Impact of Implantation Technique and Plaque Morphology on Strut Embedment and Scaffold Expansion of Polylactide Bioresorbable Scaffold　– Insights From ABSORB Japan Trial –

Abstract

Background: The optimal implantation technique for the bioresorbable scaffold (Absorb, Abbott Vascular) is still a matter of debate. The purpose of the present study was to evaluate the effect of implantation technique on strut embedment and scaffold expansion.

Methods and Results: Strut embedment depth and scaffold expansion index assessed by optical coherence tomography (OCT) (minimum scaffold area/reference vessel area) were evaluated in the ABSORB Japan trial (OCT subgroup: 87 lesions) with respect to implantation technique using either quantitative coronary angiography (QCA) or OCT. Strut embedment was assessed at the strut level (n=667), while scaffold expansion was assessed at the lesion level (n=81). The mean embedment depth was 63±59 µm. Balloon sizing and inflation pressure had no direct effect on strut embedment. Plaque morphology affected strut embedment [nonatherosclerotic (58.9±54.3 µm), fibroatheroma (73.3±59.6 µm), fibrous plaque (59.7±51.1 µm), and fibrocalcific plaque (–3.1±61.6 µm, negative value means malapposition), P <0.001]. The balloon-artery ratio positively correlated with the expansion index. This relationship was stronger when the OCT-derived reference vessel diameter (RVD) was used as a reference for balloon selection rather than the QCA-derived one [predilatation (Pearson correlation r: QCA: 0.167 vs. OCT: 0.552), postdilatation (QCA: 0.316 vs. OCT: 0.717)].

Conclusions: Underlying plaque morphology influenced strut embedment, whereas implantation technique had no direct effect on it. Optimal balloon sizing based on OCT-derived RVD might be recommended. However, the safety of such a strategy should be investigated in a prospective trial. (Circ J 2016; 80: 2317–2326)

Acute performance of the bioresorbable vascular scaffold (Absorb BVS, Abbott Vascular, Santa Clara, CA, USA) has been evaluated in comparison with metallic stents (XIENCE; Abbott Vascular) in several randomized controlled trials.^1–4 The acute gain by quantitative coronary angiography (QCA) was consistently larger with the XIENCE than the Absorb BVS, which could be partially derived from the difference in mechanical properties. Some of the data from registry and randomized controlled trials demonstrated that under-expansion was associated with late clinical events following scaffold implantation.⁵ A dedicated implantation technique has been thought to be necessary for implantation of the Absorb BVS to achieve similar acute performance as obtained with metallic stents,⁶ but it is yet to be consolidated.

The Absorb BVS has a larger surface area (27%) than the XIENCE metallic stent (13%).⁷ When the same force is applied, a device with a larger contact area would generate a lower pressure to the vessel wall according to the simple principle: pressure=force/area. Accordingly, the larger footprint of the wider struts of the Absorb BVS could result in less strut embedment and smaller expansion of the device and vessel even if the same force as for metallic stents is applied.⁸ Less embedment and more protrusion of the struts into the lumen could create some unfavorable microenvironments, such as low endothelial shear stress zones upstream and downstream to the struts, which could cause more thrombogenic conditions and delayed neointimal coverage of the struts. Well-embedded struts would not cause such unfavorable conditions and could lead to better clinical outcomes. However, the relationship between the predilatation, postdilatation and strut embedment remains to be investigated.

In the present study, we retrospectively evaluated the degree of strut embedment and scaffold expansion according to lesion parameters assessed by optical coherence tomography (OCT), and QCA, as well as the procedural parameters.^8,9

Methods

Study Subjects

ABSORB Japan was a prospective, multicenter, randomized, single-blind, active-controlled clinical trial in which 400 patients undergoing coronary stent implantation in Japan were randomized in a 2:1 ratio to treatment with the Absorb BVS or the XIENCE Prime/Xpedition.¹ The details of the trial have been described elsewhere.¹ In the present investigation, we analyzed the baseline OCT data of the Absorb BVS arm of the OCT group 1 (125 patients), in which patients underwent postprocedural OCT. The study was conducted according to the Declaration of Helsinki. Prior to initiating the study, the institutional review board at each investigational site approved the clinical trial protocol. All patients provided written informed consent before enrolment.

