Late Lumen Loss Research Articles

Modelling, Fabrication by Photo-Chemical Etching and in Vivo Study of Magnesium AZ31 Stents

Magnesium metal (Mg) is a promising material for stent applications due to its biocompatibility and ability to be resorbed by the body. Manufacturing of stents by laser cutting has become an industry standard. However, this expensive approach has challenges. Our alternative approach uses photo-chemical etching to transfer a pattern of the stent onto a Mg sheet. Such a stent has been characterized in vitro and the results are published elsewhere by our group. In this study, we present three stages of creating and validating a stent prototype, which includes design and simulation using finite element analysis, followed by fabrication based on AZ31 alloy and, finally, in vivo testing in peripheral arteries of domestic pigs. Six stents were implanted in two domestic farm pigs weighing 25-28 kg and were allowed to survive for 28 days, with an interim follow-up on day 14. The left and right superficial femoral, the left iliac, and the right renal artery were selected for this study. The diameters of the stented segments were evaluated at the time of implantation, on day 14 and then, finally, on day 28, by quantitative vessel analysis (QVA) using fluoroscopic imaging. Post-implantation angiograms showed good acute gain within the stented segments for all the implanted devices. However, a reduction in lumenal diameter was observed at both the 14th and 28th-day time points. Mean stent stenosis and late lumen loss was recorded as 37 % ± 11 and 1.2 ± 0.55 mm, respectively. Optical Coherence Tomography (OCT) confirmed that although there was a decrease in mean lumenal diameter at 28 days compared to post-implantation, an increase in this diameter was recorded between the interim (14th-day) and terminal (28th-day) time points. OCT imaging displayed some malposition, breaks, stacking, and protrusion into the lumen at the proximal, distal, and mid-sections of the stented arteries. The stents degraded with time, but simultaneously became embedded in the intima. After 28 days, the animals were euthanized, and explanted vessels were fixed for micro-CT imaging and histology studies. Micro-CT imaging revealed stent morphological and volumetric changes due to the in-body degradation. An in vivo corrosion rate of 0.75 mm/year was obtained by the CT evaluation. The histology suggested no-life threatening effects, although moderate injury, inflammation, and endothelialization scores were observed. Additionally, the fibrin score was very low with a high neointimal maturity score at proximal, mid, and distal parts of the vessel with direct contact to the stent. No other stent-related sequelae were reported, including mural thrombus, fibrin deposition in the tunica media (middle layer of the blood vessel) or on the adventitia (outer most layer of the blood vessel), necrosis, nor other potentially adverse findings. The extracted remains of the stents were found to be covered with Mg corrosion by-products typical of the physiological environment.

Sitagliptin attenuates the progression of coronary atherosclerosis in patients with coronary disease and type 2 diabetes

Background and aimsType 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for ASCVD, the aim of this study was to investigate the effects of a dipeptidyl peptidase-4 inhibitor, sitagliptin, on prevention of progression of coronary atherosclerosis assessed by three-dimensional quantitative coronary angiography (3D-QCA) in T2DM patients with coronary artery disease (CAD). MethodsThis was a prospective, randomized, double-center, open-label, blinded end point, controlled 18-month study in patients with CAD and T2DM. A total of 149 patients, who had at least 1 atherosclerotic plaque with 20%–80% luminal narrowing in a coronary artery, and had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention, were randomized to sitagliptin group (n = 74) or control group (n = 75). Atherosclerosis progression was measured by repeat 3D-QCA examination in 88 patients at study completion. The primary outcome was changes in percent atheroma volume (PAV) from baseline to study completion measured by 3D-QCA. Secondary outcomes included change in 3D-QCA-derived total atheroma volume (TAV) and late lumen loss (LLL). ResultsThe primary outcome of PAV increased of 1.69% (95%CL, −0.8%–4.2%) with sitagliptin and 5.12% (95%CL, 3.49%–6.74%) with the conventional treatment (p = 0.023). The secondary outcome of change in TAV in patients treated with sitagliptin increased of 6.45 mm3 (95%CL,-2.46 to 6.36 mm3) and 9.45 mm3 (95%CL,-4.52 to 10.14 mm3) with conventional treatment (p = 0.023), however, no significant difference between groups was observed (p = 0.175). Patients treated with sitagliptin had similar LLL as compared with conventional antidiabetics (−0.06, 95%CL, −0.22 to 0.03 vs. −0.08, −0.23 to −0.03 mm, p = 0.689). ConclusionsIn patients with type 2 diabetes and coronary artery disease, treatment with sitagliptin resulted in a significantly lower rate of progression of coronary atherosclerosis compared with conventional treatment.

