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

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).

Amsterdam Investigator-initiateD Absorb strategy all-comers trial (AIDA trial): a clinical evaluation comparing the efficacy and performance of ABSORB everolimus-eluting bioresorbable vascular scaffold strategy vs the XIENCE family (XIENCE PRIME or XIENCE Xpedition) everolimus-eluting coronary stent strategy in the treatment of coronary lesions in consecutive all-comers: rationale and study design.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (AbsorbBVS) is a completely resorbable device engineered to overcome the limitations of permanent metallic stents, providing temporary scaffolding and antiproliferative drug delivery for the treatment of obstructive coronary artery disease. METHODS: The objective of the AIDA trial is to evaluate the efficacy and performance in an contemporary all-comer population of the AbsorbBVS strategy vs the XIENCE family everolimus-eluting metallic coronary stent system in the treatment of coronary lesions. The AIDA trial is a prospective, randomized (1:1), active-control, single-blinded, all-comer, noninferiority trial. A total of 2,690 subjects will be enrolled with broad inclusion and limited exclusion criteria according to the "Instructions for Use" of the AbsorbBVS strategy. The study population includes both simple and complex lesions, in patients with stable and acute coronary syndrome. The follow-up continues for 5years. The primary end point of the trial is target vessel failure, defined as the composite of cardiac death, myocardial infarction, and target vessel revascularization, at 2years. This study is registered on ClinicalTrials.gov with number NCT01858077. CONCLUSION: The AIDA trial will provide the first randomized direct comparison between the everolimus-eluting bioresorbable vascular scaffold and the everolimus-eluting metallic stent in contemporary percutaneous coronary intervention practice.

Applying the National Institute for Clinical Excellence criteria to patients treated with the Genous™ Bio-engineered R stent™: a sub-study of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry.

The National Institute for Clinical Excellence (NICE) guidelines recommend the use of bare-metal stents (BMS) in non-complex lesions with a low risk of restenosis (diameter ≥3 mm and lesion length ≤15 mm) and the use of drug-eluting stents (DES) in more complex lesions with a high risk of restenosis (diameter <3.0 mm or lesion length >15 mm). However, the guidelines were created based on studies evaluating BMS and DES only. We performed an analysis of patients undergoing non-urgent percutaneous coronary intervention with the novel endothelial cell capturing stent (ECS). The ECS is coated with CD34(+) antibodies that attract circulating endothelial progenitor cells to the stent surface, thereby accelerating the endothelialization of the stented area. We analyzed all patients enrolled in the worldwide e-HEALING registry that met the NICE criteria for either low-risk or high-risk lesions and were treated with ≥1 ECS. The main study outcome was target vessel failure (TVF) at 12-month follow-up, defined as the composite of cardiac death or MI and target vessel revascularization (TVR). A total of 4,241 patients were assessed in the current analysis. At 12-month follow-up, TVF occurred in 7.0% of the patients with low-risk lesions and in 8.8% of the patients with high-risk lesions (p = 0.045). When evaluating the diabetic patients versus the non-diabetic patients per risk group, no significant differences were found in TVF, MI or TVR in either risk group. The ECS shows good clinical outcomes in lesions carrying either a high or a low risk of restenosis according to the NICE guidelines with comparable rates of cardiac death, myocardial infarction, and stent thrombosis. The TVF rate with ECS was slightly higher in patients with high-risk lesions, driven by higher clinically driven TLR. The risk of restenosis with ECS in patients carrying high-risk lesions needs to be carefully considered relative to other risks associated with DES. Furthermore, the presence of diabetes mellitus did not influence the incidence of TVF in either risk group.

One-year clinical outcome in an unselected patient population treated with the Genous™ endothelial progenitor cell capturing stent.

