Mean Neointimal Area Research Articles

Safety and performance of the third-generation drug-eluting resorbable coronary magnesium scaffold system in the treatment of subjects with de novo coronary artery lesions: 6-month results of the prospective, multicenter BIOMAG-I first-in-human study.

A third-generation coronary drug-eluting resorbable magnesium scaffold (DREAMS 3G) was developed to enhance the performance of previous scaffold generations and achieve angiographic outcomes comparable to those of contemporary drug-eluting stents. This prospective, multicenter, non-randomized, first-in-human study was conducted at 14 centers in Europe. Eligible patients had stable or unstable angina, documented silent ischemia, or non-ST-elevation myocardial infarction, and a maximum of two single de novo lesions in two separate coronary arteries with a reference vessel diameter between 2.5mm and 4.2mm. Clinical follow-up was scheduled at one, six and 12 months and annually thereafter until five years. Invasive imaging assessments were scheduled six and 12 months postoperatively. The primary endpoint was angiographic in-scaffold late lumen loss at six months. This trial was registered at ClinicalTrials.gov (NCT04157153). Between April 2020 and February 2022, 116 patients with 117 coronary artery lesions were enrolled. At six months, in-scaffold late lumen loss was 0.21mm (SD 0.31). Intravascular ultrasound assessment showed preservation of the scaffold area (mean 7.59mm2 [SD 2.21] post-procedure vs 6.96mm2 [SD 2.48]) at six months) with a low mean neointimal area (0.02mm2 [SD 0.10]). Optical coherence tomography revealed that struts were embedded in the vessel wall and were already hardly discernible at six months. Target lesion failure occurred in one (0.9%) patient; a clinically driven target lesion revascularization was performed on post-procedure day 166. No definite or probable scaffold thrombosis or myocardial infarction was observed. These findings show that the implantation of DREAMS 3G in de novo coronary lesions is associated with favorable safety and performance outcomes, comparable to contemporary drug-eluting stents. This study was funded by BIOTRONIK AG.

Randomized comparison of 9-month stent strut coverage of biolimus and everolimus drug-eluting stents assessed by optical coherence tomography in patients with ST-segment elevation myocardial infarction. Long-term (5-years) clinical follow-up (ROBUST trial).

The aim of the study was to compare healing (assessed by optical coherence tomography [OCT]) of biolimus A9 (BES) and everolimus drug-eluting stents (EES) at 9-month follow-up in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). Nine-month clinical and angiographic data were also compared in both groups as well as clinical data at 5 years of follow-up. A total of 201 patients with STEMI were enrolled in the study and randomized either to pPCI with BES or EES implantation. All patients were scheduled for 9 months of angiographic and OCT follow-up. The rate of major adverse cardiovascular events (MACE) was comparable at 9 months in both groups (5% in BES vs. 6% in the EES group; p = 0.87). Angiographic data were also comparable between both groups. The main finding at 9-month OCT analysis was the greatly reduced extent of mean neointimal area at the cost of a higher proportion of uncovered struts in the BES group (1.3 mm² vs. 0.9 mm²; p = 0.0001 and 15.9% vs. 7.0%; p = 0.0001, respectively). At 5 years of clinical follow-up the rate of MACE was comparable between both groups (16.8% vs. 14.0%, p = 0.74). The study demonstrates a very low rate of MACE and good 9-month stent strut coverage of second-generation BES and EES in patients with STEMI. BES showed greatly reduced extent of mean neointimal hyperplasia area at the cost of a higher proportion of uncovered struts when compared to EES. The rate of MACE was low and comparable in both groups at 5 years.

Drug-eluting, balloon-expandable, bioresorbable vascular scaffolds reduce neointimal thickness and stenosis in an animal model of percutaneous peripheral intervention

