Yuki Ishibashi

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

BACKGROUND Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up. METHODS In a single-blind, multicentre, randomised trial, we enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience, Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. The co-primary endpoints of this study are vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) and difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years. Secondary endpoints were procedural performance assessed by quantitative angiography and intravascular ultrasound; composite clinical endpoints based on death, myocardial infarction, and coronary revascularisation; device and procedural success; and angina status assessed by the Seattle Angina Questionnaire and exercise testing at 6 and 12 months. Cumulative angina rate based on adverse event reporting was analysed post hoc. This trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the bioresorbable scaffold group (335 patients, 364 lesions) or the metallic stent group (166 patients, 182 lesions). Dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation were higher and larger in the metallic stent group, whereas the acute recoil post implantation was similar (0.19 mm for both, p=0.85). Acute lumen gain was lower for the bioresorbable scaffold by quantitative coronary angiography (1.15 mm vs 1.46 mm, p<0.0001) and quantitative intravascular ultrasound (2.85 mm(2)vs 3.60 mm(2), p<0.0001), resulting in a smaller lumen diameter or area post procedure. At 1 year, however, cumulative rates of first new or worsening angina from adverse event reporting were lower (72 patients [22%] in the bioresorbable scaffold group vs 50 [30%] in the metallic stent group, p=0.04), whereas performance during maximum exercise and angina status by SAQ were similar. The 1-year composite device orientated endpoint was similar between the bioresorbable scaffold and metallic stent groups (16 patients [5%] vs five patients [3%], p=0.35). Three patients in the bioresorbable scaffold group had definite or probable scaffold thromboses (one definite acute, one definite sub-acute, and one probable late), compared with no patients in the metallic stent group. There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively). INTERPRETATION The everolimus-eluting bioresorbable scaffold showed similar 1-year composite secondary clinical outcomes to the everolimus-eluting metallic stent. FUNDING Abbott Vascular.

Everolimus-eluting bioresorbable vascular scaffolds for treatment of patients presenting with ST-segment elevation myocardial infarction: BVS STEMI first study

AIMS We evaluated the feasibility and the acute performance of the everolimus-eluting bioresorbable vascular scaffolds (BVS) for the treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS The present investigation is a prospective, single-arm, single-centre study, reporting data after the BVS implantation in STEMI patients. Quantitative coronary angiography and optical coherence tomography (OCT) data were evaluated. Clinical outcomes are reported at the 30-day follow-up. The intent-to-treat population comprises a total of 49 patients. The procedural success was 97.9%. Pre-procedure TIMI-flow was 0 in 50.0% of the patients; after the BVS implantation, a TIMI-flow III was achieved in 91.7% of patients and the post-procedure percentage diameter stenosis was 14.7 ± 8.2%. No patients had angiographically visible residual thrombus at the end of the procedure. Optical coherence tomography analysis performed in 31 patients showed that the post-procedure mean lumen area was 8.02 ± 1.92 mm(2), minimum lumen area 5.95 ± 1.61 mm(2), mean incomplete scaffold apposition area 0.118 ± 0.162 mm(2), mean intraluminal defect area 0.013 ± 0.017 mm(2), and mean percentage malapposed struts per patient 2.80 ± 3.90%. Scaffolds with >5% malapposed struts were 7. At the 30-day follow-up, target-lesion failure rate was 0%. Non-target-vessel revascularization and target-vessel myocardial infarction (MI) were reported. A non-target-vessel non-Q-wave MI occurred. No cases of cardiac death or scaffold thrombosis were observed. CONCLUSION In the present series, the BVS implantation in patients presenting with acute MI appeared feasible, with high rate of final TIMI-flow III and good scaffold apposition. Larger studies are currently needed to confirm these preliminary data.