Drug-coated Balloon Angioplasty of Femoropopliteal Lesions Maintained Superior Efficacy over Conventional Balloon: 2-year Results of the Randomized EffPac Trial

Background Paclitaxel drug-coated balloon (DCB) catheter angioplasty is the preferred treatment for revascularization of femoropopliteal lesions in peripheral artery disease, but mortality is a safety concern. Purpose To assess 2-year efficacy and safety of DCB angioplasty compared with conventional balloon angioplasty (also known as plain old balloon angioplasty or POBA). Materials and Methods This prospective, multicenter, randomized controlled trial enrolled consecutive participants with symptomatic superficial femoral and/or popliteal artery disease at 11 German centers between September 2015 and December 2016. Participants underwent DCB angioplasty or conventional balloon angioplasty. Primary outcome of 6-month late lumen loss showed superiority of DCB angioplasty over conventional balloon angioplasty. Evaluation at 2 years included secondary outcomes of primary patency and target lesion revascularization (TLR) estimated with Kaplan-Meier analysis, clinical and hemodynamic improvement, quality of life, target limb amputation, and all-cause mortality. Results A total of 171 participants (mean age, 69 years ± 8; 111 men) were evaluated. At 2 years, primary patency was achieved in 90.2% (95% confidence interval [CI]: 80.4%, 95.2%) of DCB angioplasty and 62.7% (95% CI: 50.0%, 73.0%) of conventional balloon angioplasty participants (P < .001). Freedom from TLR occurred in 97.2% (95% CI: 89.1%, 99.3%) of DCB angioplasty and 78% (95% CI: 66.5%, 86.0%) of conventional balloon angioplasty participants (P = .001). The groups did not differ in sustained improvement from baseline to 2 years in Rutherford-Becker category (row mean scores difference, 1.7; P = .19) and showed no difference in mean improvement in the Walking Impairment Questionnaire score (-0.8%; 95% CI: -11.8%, 10.2%; P = .88), EuroQol Group's five-dimension index of quality of life (-0.06; 95% CI: -0.17, 0.03; P = .20), or ankle-brachial index (0.03; 95% CI: -0.08, 0.14; P = .57). No major amputation was necessary. One DCB angioplasty and two conventional balloon angioplasty participants died (risk ratio, 0.48; 95% CI: 0.04, 5.10). Conclusion At 2 years after paclitaxel drug-coated balloon (DCB) angioplasty, primary patency and freedom from target lesion revascularization remained superior compared with conventional balloon angioplasty. DCB angioplasty resulted in sustained clinical and hemodynamic improvement with no increased risk of mortality. © RSNA, 2020 Online supplemental material in available for this article.

Paclitaxel-Coated Balloon vs Uncoated Balloon Angioplasty for Treatment of In-Stent Restenosis in the Superficial Femoral and Popliteal Arteries: The COPA CABANA Trial

Purpose: To investigate the efficacy and sustainability of drug-coated balloon (DCB) treatment of femoropopliteal in-stent restenosis (ISR). Materials and Methods: An investigator-initiated, prospective, multicenter, 1:1 randomized study enrolled 88 patients for treatment of ISR with DCB (n=47; mean age 68.3±9.6 years; 26 men) or uncoated balloon (n=41; mean age 67.6±10.2 years; 26 men) angioplasty (ClinicalTrials.gov identifier NCT01594684). Additionally, the protocol provided for an observational arm composed of patients from either randomized arm who experienced recurrent ISR ≥30 days after the index treatment. Redo treatment consisted of 2 DCBs sequentially inflated at the same location (double dose therapy). The majority of patients (66, 78%) had Rutherford category 3 ischemia. The mean lesion length was 140 mm; a third (27, 31%) were total occlusions. The primary endpoint was angiographic late lumen loss (LLL) at 6 months evaluated by an independent core laboratory. Results: Twenty-two patients (7 DCB +15 uncoated) were treated for recurrence with fully overlapping double DCB angioplasty. Six-month LLL was lower after DCB (0.34±1.12 mm) treatment than after angioplasty with an uncoated balloon (1.58±1.10 mm, p<0.001). At the 12-month follow-up, target lesion revascularization (TLR) was performed in 18 (49%) of 37 patients in the uncoated group, 6 (14%) of 43 patients in the single-dose DCB group (p=0.001), and no patients from the recurrent ISR group. At ~2 years after treatment, a remarkable number (14/27, 52%) of TLRs were recorded in the single-dose DCB group. Conclusion: Treatment with DCBs resulted in significantly less 6-month LLL and fewer TLRs up to 24 months than treatment with uncoated balloons. The double dose for treating recurrent ISR did not cause recognizable adverse events or require TLR up to 24 months.

