Author + information
- Received July 19, 2017
- Revision received November 26, 2017
- Accepted November 28, 2017
- Published online April 2, 2018.
- Kozo Okada, MDa,
- Yasuhiro Honda, MDa,∗ (, )
- Hideki Kitahara, MDa,
- Kyuhachi Otagiri, MDa,
- Shigemitsu Tanaka, MDa,
- M. Brooke Hollak, RNa,
- Paul G. Yock, MDa,
- Jeffrey J. Popma, MDb,
- Hajime Kusano, PhDc,
- Wai-Fung Cheong, PhDc,
- Krishnankutty Sudhir, MD, PhDa,c,
- Peter J. Fitzgerald, MD, PhDa,
- Takeshi Kimura, MDd,
- on behalf of the ABSORB Japan Investigators
- aDivision of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California
- bDepartment of Internal Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- cClinical Science and Medical Affairs, Abbott Vascular, Santa Clara, California
- dDepartment of Cardiovascular Medicine, Kyoto University Hospital, Kyoto, Japan
- ↵∗Address for correspondence:
Dr. Yasuhiro Honda, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Room H3554, Stanford, California 94305-5637.
Objectives The aim of this study was to characterize post-procedural intravascular ultrasound (IVUS) findings in the ABSORB Japan trial, specifically stratified by the size of target coronary arteries.
Background Despite overall noninferiority confirmed in recent randomized trials comparing bioresorbable vascular scaffolds (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting metallic stents (CoCr-EES), higher event rates of Absorb BVS have been reported with suboptimal deployment, especially in small coronary arteries.
Methods In the ABSORB Japan trial, 150 patients (2:1 randomization) were scheduled in the IVUS cohort. Small vessel was defined as mean reference lumen diameter <2.75 mm. Tapered-vessel lesions were defined as tapering index (proximal/distal reference lumen diameter) ≥1.2.
Results Overall, IVUS revealed that the Absorb BVS arm had smaller device expansion than the CoCr-EES arm did, which was particularly prominent in small- and tapered-vessel lesions. Higher tapering index was also associated with higher rates of incomplete strut apposition in Absorb BVS, but not in CoCr-EES. With respect to procedural techniques, small-vessel lesions were treated more frequently with noncompliant balloons at post-dilatation but using significantly lower pressure in the Absorb BVS arm. In contrast, tapered-vessel lesions were post-dilated at equivalent pressure but with significantly smaller balloon catheters in the Absorb BVS arm, compared with the CoCr-EES arm.
Conclusions The significantly smaller device expansion especially in small vessels may account for the poorer outcomes of Absorb BVS in this lesion type. Appropriate optimization strategy, possibly different between polymeric and metallic devices, needs to be established for bioresorbable scaffold technology. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 Absorb™ BVS) in Japanese Population [ABSORB JAPAN]; NCT01844284)
Recent randomized controlled trials have shown equivalent safety and efficacy outcomes at the midterm between everolimus-eluting bioresorbable vascular scaffold (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting stent (CoCr-EES) (both Abbott Vascular, Santa Clara, California) (1–4). However, a higher rate of scaffold thrombosis and its association with inadequate scaffold expansion have been reported in multicenter observational studies and recent meta-analyses (5–8). Previous studies have also reported that post-procedural nonuniform scaffold expansion, device-vessel mismatch, and the use of Absorb BVS in small vessels were associated with adverse clinical events (2,9,10). These data suggest that knowledge of acute device performance and deployment characteristics may be important to ensure favorable clinical outcomes and reduce adverse events.
The ABSORB Japan (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [AbsorbTM BVS] in Japanese Population) trial was a randomized, controlled trial comparing the Absorb BVS with the control CoCr-EES, designed to support regulatory approval of the Absorb BVS in Japan. It included an intravascular ultrasound (IVUS) cohort study (1), providing a unique opportunity to compare the acute results of polymeric scaffold and metallic stent implantation. In addition, there may be potential differences in angiographic measures between thicker radiolucent polymeric scaffold and thinner, more radiodense metallic stents. Therefore, the primary aim of this study was to systematically characterize post-procedural IVUS findings in the ABSORB Japan trial, focusing especially on acute device performance related to procedural factors and lesion characteristics. Additionally, the secondary aim was to compare differences between quantitative coronary angiography (QCA) and IVUS measurements, understanding of which is considered essential for image-guided BVS implantation and post-deployment optimization.