Lessons learned from acute and late scaffold failures in the ABSORB EXTEND trial

AIMS Bioresorbable scaffolds are increasingly used in patients with coronary artery disease undergoing percutaneous coronary interventions. ABSORB EXTEND is an ongoing study that will recruit 800 patients. This report evaluates acute and late scaffold failure in the first 450 patients enrolled in ABSORB EXTEND who have completed 12 months follow-up. METHODS AND RESULTS Clinical event data from the first 450 patients enrolled in ABSORB EXTEND have demonstrated low rates of ischaemia-driven MACE (4.2%) and target vessel failure (4.7%) at 12 months. There have been seven cases of device failure in this study: three cases of scaffold dislodgement (0.67%) and four cases of subacute or late scaffold thrombosis (0.89%). All scaffold dislodgements occurred in the left circumflex (LCX), and in two cases dislodgement was observed after reinsertion of the same device. Two cases of subacute scaffold thrombosis and two late scaffold thromboses were observed. Two out of four cases of scaffold thrombosis seemed to be related to either premature discontinuation of dual antiplatelet therapy (DAPT) or resistance to clopidogrel. CONCLUSIONS This is the first report specifically describing the incidence and the potential mechanisms of scaffold dislodgement and scaffold thrombosis as seen in the ABSORB EXTEND trial.

Early (before 6 months), late (6-12 months) and very late (after 12 months) angiographic scaffold restenosis in the ABSORB cohort B trial

AIMS The long-term follow-up of the first-in-man ABSORB Cohort B trial showed that angiographic binary restenosis can occur early, late or very late after implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS). Since the mechanical support of the scaffold decreases during bioresorption, the mechanism of in-segment restenosis (ISR) of the Absorb BVS might be different from that of metallic stents. The objective of the current analysis was to review the multimodality imaging of cases with binary restenosis to elucidate the mechanism of ISR after Absorb BVS implantation. METHODS AND RESULTS The ABSORB Cohort B trial enrolled 101 patients with a maximum of two de novo coronary lesions. At the three-year imaging and clinical follow-up, there were six cases of in-segment binary restenosis: two early ISR (<6 months), one late ISR (6-12 months) and three very late ISR (>12 months). Three of these ISR cases seemed to be induced by anatomical or procedural factors. In the other three cases, intravascular imaging (IVUS/OCT) demonstrated that the main mechanism of restenosis was significant intra-scaffold tissue growth, while the structural circularity and diameter of the scaffold were not affected. CONCLUSIONS Early and late restenosis after implantation of the Absorb bioresorbable scaffold could be related to anatomical or procedural factors. In this small cohort of patients late or very late restenosis seems to be attributed to pure intra-scaffold tissue growth without extrinsic encroachment of the scaffold.

Impact of Contrast-Induced Nephropathy and Cardiovascular Events by Serum Cystatin C in Renal Insufficiency Patients Undergoing Cardiac Catheterization

We assessed the usefulness of serum cystatin C for predicting contrast-induced nephropathy (CIN) in patients (n = 100) undergoing coronary catheterization. After a 12-month follow-up, the incidence of CIN was 8.3% (n = 5) in patients with mild renal insufficiency (estimated glomerular filtration rate [eGFR] 60-89 mL/min per 1.73 m2), 34.4% (n = 10) in those with moderate renal insufficiency (eGFR 30-59 mL/min per 1.73 m2), and 100% (n = 3) in those with severe renal insufficiency (eGFR 15-29 mL/min per 1.73 m2). The sensitivity was 81.8% and specificity was 90.9% at the cutoff level of serum cystatin C >1.18 mg/L. Serum cystatin C levels were significantly (P < .001) higher in the patients with moderate renal insufficiency in the CIN group than those in the non-CIN group. Multivariate logistic regression analysis demonstrated that baseline serum cystatin C independently predicted short-term mortality (odds ratio [OR], 0.311; 95% confidence interval [CI] 0.058-0.538; P = .026). Baseline serum cystatin C significantly predicted the occurrence of CIN in the patients with moderate renal insufficiency.

In vitro validation and comparison of different software packages or algorithms for coronary bifurcation analysis using calibrated phantoms: Implications for clinical practice and research of bifurcation stenting

The accuracy and precision of quantitative coronary angiography (QCA) software dedicated for bifurcation lesions compared with conventional single‐vessel analysis remains unknown. Furthermore, comparison of different bifurcation analysis algorithms has not been performed.

Incidence and Potential Mechanism(s) of Post-Procedural Rise of Cardiac Biomarker in Patients With Coronary Artery Narrowing After Implantation of an Everolimus-Eluting Bioresorbable Vascular Scaffold or Everolimus-Eluting Metallic Stent.