Inferior Vena Cava Reconstruction in Symptomatic Patients Using Palmaz Stents: A Retrospective Single-Center Experience

The use of stents for treating central venous occlusion is well described. Limited evidence exists related to Palmaz balloon-expandable stent use in inferior vena cava (IVC) reconstruction. We analyzed patency and complication rates after IVC reconstruction using Palmaz stents. From 2002 to 2019, 37 patients (mean age: 51year) underwent IVC reconstruction with 68 Palmaz stents. Indications were symptomatic chronic venous obstruction in the infrarenal (n=25) and intrahepatic (n=12) IVC. Demographic, operative, and imaging data were evaluated. Clinical data, abdominal CT, and/or duplex ultrasound were used to determine patency at follow-up. Restoration of caval patency was achieved in all patients, with complications in 2/37 (5.4%) patients (thrombus formation within the stent; stent embolization eight days after placement). Follow-up data were available for 27 patients. Primary patency was maintained through last follow-up in 19/27 (70%) patients (mean: 1.1year), with successful stent redilation performed in 6 patients. Mean duration of primary-assisted patency (n=5) was 1.2year. Late lumen loss was (n=13) was 40% during a mean time to follow-up of 2.0years. Primary patency in patients with occlusion secondary to malignancy was 109day (range: 1 day-1.0year), whereas primary patency in patients with occlusion from other etiologies was 1.1year (range: 2day-5.9year). The Kaplan-Meier analysis demonstrated primary and primary-assisted patency of 66% and 84%, respectively, at 24 and 48 months. Palmaz balloon-expandable stents for IVC reconstruction is feasible and effective for symptomatic IVC occlusion. Risk of stent migration was low.

Bioresorbable scaffold implantation in STEMI patients: 5\xa0years imaging subanalysis of PRAGUE-19 study

BackgroundBioresorbable scaffold (BRS) Absorb™ clinical use has been stopped due to higher rate of device thrombosis. Scaffold struts persist longer than 2 years in the vessel wall. Second generation devices are being developed. This study evaluates long-term invasive imaging in STEMI patients.MethodsPRAGUE-19 study is an academic study enrolling consecutive STEMI patients with intention to implant Absorb™ BRS. A total of 83 STEMI patients between December 2012 and March 2014 fulfilled entry criteria. Coronary angiography and optical coherence tomography at 5 year follow-up was performed in 25 patients.ResultsPrimary combined clinical endpoint (death, myocardial infarction or target vessel revascularization) occurred in 12.6% during the five-year follow-up with overall mortality 6.3%. Definite scaffold thrombosis occurred in 2 patients in the early phase after BRS implantation. Quantitative coronary angiography after 5 years demonstrated low late lumen loss of 0.11 ± 0.35 mm with binary restenosis rate of 0%. Optical coherence tomography demonstrated complete resorption of scaffold struts and mean lumen diameter of 3.25 ± 0.30 and 3.22 ± 0.49 (P = 0.73) at baseline and after 5 years, respectively. Three patients developed small coronary artery aneurysm in the treated segment.ConclusionInvasive imaging results 5 years after BRS implantation in STEMI showed complete resorption of scaffold struts and stable lumen vessel diameter.Trial registration ISRCTN43696201 (retrospectivelly registred, June 7th, 2019). https://www.isrctn.com/ISRCTN43696201.

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes.

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).

Efficacy and Safety of a Newly Developed Self-Expanding Open-Cell Type Nitinol Stent for Peripheral Arteries: A Preclinical Study in Minipigs

목적얇고 새로운 구조로 개발된 말초동맥용 자가팽창성 개방형 니티놀 스텐트의 유효성 및 안전성을 기존에 사용하는 스텐트와 비교 평가하였다.대상과 방법미니피그 14마리를 대상으로 실험군과 대조군 스텐트를 무작위배정 후 각 개체의 장골동맥에 대칭적으로 삽입하여 1개월(n = 5) 및 6개월(n = 9) 추적관찰하였다. 혈관조영술로 혈관 직경, 후기 내강 손실 및 협착 정도를 평가하고 조직계측학적으로 내탄력층 면적, 내강 면적, 신생 내막 면적 및 협착 정도를 분석하였다. 추적기간 중 모든 실험 개체에 대하여 매일 임상적 평가 및 식이 정도를 추적관찰하였다.결과모든 개체는 추적관찰 기간 중 생존하였으며 중대한 유해 반응을 보이지 않았다. 혈관조영술상 6개월 추적관찰군에서 실험군의 내강 직경이 유의하게 컸으며(p = 0.014), 후기 내강 손실이 적었고(p = 0.019), 협착 정도가 낮았다(p = 0.014). 조직학적으로 1개월 추적관찰군에서 실험군이 신생 내막 면적 및 면적 협착이 유의하게 낮았다(각, p = 0.008, p = 0.016). 6개월 추적관찰군에서는 실험군이 대조군에 비하여 내강 면적이 유의하게 넓었으며(p = 0.040), 내탄력층 면적, 신생 내막 면적 및 면적 협착이 통계적으로 유의하게 낮았다(각, p = 0.004, p = 0.008, p = 0.014).결론새로 개발된 말초혈관용 자가팽창성 개방형 니티놀 스텐트는 기존에 사용하는 스텐트와 비교하여 안전하며 신생 내막 증식의 정도가 적었다.