OBJECTIVE: We assessed the 1-year clinical outcome in a large cohort of unselected patients treated with an endothelial progenitor cell (EPC) capturing coronary stent. BACKGROUND: The novel EPC capturing stent is coated with CD34+ antibodies that bind circulating EPCs to the stent surface, thereby accelerating endothelialization of the stent struts; it is hypothesized that this may prevent restenosis and stent thrombosis. METHODS: A total of 405 unselected patients were treated percutaneously with the EPC capturing stent. The majority of patients had complex lesions with an estimated high risk of restenosis. RESULTS: The primary endpoint defined as the composite of cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) at 1-year was 13.3%, mainly attributable to TLR which was 10.9%. The occurrence of definite and probable ST was low, 0.5 and 0.7%, respectively. Based on the risk of restenosis, in patients with an estimated high risk of restenosis (n = 249), the composite primary endpoint was 16.1% versus 9.0% in patients with an estimated low risk (n = 155). Moreover, the 1 year clinical outcomes in diabetic patient compared well with the nondiabetic patients. CONCLUSION: In this single-center study, the 1-year clinical follow-up in a "real-world" population treated with the EPC capturing stent showed good results. Currently, large randomized studies are conducted to evaluate the long-term safety and efficacy of this stent.

Neointimal hyperplasia of ultra-thin stents with microcrystalline sirolimus or durable polymer everolimus-eluting stents: 6- and 24-month results of the DESSOLVE III OCT study.

AIMS: The DESSOLVE III OCT substudy aimed to compare serially neointimal hyperplasia volume obstruction (%VO) between the thin-strut MiStent with early polymer elimination and nine-month sustained drug release from microcrystalline sirolimus and the durable polymer-coated everolimus-eluting XIENCE stent at six and 24 months after implantation. METHODS AND RESULTS: The efficacy endpoint was %VO, calculated as abluminal neointimal volume/stent volume. Thirty-six patients (MiStent 16 patients, 16 lesions; XIENCE 20 patients, 22 lesions) underwent serial OCT evaluation at both six and 24 months. At six months, mean abluminal %VO was significantly lower in the MiStent group than in the XIENCE group (14.54±3.70% vs 19.11±6.70%; p=0.011), whereas the difference in %VO between the two groups decreased at 24 months (20.88±5.72% vs 23.50±7.33%; p=0.24). There was no significant difference in percentage malapposed struts and percentage uncovered struts between the two groups at both time points. CONCLUSIONS: In the serial comparative OCT analysis of the MiStent versus the XIENCE, the MiStent showed a more favourable efficacy for preventing neointimal formation with comparable strut tissue coverage, as compared with the XIENCE at six months, but this difference in %VO decreased at 24 months so that the difference in neointima at 24 months was no longer significant.

Clinical outcomes of bioabsorbable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: two-year follow-up of the DESSOLVE III trial.

AIMS: The aim of this study was to assess whether the nine months of cytostatic inhibition by crystalline sirolimus has a beneficial effect in the two-year follow-up in an all-comer population undergoing percutaneous coronary intervention. METHODS AND RESULTS: The DESSOLVE III study (n=1,398) is a prospective, all-comer, multicentre, randomised controlled study (NCT02385279) allocating 703 patients to receive the MiStent drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall, and 695 patients to receive the XIENCE durable polymer everolimus-eluting stent. At two years, the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction [TV-MI], and clinically indicated target lesion revascularisation [TLR]) occurred in 8.7% and 8.6% (p=0.958) of patients, and the patient-oriented composite endpoint (all deaths, all MI, and all revascularisations) was observed in 18.5% and 19.6% (p=0.598) of patients in the MiStent and XIENCE arms, respectively. The frequency of TV-MI and clinically indicated TLR was also comparable for both stent types. The rate of definite/probable stent thrombosis was not different in the two arms (0.9% vs 1.3%, p=0.435). CONCLUSIONS: In an all-comer population, at two-year follow-up, the use of the MiStent sirolimus-eluting bioabsorbable polymer-coated stent was at least as safe and efficacious as the XIENCE durable polymer stent. The MiStent's potential long-term clinical benefit will be further elucidated after five years of follow-up.

