Abstract. Background. Previous randomized controlled trials demonstrated a higher rate of stent thrombosis with bioresorbable vascular scaffold (BVS) implantation as compared with second-generation drug-eluting stent in selected patients/lesions. However, long-term outcomes of BVS implantations that utilize an optimized technique (OIT) in unselected patients/lesions are lacking. The aim of this study was to assess the real-world, long-term clinical outcomes of BVS (Absorb; Abbott Vascular) with OIT. Methods and Results. In a cohort of 156 patients, a total of 347 BVS devices (435 lesions) were implanted, with intravascular ultrasound (IVUS) guidance utilized in 303 (87.3%) of the scaffolds. The primary efficacy endpoint was target-lesion revascularization (TLR) and the primary safety endpoint was scaffold thrombosis. Despite performing routine high-pressure postdilation, postintervention IVUS detected BVS underexpansion/malapposition in 53 scaffolds (28.7%), requiring further postdilation. At a median follow-up of 60 months (interquartile range, 45-73 months), TLR and scaffold thrombosis occurred in 16 patients (10.3%) and 1 patient (0.6%), respectively. At univariable analysis, IVUS-guided scaffold implantation was associated with lower TLR (odds ratio, 0.24; 95% confidence interval, 0.09-0.62; P<.01). Conclusion. The use of first-generation BVS with OIT in real-world patients/lesions was associated with acceptable long-term outcomes.
J INVASIVE CARDIOL 2021;33(2):E115-E122. Epub 2021 January 14.
Key words: bioresorbable scaffold, intravascular ultrasound, multivessel disease, stable angina
The bioresorbable vascular scaffold (BVS), a poly(L-lactide), naturally dissolving intracoronary device, has been designed to overcome metallic drug-eluting stent (DES) limitations, mainly represented by the persistent risk of stent-related adverse events, reported even at long-term follow-up. In addition, the presence of a temporary scaffold, coupled with restoration of physiological vasomotor function, offered an attractive potential for a more complete anatomical and functional vessel recovery.1
However, several randomized trials showed that BVS implantation in comparison with DES was associated with a reduced acute luminal gain, a smaller minimum luminal diameter, and a greater rate of residual stenosis with higher scaffold thrombosis.2 Indeed, BVS devices have thicker struts, less radial force, and more recoil compared with metallic stents, which can impact stent thrombosis and restenosis.3 As proposed by recent studies,8-11 these limitations can partially be overcome by performing intravascular-imaging guided optimal scaffold implantation. In this study, we evaluate long-term outcomes following BVS implantations guided by intravascular imaging in real-world percutaneous coronary intervention (PCI).
The Columbus ABSORB registry is a prospective, single-center, Italian registry including 156 consecutive patients treated with BVS at the EMO GVM Centro Cuore Columbus in Milan, Italy between October 2012 and December 2015. Criteria for BVS implantation were: no contraindications for at least 1 year; dual-antiplatelet therapy (DAPT), and PCI in 2.5-4.0 mm vessels with optimal lesion preparation. Successfully recanalized chronic total occlusions, bifurcation lesions, calcific lesions, and ostial lesions were included. Most of the patients treated had stable angina due to the referral pattern at our institution.
Clinical evaluation was performed at 6 months, followed by annual functional (stress echocardiography or myocardial single photon emission tomography or ergometric test) or anatomical (coronary angiography or coronary computed tomography angiography) assessment. All recorded events were confirmed by an attending physician. Each patient included in the registry signed an informed consent for both procedure and data collection.
Endpoints. The primary efficacy endpoint was target-lesion revascularization (TLR), while the primary safety endpoint was definite/probable scaffold thrombosis. Scaffold thrombosis was defined according to the Academic Research Consortium criteria.4 Device-oriented composite endpoint (DOCE) including cardiac death, target-vessel revascularization (TVR), ischemia-driven TLR, and infarct-related TLR was also assessed.
Statistical analysis. Data are expressed as mean ± standard deviation, and categorical data as numbers and percentages. Comparisons of clinical, angiographic, and procedural characteristics were performed by means of the Student’s t-test or Wilcoxon rank-sum test (continuous variables), or χ² test (categorical), and on the basis of the distribution. Patients who were lost to follow-up were censored at their last known contact. Cumulative event rates were analyzed using the Kaplan-Meier method, and the rate differences among the groups were estimated using the log-rank test. The prognostic relevance of different variables regarding the prediction of TLR was estimated using univariable Cox regression analysis. All analyses were performed using SPSS software, version 20.0 (IBM Corporation) and all reported P-values are 2-sided. P-values <.05 were considered significant.