Over-expansion of second-generation drug-eluting stents, risk of restenosis, and relation to major adverse cardiac events.

The relationship between stent expansion conditions and clinical outcomes is not completely understood. This prospective cohort study included patients who were successfully implanted with second-generation drug-eluting stent in 2012 and received follow-up angiography in 9-12 months. Stent over-expansion was defined as ≥ 1.05 of the stented segment over the reference artery diameter. Imaging parameters were measured, and the follow-up period was 7 years. A total of 123 patients with 161 lesions were enrolled, and 75 (46.58%) stents were found to be over-expanded. The baseline clinical and procedural data were comparable. Stent over-expansion showed a markedly increased diameter stenosis percentage (DSP) at 1-year follow-up (24.12 ± 21.10% vs. 14.65 ± 16.75%, P = 0.002) and high late lumen loss (LLL) in-segment (0.54 ± 0.62 mm vs. 0.31 ± 0.55 mm, P = 0.014). Furthermore, 63 patients with ≥ 1 over-expanded stented lesions were classified into the over-expansion group. Cumulative major cardiac adverse event (MACE) was higher in the over-expansion group than the norm-expansion group (17.5% vs. 8.3%, P = 0.133). Target lesion revascularization/target vessel revascularization increased during the 7-year follow-up period in the over-expansion group compared with the norm-expansion group (11.1% vs. 3.3%, P = 0.098). The Kaplan-Meier cumulative MACE-free survival showed a better tendency for statistical differences in the norm-expansion group than in the over-expansion group (log-rank test; P = 0.083). Conclusion: Stent over-expansion is associated with a significant increase in LLL and DSP at 1-year angiographic follow-up and with the increasing trend of cumulative MACE during 7-year clinical follow-up period compared with stent norm-expansion. Stent over-expansion needs to be avoided.

Clinical outcomes of SeQuent Please paclitaxel-coated balloons for de novo small coronary artery lesion in a Japanese multicenter post-approval registry.

Drug-coated balloon (DCB) angioplasty has emerged as an effective management strategy worldwide. In June 2016, DCB became available for the treatment of de novo small coronary lesions in Japan; however, there has been no multicenter analysis in a post-approval real-world clinical setting to date. The aim of this study was to evaluate the efficacy of DCB for de novo small coronary lesions based on a Japanese multicenter registry. From June 2016 to July 2017, a total of 111 lesions (102 patients) treated with DCB for de novo small coronary lesions were enrolled at six Japanese institutions. The primary endpoint was the rate of target lesion revascularization (TLR) at 12 months. Angiographic follow-up endpoints were binary restenosis and late lumen loss (LLL). Clinical follow-up data at 12 months were available for 106 lesions, excluding five lesions that required bailout stenting. The TLR rate was 5.7% (6/106 lesions). No cardiac death or target lesion thrombosis was observed. The binary restenosis rate was 14.4% and LLL was 0.0017 ± 0.37 mm. DCB angioplasty for de novo small coronary lesions in the real-world environment in Japan is effective with acceptable 12-month outcomes.

Efficacy and Safety of TurboHawk Plaque Rotation Combined With Drug-coated Balloon in Treating Diabetic Patients With Lower Extremity Arterial Disease.

To evaluate the efficacy and safety of TurboHawk plaque rotation system combined with drug-coated balloon in treating lower extremity arterial disease (LEAD) of diabetes patients, a total of 145 diabetic patients with LEAD from March 2015 to September 2016 were recruited in our study. Lower extremity arterial disease was diagnosed by ultrasound and CT angiography (CTA). According to the surgical method, 65 cases underwent TurboHawk plaque rotation combined with drug-coated balloon (group A), 80 cases underwent simple drug-coated balloon expansion (group B). The characteristics of lesion, function test, ankle-brachial index (ABI), and postoperative complications were analyzed. All the patients were followed up at 1, 3, 6, 12, and 24 months after operation. At baseline, there was no difference in all the characteristics between the 2 groups. The early postoperation minimum lumen diameter (MLD), lumen stenosis rate, and ABI in 2 groups both improved. As the follow-up time increased, patients in group A had significantly higher MLD and ABL value, as well as lower level of lumen stenosis rate, restenosis rate, late lumen loss, and target lesion revascularization (all P < .05). Accordingly, functional testing revealed the 6-minute walk distance, 6-minute claudication distance, resting ABI, and post-exercise ABI in group A were significantly higher than those in group B (all P < .05). Besides, major graft reintervention (4.62% vs 11.25%) and major adverse limb events (6.15% vs 12.5%) in group A occurred less frequently than group B (all P < .05). In conclusion, the long-term effect of the combined approach was better than only drug-coated balloon in LEAD in Chinese diabetes patients.