1-Year Clinical Outcomes of All Comers Treated With 2 Bioresorbable Polymer-Coated Sirolimus-Eluting Stents: Propensity Score-Matched Comparison of the COMBO and Ultrathin-Strut Orsiro Stents.

OBJECTIVES: The aim of this study was to determine 1-year safety and efficacy after treatment with the COMBO and Orsiro stents. BACKGROUND: The COMBO stainless-steel stent has an anti-CD34+ antibody coating to capture endothelial progenitor cells, thereby promoting faster endothelialization. The Orsiro is an ultrathin-strut cobalt-chromium stent, covered by an extremely thin layer of amorphous silicon carbide to minimize ion leakage. Both devices elute sirolimus from biodegradable polymers. METHODS: For this analysis we included European patients from the COMBO collaboration, a patient-level pooling of 2 prospective all-comers registries of COMBO stent implantation (n = 2,775), and all patients randomized to the Orsiro stent (n = 1,169) from the Dutch BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) randomized trial. The main outcome of interest was 1-year target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization evaluated using propensity score-matched analysis. RESULTS: At baseline, COMBO patients were older and had more insulin-treated diabetes, renal insufficiency, and other comorbidities. However, Orsiro patients included more current smokers and more acute coronary syndrome presentations. Orsiro patients also received longer stents and had more complex target lesions. After propensity score-matched analysis (n = 862/arm), 1-year target lesion failure occurred in 4.1% of COMBO-treated and 2.7% of Orsiro-treated patients (hazard ratio: 1.55; 95% confidence interval: 0.92 to 2.62; p = 0.10). Definite stent thrombosis occurred in 0.5% of COMBO-treated and 0.5% of Orsiro-treated patients (p = 0.99). CONCLUSIONS: A propensity score-matched comparison of all comers treated with the COMBO or Orsiro stent showed no statistically significant differences. Stent thrombosis risk was low and similar between the stents. (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population [BIO-RESORT], NCT01674803; MASCOT-Post Marketing Registry [MASCOT], NCT02183454; Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE Reg], NCT01874002).

Final 3-Year Outcomes of MiStent Biodegradable Polymer Crystalline Sirolimus-Eluting Stent Versus Xience Permanent Polymer Everolimus-Eluting Stent: Insights From the DESSOLVE III All-Comers Randomized Trial.

BACKGROUND: Numerous randomized clinical trials have demonstrated the superiority of thin-strut biodegradable polymer second-generation drug-eluting stent to the first-generation drug-eluting stent and the noninferiority to the thin-strut second-generation permanent polymer drug-eluting stent. Data on long-term clinical outcomes with a novel ultrathin drug-eluting stent, to date, are limited. METHODS: The DESSOLVE III trial (Multicenter Randomized Study of the MiStent Sirolimus Eluting Absorbable Polymer Stent System for Revascularization of Coronary Arteries; n=1398) is a prospective, multicenter, single-blinded, all-comers, randomized controlled trial (NCT02385279), allocating in a 1:1 ratio to either ultrathin-strut biodegradable polymer MiStent sirolimus-eluting stent or to thin-strut permanent polymer Xience everolimus-eluting stent. The primary end point was device-oriented composite end point, defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. The secondary end point was patient-oriented composite end point, defined as the composite of all-cause mortality, any myocardial infarction, or any revascularization. RESULTS: At 3 years, follow-up data were available in 1381 patients (98.8%). The primary end point of device-oriented composite end point occurred in 10.5% for MiStent sirolimus-eluting stent and in 11.5% for Xience everolimus-eluting stent (P=0.55). Rates of cardiac death (3.9% versus 3.8%; P=0.88), target vessel myocardial infarction (3.2% versus 2.5%; P=0.43), and clinically indicated target lesion revascularization (5.2% versus 6.5%; P=0.30) did not differ significantly between the 2 devices. The rate of definite or probable stent thrombosis was infrequent and similar between the 2 arms (1.2% versus 1.5%; P=0.64). The 90-day landmark analysis showed no significant difference in device-oriented composite end point between the 2 groups after polymer degradation of MiStent. The risk of patient-oriented composite end point was comparable between the 2 groups (22.7% versus 22.9%; P=0.34). CONCLUSIONS: In the DESSOLVE III trial, early safety and efficacy with MiStent sirolimus-eluting bioabsorbable polymer-coated stent are confirmed at a longer term follow-up when compared with Xience everolimus-eluting permanent polymer-coated stent in a large all-comers population. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385279.