OBJECTIVES This study sought to evaluate the mechanism of post-procedural cardiac biomarker (CB) rise following device implantation. BACKGROUND A fully bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents (EES), might be associated with a higher incidence of periprocedural myocardial injury. METHODS In 501 patients with stable or unstable angina randomized to either Absorb (335 patients) or EES (n = 166) in the ABSORB II trial, 3 types of CB (creatine kinase, creatine kinase-myocardial band, and troponin) were obtained before and after procedure. Per protocol, periprocedural myocardial infarction (PMI) was defined as creatine kinase rise >2× the upper limit of normal with creatine kinase-myocardial band rise. RESULTS Incidence of side branch occlusion and any anatomic complications assessed by angiography was similar between the 2 treatment arms (side branch occlusion: Absorb: 5.3% vs. Xience: 7.6%, p = 0.07; any anatomic complication: Absorb: 16.4% vs. EES: 19.9%, p = 0.39). Fourteen patients who presented with recent myocardial infarction at entry with normalized creatine kinase-myocardial band according to the protocol were excluded for post-CB analysis. The overall compliance for CB was 97.8%. The CB rise subcategorized in 7 different ranges was comparable between the 2 treatment arms. PMI rate was numerically higher in the Absorb arm according to the per-protocol definitions, and treatment with overlapping devices was the only independent determinant of per-protocol PMI (odds ratio: 5.07, 95% confidence interval: 1.78 to 14.41, p = 0.002). CONCLUSIONS There were no differences in the incidence of CB rise and PMI between Absorb and EES. Device overlap might be a precipitating factor of myocardial injury. (ABSORB II Randomized Clinical Trial: A Clinical Evaluation to Compare the Safety, Efficacy, and Performance of Absorb Everolimus Eluting Bioresorbable Vascular Scaffold System Against Xience Everolimus Eluting Coronary Stent System in the Treatment of Subjects With Ischemic Heart Disease Caused by De Novo Native Coronary Artery Lesions [ABSORB II]; NCT01425281).

Inter–Core Lab Variability in Analyzing Quantitative Coronary Angiography for Bifurcation Lesions: A Post-Hoc Analysis of a Randomized Trial

OBJECTIVES This study sought to evaluate inter-core lab variability in quantitative coronary angiography (QCA) analysis of bifurcation lesions. BACKGROUND QCA of bifurcation lesions is challenging. To date there are no data available on the inter-core lab variability of bifurcation QCA analysis. METHODS The randomized Tryton IDE (Tryton Pivotal IDE Coronary Bifurcation Trial) compared the Tryton Side Branch Stent (Tryton Medical, Durham, North Carolina) with balloon angioplasty as side branch treatment. QCA was performed in an angiographic subcohort (n = 326) at 9-month follow-up. Inter-core lab variability of QCA analysis between the Cardiovascular Research Foundation and the Cardialysis core labs was evaluated before and after alignment of the used QCA methodology using angiographic data derived from this angiographic follow-up cohort. RESULTS In the original analysis, before alignment of QCA methodology, the mean difference between the core labs (bias) was large for all QCA parameters with wide 95% limits of agreement (1.96 × SD of the bias), indicating marked variability. The bias of the key angiographic endpoint of the Tryton trial, in-segment percentage diameter stenosis (%DS) of the side branch, was 5.5% (95% limits of agreement: -26.7% to 37.8%). After reanalysis, the bias of the in-segment %DS of the side branch reduced to 1.8% (95% limits of agreement: -16.7% to 20.4%). Importantly, after alignment of the 2 core labs, there was no longer a difference between both treatment groups (%DS of the side branch: treatment group A vs. group B: 34.4 ± 19.4% vs. 32.4 ± 16.1%, p = 0.340). CONCLUSIONS Originally, a marked inter-core lab variability of bifurcation QCA analysis was found. After alignment of methodology, inter-core lab variability decreased considerably and impacted angiographic trial results. This latter finding emphasizes the importance of using the same methodology among different core labs worldwide. (Tryton Pivotal Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

Scaffold and Edge Vascular Response Following Implantation of Everolimus-Eluting Bioresorbable Vascular Scaffold: A 3-Year Serial Optical Coherence Tomography Study