The design of the ABSORB Japan trial has been described previously (1). In brief, the ABSORB Japan trial was a prospective, multicenter, randomized, single-blind, active-controlled clinical trial in which 400 patients undergoing percutaneous coronary intervention from 38 investigational sites in Japan were randomized in a 2:1 ratio to treatment with Absorb BVS or the XIENCE CoCr-EES. Among the study cohorts, 150 patients were scheduled in the IVUS cohort. The Institutional Review Board at each investigational site approved the clinical trial protocol. All patients provided written informed consent before enrollment.
Patients were eligible for enrollment if they were ≥20 years of age and had evidence of myocardial ischemia (stable angina, unstable angina, or silent ischemia). Patients with left ventricular ejection fraction <30%, estimated glomerular filtration rate <30 ml/min/1.73 m2, recent myocardial infarction, and those at high bleeding risk were excluded. Key angiographic inclusion criteria were lesions with no more than 24 mm in length, reference lumen diameter (RLD) of ≥2.5 to ≤3.75 mm, and diameter stenosis (DS) of ≥50 to <100% on visual assessment. Key angiographic exclusion criteria were left main or ostial location; excessive vessel tortuosity; heavy calcification proximal to or within the target lesion; restenotic lesion; and bifurcation lesion with side branch ≥2 mm in diameter, requiring protection guidewire or dilation.
The study allowed treatment of up to 2 de novo lesions in separate epicardial coronary arteries. Successful pre-dilation of the target lesion was mandatory. Device sizes available in the study were: 2.5, 3.0, and 3.5 mm in diameter and 8, 12, 18, and 28 mm in length. The target lesion had to be treated with a single study device and planned overlapping was not allowed. Post-dilatation of Absorb BVS was not mandatory but was allowed, using a low-profile, high-pressure, noncompliant balloon with diameter ≤0.5 mm larger than the nominal size. Post-dilatation of CoCr-EES was per standard of care.
Quantitative coronary angiography
QCA was performed at baseline and post-procedure, using MEDIS QAngio XA 7.3 (Medis Medical Imaging Systems, Leiden, the Netherlands) at Beth Israel Deaconess Medical Center. Quantitative measurements included lesion length; minimum lumen diameter (MLD); proximal, distal, and mean (average of proximal and distal) RLD; DS; acute gain (in-device MLD at post-procedure minus MLD at baseline); and tapering index (proximal/distal RLD). MLD and RLD were obtained by the average values of 2 different projections. Smaller MLD was used for comparison with IVUS-determined MLD at minimum lumen area (MLA) site. Procedure success was defined as residual in-device DS ≤30%. Device sizing was evaluated by nominal device diameter minus mean RLD and classified as undersized (≤−0.25 mm), properly sized (−0.25 to 0.25 mm), and oversized (>0.25 mm), respectively. Very small vessels were defined as vessels with mean RLD <2.25 mm (2). Angulated lesions were defined as lesions with bend angle ≥30°. To compare mean RLD with mean reference lumen and vessel diameters by IVUS, mean RLD was divided into 4 subgroups (<2.50, 2.50 to 3.00, 3.00 to 3.50, and >3.50 mm).