Implantation technique. The scaffold implantation technique has been previously described.5 In brief, lesion preparation with a semicompliant and/or non-compliant balloon (1:1 balloon-to-artery ratio) was routinely performed. Rotational atherectomy, scoring and cutting balloons, and super high-pressure balloons were considered as in clinical practice. Intravascular imaging with intravascular ultrasound (IVUS) and/or optical coherence tomography (OCT) was almost routinely utilized following pre- and postdilation. BVS devices were implanted according to the manufacturer’s instructions and postdilation with high-pressure, non-compliant balloons was routinely performed, using a balloon no larger than 0.5 mm of the implanted BVS. Angiography vs IVUS optimization (AVIO) criteria were used to guide the target scaffold area.6
The following quantitative coronary angiography (QCA) parameters were assessed: reference vessel diameter before (RVDpre) and after predilation (RVDpost), minimal luminal diameter before (MLDpre) and after predilation (MLDpost), final stent minimal luminal diameter (MLDstent), percentage of baseline angiographic stenosis, and minimal scaffold area. DAPT consisted of aspirin plus ticagrelor, prasugrel, or clopidogrel for at least 12 months.
Study population. During the study period, a total of 156 consecutive patients were treated with BVS implantation. Baseline clinical characteristics are reported in Table 1. Median age was 66 ± 10 years, 140 (89.7%) were males, 31 (19.9%) were diabetic, and 32 (20.5%) had chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2). A total of 153 patients (98.1%) presented with stable coronary artery disease, with only 3 patients (1.9%) having an acute coronary syndrome (ACS), including 2 ST-segment elevation myocardial infarction (STEMI) patients. In addition, 120 patients (77.0%) had multivessel disease (defined as at least 2 vessels with critical stenosis) and 18.6% of the lesions were longer than 20 mm; 8.3% of the lesions had moderate-to-severe calcification, involving bifurcations in 8% of cases. In-stent restenosis (ISR) was seen in 4.3% of cases, 1.6% were chronic total occlusions (CTOs), and 66.2% were B2/C lesions.
Procedural characteristics. Table 2 and Table 3 show procedural and angiographic characteristics. Predilation was performed in the vast majority of patients (95.7%), while rotational atherectomy, cutting balloons, and very-high pressure balloons were used in 10 patients (15.6%) for lesion preparation. A total of 435 lesions were treated with the implantation of 347 BVS devices (2.2 BVS/patient; mean diameter, 2.8 mm; mean length, 25.4 mm); in 53 patients, at least 1 additional drug-eluting stent was utilized (91 drug-eluting stents implanted). High-pressure postdilation (≥17 atm) was performed in all PCIs. Intravascular imaging was performed in 303 (87.3%) of the BVS implantations; in 112 cases (32.3%), imaging was performed before BVS implantation. Stent underexpansion or malapposition was detected in almost one-third (28.7%) of the intravascular imaging runs performed after routine high-pressure postdilation. Specifically, these findings occurred in 53 BVS implantations, and 36 then underwent additional high-pressure or postdilation with a larger balloon (IVUS-guided BVS optimization).
The management of lesions with suboptimal imaging results was left to operator discretion. Lesions that did not undergo further interventions, despite suboptimal imaging result, were considered at risk of complications, such as scaffold fracture; therefore, adjunctive postdilation was not performed.
Follow-up evaluation. Clinical follow-up was available in all patients. The median follow-up was 60 months (interquartile range [IQR], 45-73 months), with at least 3-year follow-up available in 87% of the patients. Functional/anatomical evaluation during follow-up was reported in most of the patients as follows: coronary angiography in 51 patients (32.7%), with median follow-up of 24 months (IQR, 12-48 months); coronary multislice computed tomography scans in 44 patients (28.2%), with median follow-up of 36 months (IQR, 24-60 months); and non-invasive functional ischemic testing in 69 patients (44.2%), with median follow-up of 36 months (IQR, 24-60 months).
Clinical outcomes. At a median follow-up of 60 months (IQR, 45-73 months), TLR rate was 10.3% and scaffold thrombosis occurred in 1 patient (0.6%), who presented with STEMI a few hours post BVS implantation. Sudden cardiac death occurred in 3 patients (1.9%); 1 patient experienced severe left ventricular dysfunction and refused implantable cardioverter defibrillator implantation, 1 patient had BVS restenosis treated with drug-eluting stent in a complex PCI 10 months prior to his death; and 1 patient had to undergo 2 subsequent complex PCIs with BVS and DES at 48 months and 4 months before his death, respectively. However, these events were not considered due to the scaffold thrombosis because of the presence of clinically reasonable explanations for cardiac sudden death. Moreover, they were also close to a complex PCI with DES implantation. The DOCE rate was 13.5% (Table 4). Kaplan-Meier curves showing the incidence of follow-up TLR are shown in Figure 1. Figure 2 shows follow-up within 3 years, while Figure 3 shows the outcomes after the third year. At univariable analysis, IVUS guidance (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.09-0.62; P<.01) and the relatively higher postdilation balloon size compared with BVS size (OR, 0.10; 95% CI, 0.00-0.44; P=.02) were both protective factors against TLR occurrence (Table 5). As shown in Figure 4, TLR occurred more frequently during the first 3 years. Most of the patients continued DAPT beyond 1 year, as represented in Figure 5.
