and POT of the Magmaris RMS are crucial, but can also be challenging as struts cannot be easily visualized by angiography. Therefore, systematic intracoronary imaging using OCT should be performed at the end of implantation to ensure perfect apposition.

After step-by-step proximal over-expansion up to 1.5 mm from the initial RMS size, no fracture was detected on micro-CT in any of the six models. The current recommendation for Magmaris postdilation is limited by the manufacturer to 0.6 mm. The fact that no fracture could be visualized up to 1.5 mm postdilation is reassuring in regard to the device’s mechanical properties. Nevertheless, we know that scaffold mechanical property deterioration can happen beyond the 0.6 mm maximum functional diameter limit, even in the absence of fracture. Therefore, our data are reassuring regarding the scaffold strength, but over-dilation cannot be advised.

Study limitations. The main limitation of this study lies in the small number of bifurcation models. Furthermore, the use of coronary bifurcation bench phantom does not perfectly model a real bifurcation lesion. Nevertheless, our bench models are specifically designed for this kind of study, and had elastic properties that allow stretching of the scaffold, calculated to be comparable to an atherosclerotic arterial wall. Another limitation of bench studies is that the deterioration of scaffold mechanical properties, without fracture, cannot be explored by OCT and micro-CT. In addition, OCT analysis was performed only one time, immediately after scaffold postdilation, whereas late recoil could happen, in vivo, a few hours after implantation.^18,19 In addition, strut presence in the SB ostium lumen area and elliptical scaffold deformation were not evaluated, and this was previously reported to impact fluid dynamics and parietal stress distribution.²⁰ Last, our study focused on SB dilation technique, and does not give insight into two-stent bifurcation strategies. Clinical studies using OCT will be needed to evaluate whether the better apposition rate of the Magmaris RMS is correlated with reduced scaffold thrombosis rates, as previously described for drug-eluting stents.²¹ Before clinical studies, computational fluid dynamic studies could give us interesting experimental information about the consequences of the Magmaris malapposition rate on flow patterns and the velocity stream.

Conclusion

Our study suggests that a provisional single Magmaris stent PCI technique on a bifurcation lesion is technically feasible with these three different strategies (rePOT, KBI, and MKBI) without scaffold fracture. MKBI strategy resulted in better apposition rates as compared with KBI and rePOT strategies. Based on the results of our study, we would therefore suggest that the MKBI strategy should be the technique of choice if an RMS is to be used in provisional T-stenting. Nevertheless, Magmaris use in bifurcation lesions is not advised until such experimental results are confirmed by in vivo studies.

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From the ¹Department of Cardiology, Hôpital Cochin, AP-HP, Paris, France; ²Department of Cardiology, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; and ³Université Paris Descartes, Faculté de Médecine, Paris, France.

Funding: This study was an independent, investigator-initiated study. This research was performed with the support of Biotronik, Bulach, Switzerland (Magmaris RMS devices were provided by Biotronik).

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr de Hemptinne reports personal fees from Biotronik. Dr Picard reports personal fees from B. Braun, Biotronik, Bristol Myers Squibb, and Sanofi. Dr Varenne reports personal fees from Abbott Vascular, Biotronik, and Boston Scientific. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted February 20, 2019, accepted March 4, 2019.

Address for correspondence: Fabien Picard, MD, MSc, Hopital Cochin, Département de Cardiologie, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. Email: Fabien.picard@aphp.fr