Randomized Comparison of Ridaforolimus-Eluting and Zotarolimus-Eluting Coronary Stents: 2-Year Clinical Outcomes From the BIONICS and NIREUS Trials

ObjectivesThis study sought to determine clinical outcomes between treatment groups over long-term follow-up. BackgroundThe safety and efficacy of a ridaforolimus-eluting stent (RES) was evaluated in the BIONICS (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis) and NIREUS (BioNIR Ridaforolimus Eluting Coronary Stent System [BioNIR] European Angiography Study) trials, demonstrating noninferiority of RES in comparison with a zotarolimus-eluting stent (ZES) regarding 1-year target lesion failure (TLF) and 6-month angiographic late lumen loss, respectively. MethodsPatient-level data from the BIONICS (N = 1,919) and NIREUS (N = 302) randomized trials were pooled, and outcomes in patients implanted with RES and ZES compared. Broad inclusion criteria allowed enrollment of patients with acute coronary syndromes and complex lesions. The primary endpoint was the 2-year rate of TLF or clinically driven target lesion revascularization. ResultsA total of 2,221 patients (age 63.2 ± 10.3 years; 79.7% men) undergoing percutaneous coronary intervention with RES (n = 1,159) or ZES (n = 1,062) were included. Clinical and angiographic characteristics were similar between groups. At 2 years, the primary endpoint of TLF was similar among patients implanted with RES and ZES (7.0% vs. 7.2%; p = 0.94). Rates of target lesion revascularization (4.8% RES vs. 4.1% ZES; p = 0.41) and target vessel–related myocardial infarction (3.1% RES vs. 3.8% ZES; p = 0.52) did not differ between groups. The overall rate of stent thrombosis was also similar (0.5% RES vs. 0.9% ZES; p = 0.39). ConclusionsIn a pooled analysis of 2 randomized trials, 2-year clinical outcomes were similar between patients undergoing percutaneous coronary intervention with RES and ZES. These results support the long-term safety and efficacy of RES for the treatment of a broad population of patients with coronary artery disease.

First-in-man randomised comparison of the Angiolite durable fluoroacrylate polymer-based sirolimus-eluting stent versus a durable fluoropolymer-based everolimus-eluting stent in patients with coronary artery disease: the ANGIOLITE trial.

The durable fluoroacrylate polymer-based sirolimus-eluting stent (Angiolite SES) has shown promising preclinical and clinical results regarding inflammatory vascular reaction and neointimal healing. We aimed to compare performance between the Angiolite SES and an everolimus-eluting stent (EES) in patients with coronary artery disease. The ANGIOLITE trial, a prospective, randomised, multicentre trial, compared the restenosis parameters of both stents in de novo coronary lesions. The primary endpoint was late lumen loss at six-month angiographic follow-up. In-stent healing was assessed by optical coherence tomography (OCT). The main clinical endpoint was target lesion failure (TLF) evaluated up to 24 months. A total of 223 patients were randomised 1:1 to EES or SES. At six months, in-stent late lumen loss was 0.08 mm (±0.38) for EES vs 0.04 mm (±0.39) for SES (difference=-0.04 mm, 95% CI: -0.15, 0.07, p for non-inferiority=0.002). By OCT, the rate of uncovered to total number of struts score >30% was comparable between the groups whereas neointimal thickness was reduced in the SES arm (9.0% [7.6, 10.6] vs 9.9% [8.5, 11.3], p=0.41; and 86.4 [81.6, 91.2] µm vs 72.1 [68.2, 76.0] µm, p<0.01, respectively). At 24 months, TLF occurred in eight patients (7.6% [3.3, 14.5]) in the EES arm and in seven patients (7.1% [2.9, 14.0]) in the SES arm (p=0.88). The definite/probable stent thrombosis rate was comparable between the groups (1.9% [0.2, 6.7] vs 1.0% [0.0, 5.5] EES vs SES, respectively; p=0.59). This trial demonstrates similar antirestenotic efficacy at midterm follow-up of the Angiolite SES vs an EES. Clinical endpoints were comparable between the groups at two-year follow-up. Visual summary. Main results of the ANGIOLITE trial.