Procedural Details

Per the protocol of the ABSORB Japan trial, predilatation was mandatory. The recommended balloon size was 0–0.5 mm smaller than visual assessment of the maximal lumen diameter (Dmax).⁵ Rotational atherectomy was not allowed. Postdilatation was left to the operators’ discretion. When postdilatation was performed, high-pressure postdilatation with up to 0.5 mm larger noncompliant (NC) balloon than the nominal device size was recommended. In the current analysis, for the predilatation balloon, if it was >0.25 mm smaller than the reference vessel diameter (RVD), it was defined as small. If the balloon was larger than, equal to, or smaller by ≤0.25 mm than the RVD, it was defined as a large balloon. Regarding the postdilatation, if the balloon was smaller than, equal to, or larger by <0.25 mm than the RVD, it was defined as small. If the balloon was ≥0.25 mm larger than the RVD, it was defined as a large balloon. OCT was performed at the end of the procedure. After observation by OCT, if needed additional postdilatation was allowed at the operators’ discretion. In such cases, OCT was repeated at the completion of the procedure.

Assessment of the Relationship Between Implantation Technique and Embedment Depth

The endpoints of interest in the present study included the strut embedment depth and scaffold expansion post Absorb BVS implantation assessed by OCT. The Absorb BVS was implanted according to the standard protocols at the discretion of the operators.¹ Pre- and postdilatation balloons were categorized into 3 groups: semicompliant (SC), NC, and cutting/scoring (CB). Embedment depth was stratified by balloon type, balloon inflation pressure, and balloon sizing with reference to the RVD assessed by either QCA or OCT at postimplantation.¹⁰ The degree of scaffold expansion was assessed as a scaffold expansion index defined as the ratio of postprocedural minimum endoluminal scaffold area to the reference vessel area. This parameter was previously applied for IVUS assessment.^10,11

OCT

OCT pullbacks were obtained at the very end of the procedure by a frequency-domain C7 system using a Dragonfly^TM catheter (n=5) (St. Jude Medical Inc, Saint Paul, MN, USA), a frequency-domain ILUMIEN OPTIS system using a Dragonfly^TM Duo catheter (n=61) (St. Jude Medical), or an optical frequency-domain imaging (OFDI) TERUMO Lunawave console using a FastView catheter (n=15) (Terumo Europe, Leuven, Belgium).¹² The OCT analysis was performed with newly developed specific software (QCU-CMS software version 4.69; Leiden University Medical Center, Leiden, The Netherlands).⁹ The scaffold segment analysis was performed every 200 μm cross-section in the case of OCT and every 250 μm in the case of OFDI. The following parameters were evaluated: lumen area, abluminal and endoluminal scaffold areas, and embedment depth.^8,9 The embedment depth of each strut was automatically measured by the dedicated software.⁹ The mean embedment depth at the lesion level is reported. In cases without postdilatation, the device balloon can expand the scaffold uniformly, whereas in cases with postdilatation, even though balloon dilatation was performed, it does not necessarily mean that whole scaffold was uniformly expanded by the postdilatation balloon. Therefore, the minimum scaffold area (MSA) cross-section was selected as a region of interest in order to make sure that balloon dilatation was performed exactly at that cross-section. The embedment depth of each strut and the mean embedment depth in each MSA cross-section were computed.

To investigate the possible relationship between the degree of embedment and plaque morphology in scaffolded segments, underlying plaque characterization of the BVS struts was qualitatively assessed in postscaffold implantation OCT images. Offline OCT analysis was performed using QCU-CMS by 3 independent observers (Y.S., Y.O., and T.A.). Any disagreement between observers was resolved by consensus. Lipid was defined as a signal-poor region within a plaque, with poorly delineated borders and a fast drop-off in OCT signal, whereas calcium was defined as a signal-poor region, but with sharply delineated borders and a gradual drop-off in OCT signal.¹³ The plaque underlying each strut in the region of interest was classified into 4 different types: nonatherosclerotic, fibroatheroma (either thin or thick cap fibroatheroma), fibrocalcific, and fibrous.¹⁴ Nonatherosclerotic plaque was defined as a 3-layered architecture of the vessel wall, with no or little evidence of intimal thickening. Fibroatheroma was defined as plaque with evidence of OCT-defined lipid pool, where the lipid arc was ≥90°. Fibrocalcific plaque was defined as evidence of calcification and any lipid-pool arc was ≤90°. Fibrous was defined as plaque not meeting either fibroatheroma or fibrocalcific definition. For the cross-section level analysis, the predominant plaque type was selected when several plaque types were identified in 1 cross-section.

Statistical Analysis

Data are expressed as mean±standard deviation or median and interquartile range with differences [95% confidence interval]. Normality of distribution was tested by the Kolmogorov-Smirnov test. Mixed linear model with an assumed Gaussian distribution was used for comparisons of continuous variables to take into an account the clustered nature of >1 scaffolds analyzed from the same patients and >1 struts from the same scaffold, which might result in unknown correlations among measurements within the clusters. Simple linear regression analysis and Pearson’s correlation coefficient were used to evaluate the strength and direction of the linear relationship between the scaffold expansion index and balloon sizing. Statistical significance was assumed at a probability (P) value of <0.05. All statistical analyses were performed with SPSS (version 23.0.0, IBM, New York, NY, USA).