IVUS was performed in a standard manner using an automated transducer pullback at 0.5 mm/s with a commercially available imaging system (40-MHz IVUS [Boston Scientific Corporation, Marlborough, Massachusetts or Terumo Corporation, Kanagawa, Japan]; 45-MHz or 20-MHz IVUS [Volcano Corporation, San Diego, California]). IVUS-guided PCI was not recommended by the study protocol, but operators were allowed to use IVUS information to optimize device deployment. Final IVUS images obtained at the end of procedure were submitted for independent IVUS analysis at Stanford Cardiovascular Core Analysis Laboratory, blinded to clinical and angiographic information. Using a validated quantitative IVUS analysis system (echoPlaque, Indec Systems, Santa Clara, California), vessel, lumen, device (scaffold or stent), and peridevice plaque (vessel minus device) areas were manually traced at the leading edge of boundaries at 1-mm intervals from proximal to distal 5-mm reference segments throughout the target segment with automated interpolated measurements of the remaining frames. Each volume calculated using Simpson’s method was standardized as volume index (volume/analyzed length [mm3/mm]). In the present study, acute device performance was evaluated by 3 indexes: 1) percent device expansion was calculated as a ratio of device volume index (percent volume expansion) or minimum device area (percent area expansion) to reference lumen volume index (average of proximal and distal references); 2) uniformity index of device expansion (minimum device area/maximum device area) and coefficient of variation of device cross-sectional areas (SD of device area/mean device area) were evaluated as indexes of uniform expansion; and 3) incomplete strut apposition (ISA) was defined as separation of at least 1 strut from the intimal surface, with evidence of blood flow behind the strut(s) in a vessel segment not associated with any side branches. Similar to QCA analysis, device sizing was also evaluated and classified by nominal device diameter minus mean RLD. Small-vessel lesions were defined as lesions with mean RLD <2.75 mm, which corresponded to mean RLD by QCA <2.5 mm (key exclusion criteria) in this population (Figure 1). Tapered-vessel lesions were defined as tapering index (proximal/distal RLD) ≥1.2. Maximum, minimum, and average lumen diameters at MLA site were also measured, and lumen eccentricity at MLA site was calculated as (maximum lumen diameter minus MLD)/maximum lumen dimeter.
Sample size calculation for the IVUS cohort of ABSORB Japan trial was performed to assess the in-device mean lumen area change from post-procedure to 3 years as the secondary-powered endpoint of the trial. Statistical calculations were performed with JMP 10 software (SAS Institute Inc., Cary, North Carolina). Data are expressed as frequencies and percentages for categorical variables and as mean ± SD for continuous variables. Categorical comparisons were performed using chi-square test or Fisher exact test. Continuous values were compared using unpaired or paired Student t test, Wilcoxon rank sum test, nonparametric Mann-Whitney U test, or 1-way analysis of variance, as appropriate. Correlations between continuous variables were investigated using linear regression analysis. Logistic regression analysis was performed to find the relationship of the presence of ISA to the following factors: proximal lesions, calcified lesions, tortuous lesions, angulated lesions, eccentric lesions, lesion type B2/C, and IVUS indexes (mean reference lumen diameter, tapering index, and device volume expansion). A p value <0.05 was considered statistically significant.
Patient, lesion, and procedural characteristics
Between April 2013 and January 2014, 154 lesions from 149 patients were officially enrolled in this IVUS cohort of the ABSORB Japan trial (Figure 2). One lesion was assigned to Absorb BVS but received CoCr-EES because the Absorb BVS could not be delivered in the target lesion. Ten lesions were excluded from quantitative analysis because of overlapping of 2 different devices, missing IVUS images, inconsistent pullback (qualitative assessment was still available in 2 lesions), or partial scanning of the device segment. As a result, quantitative analysis included 144 lesions; qualitative analysis included 146 lesions.
Baseline patient and lesion characteristics were comparable between the 2 device arms, except for a tendency toward lower prevalence of prior myocardial infarction in the Absorb BVS arm (Table 1). Overall, patient age was 67 ± 9 years, and diabetes was present in 28.4% of the patients. Stable coronary artery disease was present in 87.2% of the patients and 96.5% of the patients had treatment of 1 study target lesion only.
No statistically significant difference was seen in procedural characteristics between the 2 device arms (Table 2). Pre-dilation was performed using slightly undersized balloons with moderate pressure in both arms. Total device length was similar between the arms, whereas nominal device diameter and device-deployment pressure tended to be smaller in the Absorb BVS arm compared with the CoCr-EES arm. Post-dilation was performed in a similar proportion, whereas there was a tendency toward greater use of noncompliant balloons in the Absorb BVS arm. Nominal post-balloon diameter and dilation pressure did not differ significantly between the arms.
At baseline, QCA indexes were comparable in the 2 device arms (Table 3). Also, the percentage of very small vessels, tapering index, and device sizing did not differ significantly between the arms. At post-procedure, the Absorb BVS arm showed significantly smaller MLD and acute gain with greater residual DS, compared with the CoCr-EES arm at in-device segments, whereas these indexes did not differ significantly between the arms at in-segments. Overall, higher tapering index significantly correlated with smaller in-device MLD (r = −0.21, p = 0.012), which was also observed within the Absorb BVS arm (r = −0.24, p = 0.017). In contrast, this relationship was not seen within the CoCr-EES arm (r = −0.11, p = 0.48).