The analyzed cohort included mainly patients with stable coronary artery disease and heterogeneous-type lesions. To the best of our knowledge, this is the first real-world study on BVS in an all-comer population including a high rate of complex lesions with a long-term follow-up. The main findings of this study are: (1) long-term results following implantation of a first-generation BVS in patients with a high rate of complex lesions are acceptable; (2) an optimized implantation technique is important to ensure successful outcomes; and (3) IVUS-guided procedures guarantee a more accurate BVS implantation, leading to a better outcome. The univariable analysis demonstrated a protective role of IVUS against TLR. Scaffold underexpansion and malapposition can be accurately assessed by intracoronary imaging. Finally, a long-term DAPT strategy could mitigate the stent-related complications.
Previous retrospective studies involving patients with similarly complex multivessel stable CAD demonstrated a high rate of adverse events at mid-term follow-up. However, in these studies, the rate of intracoronary imaging use was low and an optimal implantation technique was not systematically performed.7 In the present study, the TLR rate at a median follow-up of 60 months was comparable with data from second-generation DES registries.8,9 A recent meta-analysis showed a similar reduction in TLR after 3 years of follow-up in a high-risk population; nevertheless, the studies included did not treat complex lesions.10 Recently, Ielasi et al11 and Caixeta et al12 reported favorable long-term outcomes in patients treated with BVS utilizing an optimal implantation technique. Caixeta et al showed that the use of intravascular imaging was a protective factor against major adverse cardiovascular endpoints, but only a small number of patients underwent IVUS assessment.12
Several factors may account for the adverse outcomes following BVS implantation, ie, large discrepancies between the proximal and distal reference vessel,13 geographical miss,14 BVS underexpansion,15,16 BVS asymmetry and eccentricity,17,18 and scaffold discontinuity and malapposition.19
IVUS guidance. Due to the increased strut thickness of the BVS, standard coronary angiography is frequently insufficient to detect stent underexpansion20 and facilitate good embedding of the struts in the vessel wall. Recent studies suggested that intracoronary imaging may be a useful predictor of future events due to its ability to detect non-uniform BVS expansion after postdilation17,21 and residual plaque burden.17 However, the influence of IVUS guidance on further postdilations is unknown. Despite the routine use of high-pressure postdilation in IVUS-guided PCIs, stent underexpansion/malapposition was detected in 53 of the 185 lesions (28.6%). In 36 of these 53 cases (67.9%), further postdilation was performed. Given the low rate of events and the small number of patients, it is not possible to perform a specific statistical analysis to support the additional benefit of IVUS-guided postdilation. Of note, similar studies performed with DES did not find any benefit in the use of IVUS-guided postdilation.6 Nevertheless, the findings from metallic drug-eluting stent implantation cannot be extrapolated to first-generation BVS implantation. This issue is likely to be addressed in the forthcoming HOWTO-BRS trial (How To Optimally Implant BioResorbable Scaffold–Intravascular Imaging Versus Quantitative Coronary Angiography Guidance; NCT03175523), which will compare an image-guided implantation technique with standard quantitative coronary angiography assessment alone.
Our long-term follow-up demonstrates an early increase in TLR in the first 3 years, followed by a plateau in the following years when the scaffold reabsorption process is completed (Figures 2-5).22,23 Similar findings have been reported,10 and if confirmed in subsequent randomized trials, may have significant implications for clinical practice and long-term management of patients implanted with BVS. The fact that 70% of the patients were still on DAPT after 1 year of BVS implantation may be an additional protection against events. Encouragingly, the lack of major bleeding events, despite a liberal long-term DAPT strategy, could be related to the careful selection of appropriate patients.
An important strength of the study is the close follow-up of patients undergoing long-term morphological (coronary angiogram and coronary computed tomography) and functional (stress test) assessments.
Study limitations. This study has several limitations. First, the results of this study are from a single center, with a relatively small study population, and our findings should be interpreted in light of the common limitations of retrospective studies. Second, in our cohort, a greater proportion of patients were managed with a long-term DAPT strategy, which may partially explain the low rate of adverse events. Moreover, almost all of the patients had stable coronary artery disease, limiting the ability to extrapolate our findings to other clinical scenarios. Unfortunately, 24 patients (15.0%) had a relatively short follow-up, with a median time of 26 months (IQR, 19-40 months). In 6 of these 24 patients, we were able to check their vital statuses at the end of follow-up through the regional civil registry. At the end of the inclusion period, we contacted 5 of the 6 patients excluded per protocol in our analysis (due to <6 months of follow-up), and none reported adverse cardiac events.
Long-term clinical outcomes following implantation of first-generation BVS in stable patients with a high prevalence of complex lesions were acceptable when a consistent optimal implantation strategy was adopted. The systematic use of IVUS was a protective factor against adverse events.
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From the 1Cardio-Thoraco-Vascular Department, Division of Cardiology and Postgraduate School in Cardiovascular Sciences, University of Trieste, Trieste, Italy; 2Interventional Cardiology Unit, GVM Care and Research, Maria Cecilia Hospital, Cotignola, Ravenna, Italy; 3Cardiology Department, New Tokyo Hospital, Chiba, Japan; and 4Division of Cardiology, Montefiore Medical Center, New York, United States.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Final version accepted: June 1, 2020.
Address for correspondence: Francesco Giannini, MD, Interventional Cardiology Unit GVM Care and Research Maria Cecilia Hospital, Cotignola, Ravenna, Italy. Email: firstname.lastname@example.org