Results

Study Population

Of the 126 patients in the OCT subgroup 1, including 87 lesions from 83 patients in the Absorb BVS arm and 44 lesions from 43 patients in the XIENCE arm, the present study evaluated only the Absorb BVS arm. We obtained data for 81 lesions by corelab analysis and from 74 lesions for lesion-level embedment analysis according to the criteria described elsewhere.¹² Baseline clinical characteristics, lesion characteristics, and QCA results have been previously reported.¹² Procedural characteristics are summarized in Table 1. Results of postprocedural OCT are indicated in Table 2. There was no acute disruption in this cohort.

Table 1. Procedural Characteristics

	(L=81)
Preprocedural RVD by QCA (mm)*	2.70±0.45
Predilatation
Predilatation performed, n (%)	81 (100%)
Predilatation balloon type
Semicompliant balloon, n (%)	38 (47%)
Noncompliant balloon, n (%)	24 (30%)
Cutting/scoring balloon, n (%)	19 (24%)
Maximum predilatation nominal balloon diameter (mm)	2.79±0.37
Maximum predilatation balloon pressure (atm)	11.6±3.9
Expected maximum predilatation balloon diameter (mm)	2.87±0.37
Device
Maximum scaffold diameter (mm)	3.03±0.38
Maximum deployment pressure (atm)	10.4±3.0
Postdilatation
Postdilatation performed, n (%)	63 (78%)
Postdilatation balloon type
Semicompliant balloon, n (%)	16 (25%)
Noncompliant balloon, n (%)	47 (75%)
Maximum postdilatation nominal balloon diameter (mm)	3.15±0.44
Maximum postdilatation balloon pressure (atm)	15.0±4.1
Expected maximum postdilatation balloon diameter (mm)	3.28±0.45
Entire procedure
Maximum nominal balloon diameter throughout the procedure (mm)	3.14±0.43
Pressure at maximum balloon (atm)	16.2±4.9
Expected diameter of maximum balloon (mm)	3.20±0.46

Data are expressed as mean±standard deviation, n (%). *RVD by QCA was not available for 1 lesion. L, number of lesions; QCA, quantitative coronary angiography; RVD, reference vessel diameter.

Table 2. Results of Postprocedural OCT Analysis

	(L=81)
Reference vessel diameter (mm)*	2.95±0.54
Mean lumen diameter (mm)	3.03±0.42
(Projected) minimum lumen diameter (mm)	2.75±0.42
Mean lumen area (mm2)	7.37±2.01
Minimum lumen area (mm2)	6.09±1.81
Mean scaffold diameter (mm)†	3.11±0.43
(Projected) minimum scaffold diameter (mm)†	2.57±0.43
Mean scaffold area (mm2)†	7.74±2.10
MSA (mm2)†	6.55±1.99
Mean strut area (mm2)	0.27±0.04
Mean embedment depth per lesion (μm)	57±24 (L=74)
Mean embedment depth on MSA cross-section (μm)	64±35 (L=79)
Mean embedment depth per strut (μm)	63±59 (n=667)

Data are expressed as mean±standard deviation, percentage and number with 95% confidence interval. *Reference vessel diameter by OCT not available for 4 lesions. ^†“Abluminal” scaffold data. L, number of lesions; MSA, minimum scaffold area; OCT, optical coherence tomography.

Figure 1 indicates the proportions of small or large balloons used pre- and postdilatation in terms of balloon sizing with reference to the OCT-derived RVD. In 77 lesions with OCT reference data, predilatation with a large balloon was performed in 49 (64%) lesions, while the remaining 28 (36%) lesions were treated with a small balloon. Of the lesions treated with a large predilatation balloon, 27 (55%) lesions were treated with a large postdilatation balloon.

Figure 1.

Flowchart of pre- and post-dilatation balloon sizing. Balloon sizing at pre- and post-dilatation was stratified by relative diameter difference compared to reference vessel diameter (RVD) assessed by optical coherence tomography (OCT). Embedment depth and scaffold expansion index are expressed as mean±standard deviation.