Comparison of One-Year Outcomes in Patients >75 Versus ≤75 Years With Coronary Artery Disease Treated With COMBO Stents (From The MASCOT Registry).

Older patients who undergo coronary interventions are at greater risk of ischemic events and less likely to tolerate prolonged dual antiplatelet therapy (DAPT) due to bleeding risk. The COMBO biodegradable polymer sirolimus-eluting stent promotes rapid endothelialization through endothelial progenitor cell capture technology which may be advantageous in elderly patients. We compared 1-year clinical outcomes and DAPT cessation events in patients >75 versus ≤75 years from the MASCOT registry. MASCOT was a prospective, multicenter cohort study of all-comers undergoing attempted COMBO stenting. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a nontarget vessel or clinically driven target lesion revascularization. Bleeding was adjudicated using the Bleeding Academic Research Consortium criteria. Adjusted outcomes were analyzed using Cox regression methods. The study included 18% (n = 479) patients >75 years and 72% (n = 2,135) patients ≤75 years. One-year TLF occurred in 4.6% patients >75 years versus 3.1% patients ≤75years of age, p = 0.10; adj hazard ratio 1.36, 95% confidence intervals 0.77 to 2.38, p = 0.29. There were no significant differences in cardiac death (1.7% vs 1.3%, p = 0.55), MI (2.1% vs 1.2%, p = 0.14), target lesion revascularization (1.7% vs 1.4%, p = 0.60) and definite stent thrombosis (0.8% vs 0.4%, p = 0.19). Major Bleeding Academic Research Consortium 3,5 bleeding (3.1% vs 1.5%, p = 0.01) and DAPT cessation rates (32.4% vs 23.0%, p <0.001) were significantly higher in elderly patients. In conclusion, elderly patients >75 years treated with COMBO stents had similar TLF but significantly greater incidence of bleeding than younger patients and DAPT cessation in one-third of patients over 1 year.

A Randomized Comparison of Paclitaxel-Eluting Balloon Versus Everolimus-Eluting Stent for the Treatment of Any In-Stent Restenosis: The DARE Trial.

OBJECTIVES: The authors sought to evaluate the relative performance of a drug-eluting balloon (DEB) and a drug-eluting stent (DES) in patients with any (bare-metal or drug-eluting stent) in-stent restenosis (ISR). BACKGROUND: The treatment of ISR remains challenging in contemporary clinical practice. METHODS: In a multicenter randomized noninferiority trial, patients with any ISR were randomly allocated in a 1:1 fashion to treatment with a DEB (SeQuent Please paclitaxel-eluting balloon, B. Braun Melsungen, Melsungen, Germany), or a DES (XIENCE everolimus-eluting stent, Abbott Vascular, Santa Clara, California). The primary endpoint was noninferiority in terms of in-segment minimal lumen diameter (MLD) at 6-month angiographic follow-up. Secondary endpoints included angiographic parameters at 6 months and clinical follow-up up to 12 months. RESULTS: A total of 278 patients, of whom 56% had DES-ISR, were randomized at 8 sites to treatment with DEB (n = 141) or DES (n = 137). As compared with DEB, DES was associated with larger MLD and lower % stenosis immediately post-procedure (1.84 ± 0.46 vs. 1.72 ± 0.35; p = 0.018; and 26 ± 10% vs. 30 ± 10%; p = 0.03). Angiographic follow up was completed at 196 ± 53 days in 79% of patients. With respect to the primary endpoint of in-segment MLD at 6 months, DEB was noninferior to DES (DEB 1.71 ± 0.51 mm vs. DES 1.74 ± 0.61 mm; p for noninferiority <0.0001). Target vessel revascularization at 12-month follow-up was similar in both groups (DES 7.1% vs. DEB 8.8%; p = 0.65). CONCLUSIONS: In patients with ISR, treatment with DEB was noninferior compared with DES in terms of 6-month MLD. There were no differences in clinical endpoints, including target vessel revascularization up to 12 months. Therefore, use of a DEB is an attractive treatment option for in-stent restenosis, withholding the need for additional stent implantation.