Post-procedural IVUS results are summarized in Table 4. At reference segments, IVUS indexes were similar between the 2 device arms. No significant residual dissection was seen at reference segments in either arm. Target lesion length, vessel and peri-device volumes, and device sizing were also comparable between the arms. In contrast, at in-device segments, lumen and device volumes, minimum lumen and device areas, and MLD at MLA site were significantly smaller in the Absorb BVS arm than in the CoCr-EES arm. The Absorb BVS also showed more nonuniform expansion (i.e., smaller uniformity index, greater coefficient of variation of device areas, and greater lumen eccentricity at MLA site) compared with the CoCr-EES. On the other hand, the incidence of prolapse was lower in the Absorb BVS arm compared with the CoCr-EES arm.
Percent device expansion in relation to the reference segment dimension was analyzed in 117 lesions because neither proximal nor distal reference was available due to the involvement of major branches (including ostial lesions) in 27 lesions. Overall, smaller percent volume expansion was seen in the Absorb BVS arm compared with the CoCr-EES arm, which was particularly prominent in small-vessel lesions (Figure 3). Similar results were also seen in percent area expansion. On the other hand, greater nonuniform expansion in the Absorb BVS was observed regardless of vessel size (Figure 4).
Tapered-vessel lesions were seen in a similar proportion in small- and large-vessel lesions (26.1% vs. 23.9%; p = 0.79). In the Absorb BVS arm, higher tapering index tended to correlate with smaller device expansion (device volume, minimum device area, and percent expansion), which was not observed in the CoCr-EES arm (Table 5). As a result, smaller device volume and percent volume expansion, seen in the Absorb BVS arm compared with the CoCr-EES arm, were more prominent in tapered-vessel lesions (Figure 5). Combined together, the difference between the arms for device expansion was most accentuated in tapered lesions in small vessels (percent volume expansion: 0.89 ± 0.12% vs. 1.14 ± 0.17%; p = 0.02).
The overall incidence of ISA tended to be lower in the Absorb BVS arm compared with the CoCr-EES arm (Table 4). Among several lesion characteristics, only higher tapering index was associated with occurrence of ISA (logistic regression: p = 0.01) in the Absorb BVS arm, whereas this relationship was not observed in the CoCr-EES arm. Accordingly, in the Absorb BVS arm, lesions with ISA had a significantly higher tapering index than lesions without ISA (1.26 ± 0.19 vs. 1.11 ± 0.14; p = 0.009), whereas no difference was found in tapering index in the CoCr-EES arm (1.13 ± 0.15 vs. 1.11 ± 0.20; p = 0.85). On the other hand, lesion type (B2 or C) (p = 0.01), greater mean reference lumen area (p = 0.048) and smaller percent area expansion (p = 0.03) were associated with occurrence of ISA in the CoCr-EES arm.
Overall, procedure profiles did not differ significantly between the arms, except for several differences in pre-dilation and post-dilation strategies found in complex lesion subsets. Specifically, small-vessel lesions were treated more frequently with noncompliant balloons at post-dilatation but using significantly lower pressure in the Absorb BVS arm compared with the CoCr-EES arm (Table 6). In contrast, tapered-vessel lesions were post-dilated at equivalent pressure, but with significantly smaller balloons in the Absorb BVS arm than in the CoCr-EES arm (Table 7).
Comparison of IVUS and QCA
At reference segments, mean RLD at post-procedure by QCA was significantly smaller than mean RLD measured by IVUS (p < 0.0001) (Tables 3 and 4). The difference between the 2 modalities was −0.19 ± 0.26 mm (−0.84 to 0.43 mm), which did not differ significantly between the Absorb BVS and CoCr-EES arms (−0.20 ± 0.25 mm vs. −0.17 ± 0.28 mm; p = 0.64). Mean RLD at post-procedure by QCA positively correlated with both mean RLD and reference vessel diameter (RVD) by IVUS, but their scatter plots were relatively widespread because of various residual stenosis at reference segments (Figure 1). When the analyses were performed in the subgroups classified based on vessel size by QCA, mean RLD and RVD measured by IVUS were widely distributed in each subgroup (Figure 6). As a result, 20.8% of the “properly sized” devices by QCA were considered as “undersized” by IVUS. There was also positive correlation of tapering index between QCA and IVUS but its correlation coefficient was moderate (r = 0.65, p < 0.0001).