Impacts of Implantation Technique and Plaque Morphology on Strut Embedment

In the present study, data from 79 lesions for MSA cross-section analysis were evaluated, with 2 lesions excluded because of insufficient image quality for assessment of strut embedment. In the MSA cross-section analysis, a total of 667 struts were used in the assessment of the relationship between implantation technique and embedment depth. The balloon type was not associated with the degree of strut embedment (predilatation: SC 65±36 µm, NC 63±37 µm, and CB 65±33 µm, P=0.98; postdilatation: SC 70±26 µm, and NC 61±36 µm, P=0.36). The embedment depth was numerically higher in the small predilatation balloon group than in the large predilatation balloon group, although it did not reach statistically significant difference (P=0.36) (Figure 1). The distribution of strut embedment is demonstrated in a histogram (Figure 2). The mean embedment depth was 63±59 µm [40% of the strut thickness of the Absorb BVS (157 µm)]. The impact of implantation technique at pre- and postdilatation on strut embedment is illustrated as bar graphs (Figure 3). Balloon sizing and inflation pressure had no direct effect on strut embedment, although high-pressure postdilatation (≥20 atm) resulted in numerically deeper embedment than low-pressure postdilatation. Balloon type did not present any significant effect on strut embedment at predilatation (P=0.58) or postdilatation (P=0.17).

Figure 2.

Distribution of strut embedment.

Figure 3.

Bar graphs of the impact of implantation technique on strut embedment depth with reference to the reference vessel diameter (RVD) by QCA (Upper panel)/OCT (Middle panel) and inflation pressure (Lower panel) at pre- (Left column) and postdilatation (Right column) assessed at the strut level. Data are shown as mean±standard error. OCT, optical coherence tomography; PreD, diameter of predilatation balloon; PostD, diameter of postdilatation balloon; QCA, quantitative coronary angiography.

Correlation assessment between embedment depth and plaque morphology (Figure 4) showed that struts were better embedded in fibroatheroma (73.3±59.6 µm) than in a nonatherosclerotic vessel (58.9±54.3 µm) or fibrous plaque (59.7±51.1 µm). Absorb BVS struts appeared difficult to embed in fibrocalcific plaque [−3.1±61.6 µm, (negative value means malapposition) P<0.001].

Figure 4.

Correlation between strut embedment depth and plaque morphology: nonatherosclerotic vessel (A), fibroatheroma (B), fibrocalcific plaque (C), and fibrous plaque (D). Data are shown as box-whisker plots and mean±standard deviation.

Impact of Implantation Technique on Scaffold Expansion

The balloon type was not associated with the degree of scaffold expansion (predilatation: SC 0.75±0.13, NC 0.71±0.16, and CB 0.70±0.11, P=0.17; postdilatation: SC 0.77±0.12, and NC 0.79±0.20, P=0.77). The most aggressive technique (combination of large predilatation balloon with large postdilatation balloon) resulted in the highest scaffold expansion index (0.89±0.16), whereas less aggressive predilatation without postdilatation led to the lowest scaffold expansion index (0.67±0.13) (P<0.001) (Figure 1). Dissection length did not differ with these different implantation techniques (P=0.46).

The difference between balloon size and OCT-derived RVD correlated with the scaffold expansion index (Figure 5). A similar relationship was observed for the QCA-derived RVD. However, OCT showed better correlation than QCA on both predilatation balloon (Pearson correlation r: QCA 0.167 vs. OCT 0.552) and postdilatation balloon (Pearson correlation r: QCA 0.316 vs. OCT 0.717). Inflation pressure did not correlate with the scaffold expansion index. Figure 6 illustrates the correlation between scaffold expansion and balloon sizing with reference to the RVD assessed by OCT. To obtain a similar expansion index as for the XIENCE metallic stent (mean value, 0.76; data from the ABSORB II trial),¹¹ at predilatation, a balloon with 0.25 mm smaller or equal diameter with reference to the RVD was necessary, while at postdilatation, 0.25 mm larger or more was warranted.

Figure 5.

Bar graphs showing the impact of balloon sizing in implantation technique with reference to the reference vessel diameter (RVD) by QCA (Upper panel)/OCT (Middle panel) and inflation pressure (Lower panel) at pre- (Left column) and postdilatation (Right column) on scaffold expansion index assessed at the lesion level. Data are shown as mean±standard error. OCT, optical coherence tomography; PreD, diameter of predilatation balloon; PostD, diameter of postdilatation balloon; QCA, quantitative coronary angiography.

Figure 6.

Correlation between scaffold expansion and balloon sizing with reference to the reference vessel diameter (RVD) assessed by OCT. Scatter plots indicate that the scaffold expansion correlated well with balloon sizing at pre- and postdilatation. To obtain a similar expansion index to that of the XIENCE metallic stent (mean value of 0.76: data from the ABSORB II trial), at pre-dilatation, 0.25 mm smaller or equal diameter with reference to the RVD would be recommended, whereas at post-dilatation, 0.25 mm larger or more would be recommended. MSA, minimum scaffold area; OCT, optical coherence tomography. *Average of mean lumen diameter at 5 mm proximal and 5 mm distal to the scaffolded segment.