Evaluation of the MiStent sustained sirolimus eluting biodegradable polymer coated stent for the treatment of coronary artery disease: does uniform sustained abluminal drug release result in earlier strut coverage and better safety profile?

INTRODUCTION: Treatment of coronary artery disease has made strides over the last decades. Development of drug eluting stents (DES), coated with a polymer layer and an anti-proliferative drug to reduce neointimal hyperplasia, has reduced the incidence of in-stent-restenosis relative to treatment with bare metal stents. Patients treated with first generation DES more likely suffer from (very) late events which can be cause by the permanent presence of a polymer. Therefore second generation DES with more biocompatible coatings, and third generation DES, with very thin struts coated with biodegradable polymers, were developed. Areas covered: The MiStent SES is one of these third generation DES and is designed to limit the duration of polymer exposure, optimize coronary vessel healing and more precisely and consistently control drug elution to improve safety and clinical outcomes. This review provides a detailed description of the technique behind the MiStent SES, and describes the pre-clinical and clinical trials conducted with this device to date. Expert commentary: Recent clinical trials have shown non-inferiority of very thin strut biodegradable polymer coated DES compared to durable polymer coated DES, whilst maintaining an excellent safety profile. Longer follow-up, to see the real potential benefits of these devices, is mandatory however.

The REMEDEE-OCT Study: An Evaluation of the Bioengineered COMBO Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent Compared With a Cobalt-Chromium Everolimus-Eluting Stent in Patients With Acute Coronary Syndromes: Insights From Optical Coherence Tomography Imaging Analysis.

OBJECTIVES: The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes. BACKGROUND: CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell-capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed. METHODS: In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis. RESULTS: The percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level-based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models-adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 µm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days. CONCLUSIONS: The present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.

One-Year Clinical Outcomes of Patients Presenting With ST-Segment Elevation Myocardial Infarction Caused by Bifurcation Culprit Lesions Treated With the Stentys Self-Apposing Coronary Stent: Results From the APPOSITION III Study.

OBJECTIVE: To investigate outcomes in patients with ST-segment elevation myocardial infarction (STEMI) after treatment with the Stentys self-apposing stent (Stentys SAS; Stentys S.A.) for bifurcation culprit lesions. BACKGROUND: The nitinol, self-expanding Stentys was initially developed as a dedicated bifurcation stent. The stent facilitates a provisional strategy by accommodating its diameter to both the proximal and distal reference diameters and offering an opportunity to "disconnect" the interconnectors, opening the stent toward the side branch. METHODS: The APPOSITION (a post-market registry to assess the Stentys self-expanding coronary stent in acute myocardial infarction) III study was a prospective, multicenter, international, observational study including STEMI patients undergoing primary percutaneous coronary intervention (PCI) with the Stentys SAS. Clinical endpoints were evaluated and stratified by bifurcation vs non-bifurcation culprit lesions. RESULTS: From 965 patients included, a total of 123 (13%) were documented as having a bifurcation lesion. Target-vessel revascularization (TVR) rates were higher in the bifurcation subgroup (16.4% vs 10.0%; P=.04). Although not statistically significant, other endpoints were numerically higher in the bifurcation subgroup: major adverse cardiac events (MACE; 12.7% vs 8.8%), myocardial infarction (MI; 3.4% vs 1.8%), and definite/probable stent thrombosis (ST; 5.8% vs 3.1%). However, when postdilation was performed, clinical endpoints were similar between bifurcation and non-bifurcation lesions: MACE (8.7% vs 8.4%), MI (1.2% vs 0.7%), and definite/probable ST (3.7% vs 2.4%). CONCLUSIONS: The use of the Stentys SAS was safe and feasible for the treatment of bifurcation lesions in the setting of primary PCI for STEMI treatment with acceptable 1-year cardiovascular event rates, which improved when postdilation was performed.