At in-device segments, smaller MLD by QCA was also significantly smaller than IVUS-determined MLD (p = 0.004). However, the percent difference in MLD between the 2 imaging modalities was not significantly different between the 2 device arms (Absorb BVS: 2.9 ± 13.2% vs. CoCr-EES: 3.2 ± 10.9%; p = 0.91). In contrast, the percent difference between MLD by QCA and IVUS-determined average lumen diameter at MLA site was significantly greater in the Absorb BVS arm compared with the CoCr-EES arm (8.9 ± 10.8% vs. 4.7 ± 9.3%; p = 0.02), likely attributable to greater lumen eccentricity in the Absorb BVS arm than in the CoCr-EES arm.
The main findings of this study are: 1) overall, the Absorb BVS arm showed smaller device expansion and greater nonuniformity of expansion compared with the CoCr-EES arm; 2) smaller device expansion seen in the Absorb BVS arm compared with the CoCr-EES arm was more prominent in complex lesion subsets, such as small-vessel lesions and tapered-vessels; 3) in these lesion subsets, operator’s post-dilation procedures were significantly different between the 2 devices, with respect to the use of noncompliant balloons, dilation pressures, and balloon diameters; 4) higher tapering index was associated with higher rates of ISA in the Absorb BVS arm, but not in the CoCr-EES arm; and 5) QCA underestimated both RLD and reference device diameter as compared with IVUS, but with no apparent device specific difference.
In the present study, the Absorb BVS arm had smaller device expansion compared with the CoCr-EES arm, which was more prominent in complex lesions. Possible explanation for this observation may involve several factors, including device-related and procedure-related differences between the polymeric scaffold and conventional metallic stents. A recent experimental study of metallic stents has revealed that both stent materials/designs and post-dilatation strategies can significantly impact initial stent expansion and subsequent acute recoil, thereby affecting final stent expansion (11). The Absorb BVS is similar in design to the CoCr-EES, but is made of a lactic acid-based polymer, which can result in even greater intrinsic differences in mechanical device properties. In fact, despite the similar radial strength reported in bench studies, the Absorb BVS can show greater acute recoil than metallic stents in vivo, particularly in complex lesions (12,13). With respect to operators’ device deployment and optimization strategy in the present study, whereas device sizing and initial deployment procedures were similar in the 2 device arms, significant differences were observed in post-deployment optimization, particularly in small or tapered-vessel lesions. The more conservative post-dilation strategy observed in the Absorb BVS arm appears attributable to early concern of scaffold disruption resulting in focal loss of mechanical support which can occur with overexpansion of the device beyond its expansion limit (14). However, as clinical experience has been accumulated since the start of this trial, it has been learned that the scaffold disruption could be avoided if the post-dilation balloon is not sized >0.5 mm (nominal expansion limit of BVS) larger than the nominal BVS diameter, regardless of dilation pressure (15). Recent investigations have also demonstrated that appropriate balloon size and high-pressure post-dilation with noncompliant balloons are feasible and crucial for optimal BVS expansion (6,16–20). The present study supports this conclusion, whereas more detailed optimization strategies specific to the polymeric scaffold, if any (for instance, single long vs. multiple short inflations), are yet to be investigated.
The use of Absorb BVS in small vessels, particularly in vessels <2.25 mm, has been reported to be associated with an increased risk of scaffold thrombosis (2,6). Although reasons for this observation are likely multifactorial, combined with the results of a previous report (6), the present study suggests that inadequate scaffold expansion, more frequently occurring in small vessels than in larger vessels, may, in part, contribute to the higher risk of the adverse events in this lesion subset. As current Absorb BVS has relatively thick and wide struts, underexpansion of the scaffold leads to the crowding of multiple thick struts, which decreases the vessel lumen and results in a larger footprint, causing disruption of laminar flow and platelet activation due to high shear stress and ultimately promoting thrombotic events (21). Therefore, it may be important, especially for the treatment of small-vessel lesions, that the scaffold has to be fully post-dilated, thus embedding the struts deeply in the vessel wall to reduce the footprint and favoring rapid endothelialization. Additionally, meticulous lesion preparation, optimal vessel-device sizing (including avoiding very small vessels), and intravascular imaging guidance may also help reduce underexpansion and thereby improve the outcomes in small vessels (6,17).