Discussion

The main findings of the present study can be summarized as follows: (1) mean embedment depth of the Absorb BVS struts was 63±59 µm (relative embedment ratio as per strut thickness: 40%); (2) underlying plaque morphology had a strong effect on strut embedment, whereas balloon sizing and inflation pressure appeared to have no direct effect; and (3) balloon sizing by OCT demonstrated a stronger correlation with scaffold expansion than that by QCA at both pre- and postdilatation.

Several previous randomized controlled trials have demonstrated that the acute gain by QCA is larger with the XIENCE metallic stent than with the Absorb BVS, which could be partially explained by differences in their mechanical properties.^1–4 When we apply the same force, struts with a larger “footprint” will theoretically result in a lower “penetrating” pressure, which explains the smaller expansion and worse embedment of the Absorb BVS with its large footprint (27%) as compared with the small footprint (13%) of the XIENCE.⁷ Accordingly, a dedicated implantation technique needs to be used for implantation of the Absorb BVS to achieve a similar acute performance as the metallic stent. In a study by Puricel et al, it was retrospectively demonstrated that there was a lower incidence of scaffold thrombosis with application of a BVS-dedicated implantation strategy (shown below) than with the conventional strategy:¹⁵ (1) predilatation with a NC balloon up to the same size as the RVD; (2) BVS implantation only in cases of full expansion of the NC balloon as demonstrated by angiography in 2 orthogonal planes; (3) implantation of a BVS of the same size as the RVD at 10–12 atm; (4) postdilatation with NC balloons up to a maximum of 0.5 mm larger at 14–16 atm. However, this specific strategy relied on a few mechanical assumptions that need to be evaluated in a prospective randomized fashion.

In the current series, the type of the balloon used for the predilatation did not affect expansion of the scaffold. In a previous publication by Sadamatsu et al, lesion preparation with a CB balloon achieved equivalent stent expansion to a NC balloon, even with lower pressure and a smaller diameter balloon than the NC balloon.¹⁶ In the current study, the balloon type and size selected by the operator were potentially influenced by the assessment of angiographic calcification. The CB and NC balloons were likely used for lesions with hard plaque, which could confound the results of our analysis.

The current analysis showed that large postdilatation balloons were associated with better scaffold expansion, whereas no significant association with the level of inflation pressure could be observed. In contrast, previous studies suggested that beyond sizing, the inflation pressure and duration of the postdilatation also play a role. Regarding the inflation pressure, Dirschinger et al demonstrated that high-pressure postdilatation (15–20 atm) with a NC balloon significantly improved acute lumen gain compared with low-pressure dilatation (8–13 atm).¹⁷ As for inflation time, Hovasse et al reported that a longer duration of stent balloon inflation (>25 s) significantly improved stent expansion compared with a shorter duration (5 or 15 s).¹⁸ Repeated balloon expansion also improved stent expansion.¹⁹ Kitahara et al recently demonstrated with various metallic platforms assessed by real-time OCT in an in-vitro silicon model that multiple short inflations achieved a larger final stent area than a single long inflation at postdilatation.²⁰ In the current study, balloon inflation time and number of balloon inflations were not analyzed because of the lack of those data in the trial. This point needs to be investigated in future trials.

Optimization of Scaffold Expansion

In the present study, the difference between balloon size and RVD positively correlated with the scaffold expansion index. In other words, the balloon-artery ratio positively correlated with the expansion index. This relationship was stronger if the OCT-derived RVD was used as a reference for balloon selection rather than the QCA-derived one [predilatation (Pearson correlation r: QCA 0.167 vs. OCT 0.552), postdilatation (QCA 0.316 vs. OCT 0.717)]. Angiographic assessment (QCA) reportedly underestimates the vessel diameter by 9.1% compared to OCT assessment as a gold standard for the measurement of lumen dimension.^12,21,22 Considering the fragility and delicacy of poly (L-lactide) compared with metal, more accurate sizing of the pre- and postdilatation balloons with OCT than with QCA might be essential for optimization of BVS implantation.²³

The current study demonstrated that essentially, use of larger pre- and postdilatation balloons improves scaffold expansion. As shown in Figure 6, when the expansion index of the XIENCE metallic stents observed in the ABSORB II trial was used as the reference of good expansion,¹¹ at pre-dilatation, 0.25 mm smaller or equal diameter with reference to the RVD would be recommended, while at post-dilatation, 0.25 mm larger or more would be advocated (Figure 1). Overexpansion was previously shown to pose a risk of acute disruption and dissection.²⁴ However, in the current series, there were no cases of acute disruption. In the ABSORB Cohort B trial, the mean balloon-artery ratio at postdilatation was 1.16±0.13, which resulted in excellent 5-year results without any unfavorable edge vascular responses.²⁵ In other words, a 3.48-mm postdilatation balloon could be used for a 3.0-mm RVD, at least for simple lesions. From that point of view, a 0.25-mm larger postdilatation using a NC balloon might be a practical guideline. However, the safety of such an implantation strategy for complex lesions should be investigated and confirmed in a prospective trial.