Five-year clinical outcome of multicenter randomized trial comparing amphilimus - with paclitaxel-eluting stents in de novo native coronary artery lesions

ObjectivesLong-term data from randomized studies on polymer-free stents are scarce. Long-term data of Cre8 amphilimus eluting stent are still not available. We sought to investigate contribution of a polymer-free design versus a permanent-polymer one on the long-term. Methods and resultsPatients undergoing percutaneous coronary intervention for de novo lesions were randomized 1:1 to Cre8 or Taxus Liberté (323 overall, 126 Cre8). Original primary endpoint (6-month angiographic in-stent late lumen loss) already demonstrated the superiority of Cre8 vs Taxus (0.14 + 0.36 mm vs. 0.34 + 0.40 mm; p < 0.001). Secondary endpoints were the device oriented composite endpoint (DOCE), patient oriented composite endpoint (POCE) up to 5-year. Long-term follow-up data confirmed the superiority shown by Cre8 in the analysis of the angiographic endpoint at 6-month, especially in the diabetic patients, where the device strongly reduced the clinical difference with non-diabetic. Landmark analysis demonstrated that the incidence of DOCE after 1-year and up to 5-year follow up was significantly lower in patients implanted with Cre8 AES (2.1% Cre8 vs. 9.3% Taxus, p = 0.009). While no differences were found in terms of DOCE rate among diabetic and non-diabetic patients treated with the Cre8 AES (HR 1.039; 95%CI 0.320–3.374), this was not true for Taxus (HR 2.64; 95%CI 1.112–6.278). ConclusionsCre8 showed favourable safety and efficacy results versus Taxus at 5-years follow-up, with a superior clinical performance for the DOCE endpoint from 1 to 5 years. Cre8, differently from Taxus, has been able to strongly reduce the differences in clinical outcome between diabetic and non-diabetic up to 5 years, suggesting the higher efficacy of Cre8 in the treatment of diabetic patients.

Long-term clinical safety and efficacy of drug-coated balloon in the treatment of in-stent restenosis: A meta-analysis and systematic review.

The aim of this study was to evaluate the long-term clinical safety and efficacy of drug-coated balloon (DCB) in the treatment of in-stent restenosis (ISR). There is a long-term safety issue in peripheral arterial disease patients treated with paclitaxel-coated balloon, this has also raised concerns on DCB in coronary intervention. Nine randomized controlled trials (RCTs) and nine observational studies (OSs) were included with a total of 3,782 patients (1,827 in the DCB group, 1,955 in the drug-eluting stent [DES] group) being analyzed. The primary outcome measure-major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac death (CD), stent thrombosis (ST), all-cause death (AD), and coronary angiography outcomes included late lumen loss (LLL), minimum luminal diameter (MLD), diameter stenosis (DS) were analyzed. DCB treatment significantly reduced the LLL (MD: -0.13; [CI -0.23 to -0.03], p = .01). No difference was found for MLD (MD: -0.1; [CI -0.24 to 0.04], p = .17) and DS% (RR = 0.98 [CI 0.80-1.20], p = .86). There was no significant difference in TLR, TVR, MI, CD, ST, AD, and the overall incidence of MACEs between the two groups up to 3 years follow-up. Subgroup analysis for different type of ISR and DES showed no significant difference in the incidence of endpoints, and there is no difference when considering RCTs or OSs only. The safety and efficacy of the DCB and DES in the treatment of ISR is comparable at up to 3 years follow-up.

Role of optical coherence tomography for distal left main stem angioplasty.

The objective is to analyze the acute and midterm angiographic outcome of percutaneous treatment of left main coronary stem (LM-PCI) guided by optical coherence tomography (OCT). LM-PCI is a complex procedure, and several anatomical factors may impair its outcome. Intravascular imaging is emerging as a useful tool to guide the procedure. We conducted a retrospective analysis of patients undergoing LM-PCI at three European centers between 2014 and 2017 with a control angiography at 6-12 months. Patients were divided into two groups: OCT-guidance (pre- and post-PCI) and control group (standard angiographic guidance with/out intravascular ultrasound [IVUS]). A blinded core lab analyzed all angiographic images. Primary endpoint was late lumen loss (LLL) after 6 months. A total of 112 patients entered the study, 55 in the OCT group and 57 in the control group (10 IVUS). Baseline and procedural characteristics were similar between groups. Overall, reference vessel diameter of the LM was 3.98 ± 0.65 mm. OCT guidance detected four cases of stent underexpansion (7.2%) and six cases of acute malapposition (10.9%). After a median of 207 ± 23 days, LLL of LM tended to be lower in the OCT group (0.12 ± 0.41 vs. 0.26 ± 0.52 mm, p = .10), and was significantly reduced in the distal portion of the main vessel (0.03 ± 0.45 vs. 0.24 ± 0.53 mm, p = .025). Percent diameter stenosis was also lower (14 ± 9 vs. 19 ± 16%, p = .05). Adverse event rates were similar in the two groups. In this study, systematic OCT guidance during LM-PCI allowed a timely detection and correction of acute stent underexpansion and malapposition, and was associated with signs of improved angiographic outcome at midterm, compared to standard practice.