The present study also demonstrated significantly greater nonuniform expansion in the Absorb BVS arm than in the CoCr-EES arm. To date, compared with minimum stent area or the degree of stent expansion, there has been less attention dedicated to uniformity of device expansion. In polymeric scaffolds, however, a recent study reported that nonuniform scaffold expansion was associated with adverse clinical events (9). Multiple investigations have also suggested that aggressive lesion preparation, in combination with a high pressure post-dilation, may contribute to achieving uniform scaffold expansion (9,19,20). The exact clinical significance of uniform expansion in BVS implantation, which may differ between polymeric and conventional metallic devices, may warrant further investigation.
Incomplete strut apposition
Despite smaller device expansion, the Absorb BVS arm tended to show lower rates of ISA compared with the CoCr-EES arm, both in complex and noncomplex lesions. There may be 2 possible explanations for this observation. First, despite the lower tensile properties mentioned previously, polymeric scaffolds may have greater conformability and flexibility compared with metallic stents (22), which may contribute to good strut apposition. Second, the image resolution of IVUS can affect accurate detection of ISA. Compared with optical coherence tomography (OCT), IVUS is technically limited in detailed strut assessment, which appears to be accentuated in the evaluation of polymeric scaffolds due to greater image artifacts caused by polymeric struts than by conventional metallic struts (i.e., larger blooming effects, significant side-lobe artifacts, and strong ultrasound spokes behind the struts), potentially leading to lower detection of ISA in the Absorb BVS arm. Of note, although the definitive answer would require combined use of IVUS and OCT in the same patient population, the OCT cohort of this trial also reported lower rates of ISA in the Absorb BVS arm, indirectly suggesting the first hypothesis mentioned previously as the leading explanation for the current finding (23).
Interestingly, higher tapering index was associated with higher ISA rates in the Absorb BVS arm but not in the CoCr-EES arm, which may be explained by smaller balloon diameters for post-dilation used in the Absorb BVS arm for the treatment of tapered-vessel lesions. The current Absorb BVS comes in 3 sizes and can only be expanded up to 0.5 mm over the nominal device size, beyond which there is an increasing risk of device disruption. Thus, accurate vessel sizing is considered important to avoid significant device-vessel mismatch, select the proper size of post-dilation balloon, and reduce the ISA rates particularly in tapered-vessel lesions. Sequential implantation of scaffolds with different diameters may also help to accommodate different vessel diameters in this lesion subset. Of note, similar to the uniformity of device expansion discussed previously, clinical relevance of post-procedure ISA in bioresorbable scaffolds can be different from what we have learned from metallic platforms. In addition, it remains to be investigated whether different device-sizing strategies need to be established for Absorb BVS (e.g., on the basis of the proximal reference, rather than the average of the proximal and distal references, in tapered-vessel lesions).
IVUS versus QCA
Accurate vessel size assessment is essential for appropriate device sizing of Absorb BVS. Compared with visual estimation, QCA generally provides more objective lumen diameters but with no information on the true vessel size, particularly when reference vessel segments are also diseased. In contrast, intravascular imaging can offer detailed morphometry of both reference and lesion segments for determining exact vessel diameter and lesion length (18). Indeed, as compared with IVUS, mean RLDs were underestimated by QCA by up to −0.84 mm in the present study, and 20.8% of the “properly sized” devices by QCA were considered as “undersized” by IVUS. In addition, nearly one-half of proximal references and one-third of distal references had significant residual plaque burden (plaque volume >50%) uncovered by the device.