Optimization of Strut Embedment

Specific analysis of strut embedment revealed that the mean embedment depth was 63±59 µm (relative embedment ratio as per strut thickness: 40%) in the MSA cross-sections. Balloon type, balloon sizing, and balloon pressure did not present any significant correlation with strut embedment, whereas a strong effect of plaque morphology on strut embedment was clearly demonstrated. These results imply a difficulty in controlling strut embedment by implantation technique alone, and that strut embedment depends purely on scaffold design and the underlying plaque type.

Theoretically, struts that are well embedded into the vessel (ie, less protrusion of struts into the lumen) will less disturb the laminar blood flow, resulting in a smaller recirculation zone and low endothelial shear stress area than with less embedded struts.²⁶ As a consequence, the thrombogenic conditions surrounding the Absorb BVS could be mitigated. Well-embedded and less protruding struts can also lead to early neointimal coverage, which could prevent direct contact between blood and the high-thrombogenic products of the Absorb BVS (ie, proteoglycan) in the late phase, and thus mitigate the possibility of thrombus formation on the Absorb scaffold. Thus, good embedment is expected to overcome some of the drawbacks of the Absorb BVS. However, it appears difficult to make the Absorb struts embed well, which suggests 2 options: (1) improvement of the device itself (ie, thinner struts); or (2) sufficient lesion preparation and consequent sufficient expansion of the scaffold in order to avoid the scaffold underdeployment that could cause flow disturbance related to the dense distribution of the polymeric struts.^5,15 As the guideline from the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) describes, aggressive lesion preparation with rotational atherectomy or orbital atherectomy would be justified as lesion preparation before implantation of the Absorb BVS.^27,28 OCT-guided Absorb implantation could also be recommended for accurate device/balloon sizing.²³

Expansion Index and Embedment Depth as Imaging Endpoints

Embedment depth is a strut-level parameter, whereas the expansion index is a lesion-level parameter. Depending on the objective of the clinical study, either parameter could be used as an imaging endpoint. From the practical point of view, strut embedment assessment is only feasible when using offline dedicated software. For guidance in the catheter laboratory, the expansion index is more practical and feasible than the embedment depth assessment which requires off-line dedicated software.

Study Strengths and Limitations

The relationship between implantation technique and strut embedment of the Absorb BVS was evaluated with highly reproducible, solid methodology in a clinical subset for the first time.⁹ However, some limitations need to be acknowledged for the current study. First, the implantation technique at both pre- and postdilatation, including balloon type and pressure, was decided by the operators. Some of the paradoxical results could stem from the non-randomized nature of the present post hoc analysis. Second, lack of pre-implantation OCT did not allow us to assess the commonly used parameters of scaffold performance (eg, acute lumen gain). Third, as described before, the balloon inflation time and number of balloon inflations could not be analyzed. In addition, although the effect of balloon pressure on strut embedment was not clearly demonstrated in the present study, ultra-high-pressure balloon inflation possibly influences strut embedment. Fourth, although no additional increase in dissection was observed in lesions treated with the most aggressive technique in the current population, the safety of such techniques is still unclear. Moreover, severely calcified lesions that were not expandable with balloons were excluded by the trial’s protocol. Therefore, the results and conclusions of the present study cannot be applied directly to such complex lesions. With the absence of a prespecified method, the current study could not conclude on the optimal implantation technique for the Absorb BVS. Fifth, OCT assessment was performed using 3 different systems, which could affect measurement of a subtle OCT parameter such as embedment depth. Lastly, the OCT assessment was performed after implantation of the scaffolds, which would influence the reference vessel assessment. It would be difficult to directly translate our results into a prescaffold implantation sizing process. The post hoc nature of the present study limits the result to hypothesis generation. A prospective randomized controlled trial in which OCT parameters are the major endpoints is warranted to determine the optimal implantation technique for Absorb BVS.

Conclusions

The mean embedment ratio of the Absorb struts was approximately 40%. Underlying plaque morphology had a strong effect on strut embedment, whereas implantation technique appeared not to have a direct effect on strut embedment. Expansion index correlated with the size of the pre- and postdilatation balloons. A predilatation balloon equal to or slightly smaller than the OCT-derived RVD, as well as a slightly oversized postdilation balloon (≥0.25 mm larger than the OCT-derived RVD), seems to be reasonable in order to achieve sufficient expansion. Further prospective trials are warranted to evaluate the safety and efficacy of this proposed implantation technique.