122Mechanism and impact of lesion morphology on the late lumen loss of drug-eluting resorbable magnesium scaffolds: a serial optical coherence tomography study

Abstract Introduction Resorbable Magnesium Scaffolds have demonstrated favourable clinical results with acceptable late lumen loss (LLL). However, the pathomechanisms influencing LLL of resorbable sirolimus-eluting metallic scaffold (Magmaris) have not been analyzed. Purpose Using serial optical coherence tomography (OCT), we investigated potential factors, i.e. the contribution of recoil versus neointimal hyperplasia (NIH). Methods Patients who were enrolled into BIOSOLVE-II, and underwent serial angiography and OCT (baseline and follow-up: 6-month and/or 1-year) were analyzed. Patients were divided into 2 groups based on angiographic in-scaffold LLL &lt;0.5mm or ≥0.5mm. Endpoints were late absolute recoil and NIH area as assessed by OCT. Results A total of 70 patients (LLL &lt;0.5mm: n=41, LLL ≥0.5mm: n=29) were serially analyzed. Patient and lesion characteristics were comparable and there was no significant difference in mean and minimal scaffold area between groups at baseline. Late absolute recoil was significantly smaller among patients with LLL &lt;0.5mm (0.53±0.68 mm2) compared with those with LLL ≥0.5mm (1.48±1.20 mm2, P&lt;0.001) (Figure). A small difference in NIH area at follow-up was observed (LLL &lt;0.5mm: 1.47±0.33 mm2 vs. LLL ≥0.5mm: 1.68±0.34 mm2, P=0.013). In a matched-frame analysis (baseline and follow-up), late absolute recoil varied according to the underlying plaque type (lipid: 0.63±1.23 mm2, calcified: 0.81±1.44 mm2, and fibrous: 1.20±1.52 mm2, P&lt;0.001), while there was no difference with regards to NIH area (P=0.132). Conclusion The main driver of late lumen loss of sirolimus-eluting absorbable metal scaffold was late scaffold recoil, while the contribution of NIH was modest. The degree of late scaffold recoil depended on the underlying plaque type and was highest among fibrotic lesions. Future studies will address the impact of procedural factors such as adequate lesion preparation and post-dilatation. Acknowledgement/Funding Biotronik

P954Value of a single bolus erythopoetin in STEMI patients treated with the Genous endothelial progenitor cell capture stent

Abstract Background The Endothelial Progenitor Cell (EPC) stent was designed to capture circulating EPCs and promote early stent re-endothelization. Erythropoietin (EPO) stimulates mobilization of EPC from the bone marrow. Combination of EPO and the EPC stent in the setting of ST-segment elevation myocardial infarction (STEMI) has never been investigated. Methods STEMI patients enrolled in the HEBE-III trial were randomized to a single bolus of EPO or No-EPO after implantation of the EPC capture stent. Late lumen loss (LLL) was determined at 9-month angiographic follow-up. Clinical data was collected at 30 days and 12 months. Results 196 patients were randomized to EPO (n=100) or No-EPO (n=96). No significant difference in baseline characteristics was observed between the two groups. A significant reduction in angiographic LLL was observed with EPO (0.43±0.57mm) as compared to No-EPO (0.74±0.63mm) (p=0.011). At 12 months follow up, no difference with regard to death or re- infarction was observed in both groups, whereas significant reduction in the need for target vessel revacularization for the EPO versus No-EPO was observed with rates of 7.1% and 19.1% respectively (p=0.013). Angiographic and clinical results EPO (n=39) No-EPO (n=45) P-value Angiography Lume late loss 0.43±0.57 0.74±0.63 0.011 12 months clinical Death 0 0 ns Re infarction 0 1 (2.2%) ns Additional PCI 4 (10.3%) 17 (37.8%) 0.004 CABG 2 (5.1%) 2 (4.4%) ns CVA 0 0 ns Bleeding 3 (7.7%) 4 (8.9%) ns ns = not significant; CVA = cerebrovascular accident; CABG = coronary bypass graft; PCI = percutaneous coronary intervention. Conclusion In STEMI patients treated with EPC capture stent, additional EPO can further improve angiographic LLL