Evaluation of vascular healing of polymer-free sirolimus-eluting stents in native coronary artery stenosis: a serial follow-up at three and six months with optical coherence tomography imaging.

AIMS: Our aim was to assess vascular response after polymer-free sirolimus-eluting stent (SES) implantation by using an optical coherence tomography (OCT)-derived vascular healing score (HS), quantifying the deficiency of healing. METHODS AND RESULTS: In a prospective, multicentre, single-arm, open-label study, OCT examinations were performed at three months in 45 patients (47 lesions). Per protocol, 24 lesions which had not reached adequate vascular healing according to study criteria were scheduled for OCT examination at six months. The HS was calculated at two time points. Serial OCT imaging demonstrated that the proportion of covered stent struts increased from a median of 87.1% at three months to 98.6% at six months (p<0.001). The neointimal thickness increased from a median of 82.8 µm to 112.2 µm (p<0.001), whereas the median percentages of malapposed struts were 0.2% and 0.0% at the two respective time points. Neointimal volume obstruction increased from 6.3% to 12.8%, and the HS decreased from a median of 28.1 at three months to 2.4 at six months. CONCLUSIONS: In patients who had inadequate vascular healing three months after polymer-free SES implantation, serial OCT showed almost complete vascular healing at six months.

Is quantitative coronary angiography reliable in assessing the lumen gain after treatment with the everolimus-eluting bioresorbable polylactide scaffold?

AIMS: The current study aimed to assess the difference in lumen dimension measurements between optical coherence tomography (OCT) and quantitative coronary angiography (QCA) in the polymeric bioresorbable scaffold and metallic stent. METHODS AND RESULTS: In the randomised ABSORB Japan trial, 87 lesions in the Absorb arm and 44 lesions in the XIENCE arm were analysed. Post-procedural OCT-QCA lumen dimensions were assessed in matched proximal/distal non-stented/non-scaffolded reference (n=199), scaffolded (n=145) and stented (n=75) cross-sections at the two device edges using the Bland-Altman method. In the non-stented/non-scaffolded reference segments, QCA systematically underestimated lumen diameter (LD) compared with OCT (accuracy, -0.26 mm; precision, 0.47 mm; 95% limits of agreement as a mean bias±1.96 standard deviation, -1.18-0.66 mm). When compared to OCT, QCA of the Absorb led to a more severe underestimation of the LD (-0.30 mm; 0.39 mm; -1.06-0.46 mm) than with the XIENCE (-0.14 mm; 0.31 mm; -0.75-0.46 mm). QCA underestimated LD by 9.1%, 4.9%, and 9.8% in the reference, stented, and scaffolded segments, respectively. The protrusion distance of struts was larger in the Absorb arm than in the XIENCE arm (135±27 µm vs. 18±26 µm, p<0.001), and may have contributed to the observed differences. CONCLUSIONS: In-device QCA measurement was differently affected by the presence of a metallic or polymeric scaffold, a fact that had a significant impact on the QCA assessment of acute gain and post-procedural minimum LD.

Coronary Artery Vessel Healing Pattern, Short and Long Term, After Implantation of the Everolimus-Eluting Bioresorbable Vascular Scaffold.