Conflict of Interest

Y.S. is a consultant of GOODMAN and has received a grant from Fukuda Memorial Foundation for Medical Research and SUNRISE lab. Y.O. and P.W.S. are members of the Advisory Board for Abbott Vascular. J.J.P. receives institutional grants from Abbott Vascular, Boston Scientific, and Medtronic, and is a member of the Medical Advisory Board of Boston Scientific. K.T. is a member of the Advisory Board for Abbott Vascular Japan and receives honorarium for lectures. T.K. is a member of the Advisory Board for Abbott Vascular and receives a research grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Funding

The ABSORB Japan study was funded by Abbott Vascular, Santa Clara, CA, USA.

References

• 1.    Kimura  T,  Kozuma  K,  Tanabe  K,  Nakamura  S,  Yamane  M,  Muramatsu  T, et al. A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan. Eur Heart J 2015; 36: 3332–3342.
• 2.    Gao  R,  Yang  Y,  Han  Y,  Huo  Y,  Chen  J,  Yu  B, et al. Bioresorbable vascular scaffolds versus metallic stents in patients with coronary artery disease: ABSORB China Trial. J Am Coll Cardiol 2015; 66: 2298–2309.
• 3.    Ellis  SG,  Kereiakes  DJ,  Metzger  DC,  Caputo  RP,  Rizik  DG,  Teirstein  PS, et al. Everolimus-eluting bioresorbable scaffolds for coronary artery disease. N Engl J Med 2015; 373: 1905–1915.
• 4.    Serruys  PW,  Chevalier  B,  Dudek  D,  Cequier  A,  Carrie  D,  Iniguez  A, et al. A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): An interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial. Lancet 2015; 385: 43–54.
• 5.    Ishibashi  Y,  Nakatani  S,  Sotomi  Y,  Suwannasom  P,  Grundeken  MJ,  Garcia-Garcia  HM, et al. Relation between bioresorbable scaffold sizing using QCA-Dmax and clinical outcomes at 1 year in 1,232 patients from 3 study cohorts (ABSORB Cohort B, ABSORB EXTEND, and ABSORB II). JACC Cardiovasc Interv 2015; 8: 1715–1726.
• 6.    Sotomi  Y,  Ishibashi  Y,  Suwannasom  P,  Nakatani  S,  Cho  YK,  Grundeken  MJ, et al. Acute gain in minimal lumen area following implantation of everolimus-eluting ABSORB biodegradable vascular scaffolds or Xience metallic stents: Intravascular ultrasound assessment from the ABSORB II Trial. JACC Cardiovasc Interv 2016; 9: 1216–1227.
• 7.    Sotomi  Y,  Suwannasom  P,  Tenekecioglu  E,  Tateishi  H,  Abdelghani  M,  Serruys  PW, et al. Differential aspects between cobalt-chromium everolimus drug-eluting stent and Absorb everolimus bioresorbable vascular scaffold: From bench to clinical use. Expert Rev Cardiovasc Ther 2015; 13: 1127–1145.
• 8.    Serruys  PW,  Suwannasom  P,  Nakatani  S,  Onuma  Y. Snowshoe versus ice skate for scaffolding of disrupted vessel wall. JACC Cardiovasc Interv 2015; 8: 910–913.
• 9.    Sotomi  Y,  Tateishi  H,  Suwannasom  P,  Dijkstra  J,  Eggermont  J,  Liu  S, et al. Quantitative assessment of the stent/scaffold strut embedment analysis by optical coherence tomography. Int J Cardiovasc Imaging 2016; 32: 871–883.
• 10.    de Jaegere  P,  Mudra  H,  Figulla  H,  Almagor  Y,  Doucet  S,  Penn  I, et al. Intravascular ultrasound-guided optimized stent deployment: Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study). Eur Heart J 1998; 19: 1214–1223.
• 11.    Suwannasom  P,  Sotomi  Y,  Ishibashi  Y,  Cavalcante  R,  Albuquerque  FN,  Macaya  C, et al. The impact of post-procedural asymmetry, expansion, and eccentricity of bioresorbable everolimus-eluting scaffold and metallic everolimus-eluting stent on clinical outcomes in the ABSORB II Trial. JACC Cardiovasc Interv 2016; 9: 1231–1242.
• 12.    Sotomi  Y,  Onuma  Y,  Suwannasom  P,  Tateishi  H,  Tenekecioglu  E,  Zeng  Y, et al. Is quantitative coronary angiography reliable in assessing the lumen gain after treatment with the everolimus eluting bioresorbable polylactide scaffold? EuroIntervention 2016 (in press).
• 13.    Tearney  GJ,  Regar  E,  Akasaka  T,  Adriaenssens  T,  Barlis  P,  Bezerra  HG, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: A report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol 2012; 59: 1058–1072.