P5615A randomised study comparing FFR-guided paclitaxel-coated balloon angioplasty vs. drug-eluting bioresorbable scaffolds with 9 months invasive follow-up

Abstract Background Elimination of a permanent metallic stent from standard PCI techniques is desirable since mid- and longterm adverse reactions are attributed to an intracoronary foreign body. Purpose To investigate two “metal-free” PCI techniques using either drug-coated balloons (DCB) or bioresorbable scaffolds (BRS) in stable coronary artery disease regarding their safety and efficacy (NCT02607241) and clinical course. Methods 59 patients (table 1) were prospectively randomized for elective PCI of de novo stenosis with either BRS implantation (N=28) or with DCB only angioplasty (N=31). The DCB only arm was treated by a previously implemented protocol including sequential balloon predilations and repetitive FFR (fractional flow reserve) measurements. Stenting was deferred if FFR was &gt;0.80 and in the absence of flow-limiting dissections after final DCB dilatation. All BRS were post-dilated using a non-compliant balloon. All BVS were post-dilated (non-compliant balloon). Optical coherence tomography (OCT) was performed during index procedure and at 9-month f/u. Results Both groups were well balanced without significant differences in clinical characteristics (table 1). Procedural success was achieved in 89.3% in the BRS and 77.4% in the DCB group. Parameter of quantitative coronary angiography are shown in the table 2. The predefined primary end point (efficacy) net luminal gain was significantly larger in the DCB group (noninferiority t-Test, margin: 0.2mm, 80% power). Accordingly, the secondary endpoint late lumen loss indicated with −0.20±0.73 vessel enlargement at the stenotic site in the DCB group at 9-month f/u. Target lesion failure during 9-month f/u occurred much more in the BRS group (14.3% (N=4) vs. 3.2% (N=1), p=0.180) but did not reach significance in this small sample size. In detail, there were 2 scaffold thrombosis despite OCT-guided index procedure in the BRS group with subsequent myocardial infarction, and 2 restenosis in the BRS vs. 1 restenosis in the DCB group requiring repeat target lesion revascularization. Due to safety concerns of BRS and the worldwide recall of Absorb BRS the study was prematurely terminated. Conclusion Our data add evidence for FFR-guided “DCB only” PCI as an attractive, safe and feasible alternative by showing a favorable longterm course contrary to the late lumen loss of conventional coronary stents. The Absorb BRS is potentially harmful with a high percentage of target lesion failure including scaffold thrombosis despite OCT-guided implantation and should be avoided.

Prevention of neointimal formation after angioplasty using tetramethylpyrazine-coated balloon catheters in a rabbit iliac artery model.

Restenosis remains a clinical problem; drug-coated balloons (DCBs) have demonstrated high efficiency in this situation. DCBs prevent neointimal hyperplasia by inhibiting cell proliferation and migration. Tetramethylpyrazine (TMP) is a traditional Chinese medicine originally isolated from the rhizome of Ligusticum Walliichii, which can inhibit platelet aggregation and smooth muscle cell proliferation. We hypothesized that TMP-coated balloons (TCB) could reduce neointimal hyperplasia through the NF-κB signalling pathway. Twenty-one New-Zealand White rabbits (2.5-3.0 kg, male) were fed high-fat diets; 36 bilateral iliac artery stenosis models were successfully established by balloon straining. Rabbits were randomly treated with TCB (n=20) or plain balloons (PBA, n=16) (3 died during model construction). Angiographies were recorded at baseline, the immediate period, and 4 weeks later. Animals were euthanized and arteries collected for histological analysis and immunohistochemical staining. Protein expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 of the vessel samples were analyzed using Western blotting. No difference existed in the baseline lesion characteristics or procedural results. Angiographic follow-up was successfully performed on 18 rabbits (TCB: n=20, PBA: n=16), except for 3 deaths related to the operation. Treatment with TCB was superior to that with PBA, with lower late lumen loss (0.45±0.23 vs. 0.84±0.17 mm, P<0.01). Pathological analysis confirmed the efficiency of TCB through decreasing the area stenosis rate compared with PBA (46.48%±8.22% vs. 75.24%±6.10%, P<0.01). As determined by Western blotting, significant reductions occurred in PCNA and NF-κB p65 protein intensity in the TCB group versus the PBA group (all P<0.01). TCB efficiently mitigated restenosis in the rabbit iliac artery model. This study elucidated that TCB could restrain intimal hyperplasia of vessels by inhibiting the activation of the NF-κB pathway to reduce inflammatory response and decrease the rate of cell proliferation through suppressing PCNA expression.