ObjectiveRecanalization with balloon angioplasty and/or self-expanding stents (SES) has become the endovascular treatment of choice for symptomatic femoropopliteal occlusive disease. These strategies generate suboptimal clinical results, however, because they fail to expand the artery fully and ineffectively prevent recoil, neointimal hyperplasia, and restenosis. Balloon-expandable stents, given their greater radial force and rigid structure, represent a more effective treatment strategy, but only short lengths can be implanted safely in arteries that deform and bend with skeletal motion. The purpose of this preclinical experiment was to test the hypothesis that simultaneous implantation of a series of short, resorbable, balloon-expandable, paclitaxel-eluting scaffolds would prevent neointimal hyperplasia and stenosis compared with SES in an animal model of percutaneous femoropopliteal intervention. MethodsWe extruded 6 × 60 mm Efemoral Vascular Scaffold Systems (EVSS) from copolymers of poly-L-lactic acid, coated with paclitaxel 3 μg/mm2, crimped onto a single delivery balloon, and implanted percutaneously into the iliofemoral arteries of eight Yucatan mini-swine. We implanted 7- to 8-mm × 60 mm SES into the contralateral experimental arteries. The animals were serially imaged with contrast angiography and optical coherence tomography after 30, 90, 180, 365, and 730 days. The primary end point of this study was neointimal morphometry over time. Secondary end points included acute deformation and angiographic and optical coherence tomography-derived measurements of chronic vascular response. ResultsOver the 2-year study period, one SES was found to be completely occluded at 90 days; all EVSS were widely patent at all time points. Arteries treated with SES exhibited profound neointimal hyperplasia with in-stent stenosis. In contrast, arteries treated with EVSS exhibited only modest vascular responses and minimal stenosis. After 2 years, the mean neointimal thickness (0.45 ± 0.12 vs 1.31 ± 0.91 mm; P < .05) and area (8.41 ± 3.35 vs 21.86 ± 7.37 mm2; P < .05) were significantly decreased after EVSS implantation. By 2 years, all scaffolds in all EVSS-treated arteries had resorbed fully. ConclusionsIn this preclinical animal model of peripheral endovascular intervention, the EVSS decreased neointimal hyperplasia and stenosis significantly compared with SES, then dissolved completely between the first and second years after implantation.

Vascular healing in high-bleeding-risk patients at 3-month after everolimus-eluting stent versus biolimus A9-coated stent implantation: insights from analysis of optical coherence tomography and coronary angioscopy.

The prevalence of high-bleeding-risk (HBR) patients who undergo coronary stenting has been reported as 20-40%. This study sought to assess vascular healing in HBR patients by coronary angioscopy (CAS) and optical coherence tomography (OCT). We prospectively analyzed 38 HBR patients with coronary artery disease who successfully underwent everolimus-eluting stent (EES) implantation (20 patients, 23 lesions) or drug-coated stent (DCS) implantation (18 patients, 18 lesions). Follow-up coronary angiography, CAS, and OCT were planned at 3months after the procedure. The clinical characteristics and inclusion criteria of HBR were comparable between groups. CAS analysis showed that mean yellow color grade was significantly higher with EES than with DCS (1.33 [1.0, 1.67] vs. 1.0 [0.67, 1.5]; P = 0.04). In contrast, OCT analysis demonstrated that most struts in both groups were well-apposed struts with neointimal coverage (93.9% each; P = 1.00), and percentages of the mean neointimal area were comparable between EES and DCS (4.4 ± 3.5mm2 vs. 4.5 ± 4.1mm2; P = 0.91). The frequency of uncovered struts was significantly lower with EES than with DCS (2.4% vs. 5.3%; P < 0.001), whereas the frequency of malapposed struts was significantly higher with EES than with DCS (3.5% vs. 0.8%; P < 0.001). During follow-up, no stent thrombosis or major bleeding complications were encountered in either group. Among HBR patients, both EES and DCS demonstrated good vascular healing at 3-month follow-up with some different features in CAS and OCT assessments.

Optical coherence tomography tissue coverage and characterization at six months after implantation of bioresorbable scaffolds versus conventional everolimus eluting stents in the ISAR-Absorb MI trial

PurposeData regarding vessel healing by optical coherence tomography (OCT) after everolimus-eluting bioresorbable scaffolds (BRS) or everolimus-eluting metallic stent (EES) implantation in acute myocardial infarction (AMI) patients is scarce. We compared OCT findings after BRS or EES implantation in patients with AMI enrolled in a randomized trial.MethodsIn ISAR-Absorb MI, AMI patients were randomized to BRS or EES implantation, with 6–8 month angiographic follow-up. This analysis includes patients who underwent OCT during surveillance angiography. Tissue characterization was done using grey-scale signal intensity analysis. The association between OCT findings and target lesion failure (TLF) at 2 years was investigated.ResultsOCT was analyzed in 103 patients (2237 frames, 19,827 struts) at a median of 216 days post-implantation. Of these, 70 were treated with BRS versus 32 with EES. Pre-(92.8 vs. 68.7%, p = 0.002) and post-dilation (51.4 vs. 12.5%, p < 0.001) were more common in BRS as compared to EES. Strut coverage was higher in BRS vs. EES (97.5% vs. 90.9%, p < 0.001). Mean neointimal thickness was comparable in both groups [85.5 (61.9, 124.1) vs. 69.5 (32.7, 127.5) µm, respectively, p = 0.20]. Mature neointimal regions were numerically more common in BRS (43.0% vs. 24.6%; p = 0.35); this difference was statistically significant in ST-elevation myocardial infarction patients (40.9% vs. 21.1%, p = 0.03).At two-years, 8 (7.8%) patients experienced TLF. Mean neointimal area [0.61 (0.21, 1.33) vs. 0.41 (0.11, 0.75) mm2, p = 0.03] and mean neointimal coverage [106.1 (65.2, 214.8) vs. 80.5 (53.5, 122.1) µm, p < 0.01] were higher, with comparable tissue maturity, in lesions with versus without TLF.ConclusionsIn selected patients who underwent OCT surveillance 6–8 months after coronary intervention for AMI with differing implantation characteristics depending on the device type used, vessel healing was more advanced in BRS compared with EES, particularly in the STEMI subgroup.