• 14.    Brown  AJ,  Obaid  DR,  Costopoulos  C,  Parker  RA,  Calvert  PA,  Teng  Z, et al. Direct comparison of virtual-histology intravascular ultrasound and optical coherence tomography imaging for identification of thin-cap fibroatheroma. Circ Cardiovasc Imaging 2015; 8: e003487, doi:10.1161/CIRCIMAGING.115.003487.
• 15.    Puricel  S,  Cuculi  F,  Weissner  M,  Schmermund  A,  Jamshidi  P,  Nyffenegger  T, et al. Bioresorbable coronary scaffold thrombosis: Multicenter comprehensive analysis of clinical presentation, mechanisms, and predictors. J Am Coll Cardiol 2016; 67: 921–931.
• 16.    Sadamatsu  K,  Yoshida  K,  Yoshidomi  Y,  Koga  Y,  Amari  K,  Tokunou  T. Comparison of pre-dilation with a non-compliant balloon versus a dual wire scoring balloon for coronary stenting. World J Cardiovasc Dis 2013; 3: 395–400.
• 17.    Dirschinger  J,  Kastrati  A,  Neumann  FJ,  Boekstegers  P,  Elezi  S,  Mehilli  J, et al. Influence of balloon pressure during stent placement in native coronary arteries on early and late angiographic and clinical outcome: A randomized evaluation of high-pressure inflation. Circulation 1999; 100: 918–923.
• 18.    Hovasse  T,  Mylotte  D,  Garot  P,  Salvatella  N,  Morice  MC,  Chevalier  B, et al. Duration of balloon inflation for optimal stent deployment: Five seconds is not enough. Catheter Cardiovasc Interv 2013; 81: 446–453.
• 19.    Iwamoto  Y,  Okamoto  M,  Hashimoto  M,  Fukuda  Y,  Iwamoto  A,  Iwasaki  T, et al. Better stent expansion by two-time inflation of stent balloon and its responsible mechanism. J Cardiol 2012; 59: 160–166.
• 20.    Kitahara  H,  Waseda  K,  Yamada  R,  Otagiri  K,  Tanaka  S,  Kobayashi  Y, et al. Acute stent recoil and optimal balloon inflation strategy: An experimental study using real-time optical coherence tomography. EuroIntervention 2016; 12: e190–e198, doi:10.4244/EIJV12I2A32.
• 21.    Gutierrez-Chico  JL,  Serruys  PW,  Girasis  C,  Garg  S,  Onuma  Y,  Brugaletta  S, et al. Quantitative multi-modality imaging analysis of a fully bioresorbable stent: A head-to-head comparison between QCA, IVUS and OCT. Int J Cardiovasc Imaging 2012; 28: 467–478.
• 22.    Kubo  T,  Akasaka  T,  Shite  J,  Suzuki  T,  Uemura  S,  Yu  B, et al. OCT compared with IVUS in a coronary lesion assessment: The OPUS-CLASS study. JACC Cardiovasc Imaging 2013; 6: 1095–1104.
• 23.    Mattesini  A,  Secco  GG,  Dall’Ara  G,  Ghione  M,  Rama-Merchan  JC,  Lupi  A, et al. ABSORB biodegradable stents versus second-generation metal stents: A comparison study of 100 complex lesions treated under OCT guidance. JACC Cardiovasc Interv 2014; 7: 741–750.
• 24.    Onuma  Y,  Serruys  PW,  Muramatsu  T,  Nakatani  S,  van Geuns  RJ,  de Bruyne  B, et al. Incidence and imaging outcomes of acute scaffold disruption and late structural discontinuity after implantation of the absorb Everolimus-Eluting fully bioresorbable vascular scaffold: Optical coherence tomography assessment in the ABSORB cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions). JACC Cardiovasc Interv 2014; 7: 1400–1411.
• 25.    Tateishi  H,  Suwannasom  P,  Sotomi  Y,  Nakatani  S,  Ishibashi  Y,  Tenekecioglu  E, et al. Edge Vascular response after resorption of the everolimus-eluting bioresorbable vascular scaffold: A 5-year serial optical coherence tomography study. Circ J 2016; 80: 1131–1141.
• 26.    Jimenez  JM,  Davies  PF. Hemodynamically driven stent strut design. Ann Biomed Eng 2009; 37: 1483–1494.
• 27.    Windecker  S,  Kolh  P,  Alfonso  F,  Collet  JP,  Cremer  J,  Falk  V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization. EuroIntervention 2015; 10: 1024–1094.
• 28.    Sotomi  Y,  Shlofmitz  RA,  Colombo  A,  Serruys  PW,  Onuma  Y. Patient selection and procedural considerations for coronary orbital atherectomy system. Interv Cardiol Rev 2016; 11: 33–38.