Theoretical concerns have also existed for the QCA assessment of in-device diameters within scaffold segments, because of possibly different angiographic projections between polymeric scaffolds and conventional metallic stents. Specifically, the thicker radiolucent struts of Absorb BVS, compared with the thinner, more radiodense struts of CoCr-EES, may cause weakening of vessel-contour contrast in angiography, which may lead to the discrepancy that in-device MLD misleadingly appears smaller despite adequate scaffold expansion. In the present study, however, QCA and IVUS showed no device-specific discrepancy in in-device MLD, with slight but statistically significant underestimation by QCA regardless of the device type. On the other hand, when comparing QCA-determined MLD with IVUS-determined average lumen diameter at MLA site, a significantly larger discrepancy was observed in Absorb BVS than in CoCr-EES, presumably due to greater nonuniform (or eccentric) expansion of Absorb BVS. Although intravascular imaging has clear advantages for precise reference, lesion, and device assessments to achieve optimal acute results, further studies are warranted to investigate if intravascular imaging guidance would be advisable to ultimately improve long-term clinical outcomes of fully bioresorbable scaffold technologies.
First, the IVUS cohort of the ABSORB Japan trial was not designed for detailed analyses of specific lesion subsets; therefore, the clinical impact of our findings needs to be determined in larger studies. Second, the sample size of the IVUS cohort was pre-determined to test the secondary powered endpoint of the original trial (i.e., serial lumen area change from post-procedure to 3 years), although most of the observed differences between the 2 device arms in small and tapered vessels reached statistical significance despite the limited sample sizes in the subanalyses of the current study. Third, the ABSORB Japan trial enrolled a selected patient population with primarily stable coronary artery disease and single de novo relatively simple target lesions. Thus, the study results may not be generalizable to truly complex lesions or patients with acute coronary syndromes. Fourth, because pre-interventional IVUS was not mandated by the protocol, influence of underlying plaque types on scaffold expansion could not be evaluated in detail. Last, for device area measurements, image resolution of the current IVUS technology primarily allows assessment of internal device dimensions. Although it offers comparative methodology for the assessment of BVS versus metallic stents, it remains to be clarified in subsequent OCT studies whether additional evaluation of external device dimensions as well as the effective flow area within lumen could provide incremental benefits to BVS research or clinical guidance.
In the ABSORB Japan trial, smaller device expansion seen in the Absorb BVS arm compared with the CoCr-EES arm was more prominent in small-vessel lesions, which may account for the poorer outcomes of Absorb BVS in this lesion type. In addition, significant vessel tapering appears to affect the strut apposition of Absorb BVS. Appropriate deployment and optimization strategies, possibly different between polymer and metallic devices, need to be established for bioresorbable scaffold technology, especially for the treatment of complex lesions.
WHAT IS KNOWN? A higher rate of scaffold thrombosis and its association with inadequate scaffold expansion have been reported in multicenter observational studies and recent meta-analyses.
WHAT IS NEW? Smaller device expansion seen in the Absorb BVS arm than in the CoCr-EES arm was more prominent in small-vessel lesions, which may be partially explained by relatively conservative post-dilation strategies in the Absorb BVS arm.
WHAT IS NEXT? Further studies will need to confirm the clinical relevance of our IVUS findings and whether intravascular imaging guidance will improve acute device performance and long-term outcomes of Absorb BVS.
The authors appreciate Heidi N. Bonneau, RN, MS, CCA, for her editorial review of the manuscript.
The ABSORB Japan trial was funded by Abbott Vascular, Santa Clara, California. Drs. Yock, Fitzgerald, and Kimura have received institutional research grant support from Abbott Vascular. Drs. Kusano, Cheong, and Sudhir are employees of Abbott Vascular. Dr. Popma has received institutional grant support from Boston Scientific, Medtronic, and Abbott Vascular; and has served on the advisory board for Boston Scientific and Abbott Vascular. Dr. Kimura has served on the advisory board for Abbott Vascular and Abbott Vascular Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- bioresorbable vascular scaffold
- cobalt-chromium everolimus-eluting stent(s)
- diameter stenosis
- incomplete strut apposition
- intravascular ultrasound
- minimum lumen area
- minimum lumen diameter
- optical coherence tomography
- quantitative coronary angiography
- reference lumen diameter
- reference vessel diameter
- Received July 19, 2017.
- Revision received November 26, 2017.
- Accepted November 28, 2017.
- 2018 American College of Cardiology Foundation
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