OBJECTIVES This study sought to investigate the in-scaffold vascular response (SVR) and edge vascular response (EVR) after implantation of an everolimus-eluting bioresorbable scaffold (BRS) using serial optical coherence tomography (OCT) imaging. BACKGROUND Although studies using intravascular ultrasound have evaluated the EVR in metal stents and BRSs, there is a lack of OCT-based SVR and EVR assessment after BRS implantation. METHODS In the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study, 23 patients (23 lesions) in Cohort B1 and 17 patients (18 lesions) in Cohort B2 underwent truly serial OCT examinations at 3 different time points (Cohort B1: post-procedure, 6 months, and 2 years; B2: post-procedure, 1 year, and 3 years) after implantation of an 18-mm scaffold. A frame-by-frame OCT analysis was performed at the 5-mm proximal, 5-mm distal edge, and 2-mm in-scaffold margins, whereas the middle 14-mm in-scaffold segment was analyzed at 1-mm intervals. RESULTS The in-scaffold mean luminal area significantly decreased from baseline to 6 months or 1 year (7.22 ± 1.24 mm(2) vs. 6.05 ± 1.38 mm(2) and 7.64 ± 1.19 mm(2) vs. 5.72 ± 0.89 mm(2), respectively; both p < 0.01), but remained unchanged from then onward. In Cohort B1, a significant increase in mean luminal area of the distal edge was observed (5.42 ± 1.81 mm(2) vs. 5.58 ± 1.53 mm(2); p < 0.01), whereas the mean luminal area of the proximal edge remained unchanged at 6 months. In Cohort B2, the mean luminal areas of the proximal and distal edges were significantly smaller than post-procedure measurements at 3 years. The mean luminal area loss at both edges was significantly less than the mean luminal area loss of the in-scaffold segment at both 6-month and 2-year follow-up in Cohort B1 or at 1 year and 3 years in Cohort B2. CONCLUSIONS This OCT-based serial EVR and SVR evaluation of the Absorb Bioresorbable Vascular Scaffold (Abbott Vascular, Santa Clara, California) showed less luminal loss at the edges than luminal loss within the scaffold. The luminal reduction of both edges is not a nosologic entity, but an EVR in continuity with the SVR, extending from the in-scaffold margin to both edges. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Bioresorption and Vessel Wall Integration of a Fully Bioresorbable Polymeric Everolimus-Eluting Scaffold: Optical Coherence Tomography, Intravascular Ultrasound, and Histological Study in a Porcine Model With 4-Year Follow-Up.

OBJECTIVES The aim of the present study was to investigate the relationship between the integration process and luminal enlargement with the support of light intensity (LI) analysis on optical coherence tomography (OCT), echogenicity analysis on intravascular ultrasound, and histology up to 4 years in a porcine model. BACKGROUND In pre-clinical and clinical studies, late luminal enlargement has been demonstrated at long-term follow-up after everolimus-eluting poly-l-lactic acid coronary scaffold implantation. However, the time relationship and the mechanistic association with the integration process are still unclear. METHODS Seventy-three nonatherosclerotic swine that received 112 Absorb scaffolds were evaluated in vivo by OCT, intravascular ultrasound, and post-mortem histomorphometry at 3, 6, 12, 18, 24, 30, 36, 42, and 48 months. RESULTS The normalized LI, which is the signal densitometry on OCT of a polymeric strut core normalized by the vicinal neointima, was able to differentiate the degree of connective tissue infiltration inside the strut cores. Luminal enlargement was a biphasic process at 6 to 18 months and at 30 to 42 months. The latter phase occurred with vessel wall thinning and coincided with the advance integration process demonstrated by the steep change in normalized LI (0.26 [interquartile range (IQR): 0.20 to 0.32] at 30 months versus 0.68 [IQR: 0.58 to 0.83] at 42 months, p < 0.001). CONCLUSIONS In this pre-clinical model, late luminal enlargement relates to strut integration into the arterial wall. Quantitative LI analysis on OCT could be used as a surrogate method for monitoring the integration process of poly-l-lactic acid scaffolds, which could provide insight and understanding on the imaging-related characteristics of the bioresorption process of polylactide scaffolds in human.