BACKGROUND: Although the Absorb bioresorbable vascular scaffold is increasingly used in daily clinical practice for the treatment of coronary artery disease, the exact vascular healing pattern and the resorption process in humans is unknown because histological data are derived only from animal studies. METHODS AND RESULTS: We have obtained 4 autopsies (5 scaffolds) since August 2013. Duration of bioresorbable vascular scaffold implantation ranged from 3 to 501 days. All autopsies and histological assessments were performed by dedicated cardiovascular pathologists. At 1 week after bioresorbable vascular scaffold implantation, struts were covered with a fine layer of fibrin and platelets. At 113 days, the scaffold struts were fully covered with smooth muscle cells. Hyaline eosinophilic and proteoglycan material infiltrating the scaffold struts was observed at 501 days after implantation. At all time points, we observed the presence of multinuclear foreign body giant cells adjacent to the scaffold struts. CONCLUSIONS: Resorption and healing processes after bioresorbable vascular scaffold implantation in human patients mirror those observed in porcine models. The presence of multinucleated foreign body giant cells at both short- and long-term follow-up needs further investigation and may be related to a low-grade absorptive inflammatory response to the polymer.

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits.

BACKGROUND: The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface. METHODS: Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 µg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions. RESULTS: Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation. CONCLUSION: We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.

Distal embolization of hydrophilic-coating material from coronary guidewires after percutaneous coronary interventions.

BACKGROUND: Coronary guidewires are indispensable during percutaneous coronary interventions. Nowadays, most guidewires have hydrophilic coatings to improve their trackability, allowing easy lesion passage and facilitating balloon and stent positioning. Recent reports, however, have raised concerns about detachment and subsequent embolization of these hydrophilic coatings. METHODS AND RESULTS: We have retrospectively reviewed the histological samples of the myocardium, obtained during autopsies in the period 2009 to 2013, from all patients who had a history of percutaneous coronary interventions (n=40). Foreign material was observed in the distal myocardium in 4 patients (10%). Furthermore, we have reviewed 205 thrombus specimens which were obtained during thrombus aspiration in the setting of primary percutaneous coronary interventions in the period 2005 to 2009. In 45% of the cases, foreign material was observed within the thrombus. Finally, we have examined the histopathologic appearance of hydrophilic-guidewire coating material ex vivo by embedding the coating in placenta specimen and cut and stain it in exactly the same manner as the myocardium and thrombus specimen. The histopathologic appearance of the hydrophilic coating ex vivo was identical to the foreign material found in vivo. CONCLUSIONS: Distal embolization of hydrophilic-coating material was observed in 10% of the patients who had a history of percutaneous coronary interventions. Hydrophilic-coating material was found in 45% of coronary thrombus specimen obtained during thrombus aspiration. These findings suggest that detachment and distal embolization of hydrophilic-coating material from coronary guidewires occur more often than the sparse literature on this topic suggests.

Clinical results after coronary stenting with the Genous™ Bio-engineered R stent™: 12-month outcomes of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry.

AIMS: e-HEALING is a worldwide, internet-based registry designed to capture post marketing clinical data on the use of the Genous™ EPC capturing R stent™. Rapid restoration of a healthy endothelial layer after stent placement by capturing circulating endothelial progenitor cells may reduce both stent thrombosis (ST) and in-stent-restenosis. METHODS AND RESULTS: We planned a 5,000 patient registry with ≥1 lesion suitable for stenting. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction (MI) and target vessel revascularisation. Secondary outcomes were the composite of cardiac death, MI or target lesion revascularisation (TLR), and individual outcomes including ST. A total of 4,939 patients received ≥1 Genous stent between 2005 and 2007. Baseline characteristics showed a median age of 63 years, 79% males, 25% diabetics, and 37% with prior MI. A total of 49% of lesions treated were ACC/AHA type B2 or C; 1.1 stents per lesion were used. At 12 months, TVF occurred in 8.4% and the composite of cardiac death, MI or TLR in 7.9%. Twelve-month TLR and ST were 5.7% and 1.1%, respectively. CONCLUSIONS: Coronary stenting with the Genous results in good clinical outcomes, and low incidences of repeat revascularisation and ST.