P5613Proportional relationship between early mobilization of bone marrow progenitor cells and the extent of vascular injury during coronary stenting: insights on the role of systemic mechanisms of vascular

Abstract Background The role of circulating progenitor cells (CPCs) on vascular repair after everolimus-eluting stent (EES) implantation is largely unknown. Objectives The aim of the study was to investigate the quantitative and temporal variations of CPCs levels after EES implantation, and its relationship with the degree of peri-procedural vascular damage, stent healing and neointimal hyperplasia, as measured by optical coherence tomography (OCT). Methods In a consecutive series of patients with stable coronary artery disease undergoing stent implantation CPC subpopulations (CD34+/CD45low, CD133+/CD45low, CD34/KDR/CD45low, CD133/KDR/CD45low) were evaluated using a flow cytometry technique at baseline, 1 and 4 weeks. OCT evaluation was performed immediately after stent implantation to quantify stenting-related injury, and at 9-month follow-up to assess mid-term vascular response. Results Twenty patients (mean age 66±9 years; 80%male) with 24 stenoses treated with EES were included in the study. Vascular injury score was associated with the increase of CD133+/KDR/CD45 low at 1-week (β0.28 [95% CI0.15; 0.41], p&lt;0.001) and with the maximum neointimal thickness at 9-month follow-up (β0.008 [95% CI-0.0004; 0.002]:p=0.04). Mean neointimal area at 9-month was associated with the increase in the number of CD34+/CD45low at 1 week (β0.029 [95% CI0.025;-0.033]; p&lt;0.0001). Inverse relationships between the number of uncoated and apposed struts at 9-month and the 1-week delta values of CD34/KDR/CD45low and CD133/KDR/CD45low (β-4.49 [95% CI-8.17;-0.82]; p=0.017 and β −12.53 [95% CI: −22.17; −2.90]; p=0.011, respectively) were also found. Conclusion Long-term vascular healing after EES implantation is modulated by early changes in levels of CPC subpopulations. This systemic response is proportional to the extent of vessel wall injury. Early mobilization of CPCs influences mid-term strut coverage and the development of neointimal hyperplasia. Acknowledgement/Funding Dr Jimenez-Quevedo is a recipient of the ISCIII (Instituto de Salud Carlos III) grant “Fondo de Investigaciόn Sanitaria” (PI11/00299) to perform this

Bioresorbable vascular scaffolds in coronary chronic total occlusions: clinical, vasomotor and optical coherence tomography findings at three-year follow-up (ABSORB-CTO study).

Percutaneous treatment of coronary chronic total occlusion (CTO) is associated with important arterial remodelling after successful recanalisation. Bioresorbable vascular scaffold (BVS) implantation in CTO has been shown to be feasible and can be of interest when the scaffold achieves complete bioresorption. We sought to evaluate the three-year results in terms of clinical events, serial imaging outcomes and vasomotion response in CTO lesions successfully treated with BVS. A total of 33 patients (35 CTO lesions) successfully treated with BVS were included in the ABSORB-CTO study. Clinical outcomes, quantitative coronary angiography (QCA) and optical coherence tomography (OCT) assessment were analysed at one- and three-year follow-up. Vasomotion examination was also performed at three years. At three years, cumulative target vessel reocclusion was observed in four lesions (11.4%). By QCA, the in-scaffold segment presented a lumen loss of 0.23±0.46 mm compared with the baseline procedure (p=0.001) and a lumen gain of 0.05±0.29 mm between one and three years (p=0.220). By OCT, the mean neointimal area stenosis progressed from 11.45% at 12 months to 17.10% at 36 months (p<0.001) and mean scaffold area increased continuously at 12 (+12%; p<0.001) and at 36 months (+14.85%; p=0.001). Late acquired incomplete scaffold apposition (LAISA) observed at 12 months in three patients was completely undetectable at three years. Most cases responded to endothelium-dependent vasomotor stimuli (69%). Vasoconstriction to acetylcholine was the predominant response (45%). Successful recanalisation of coronary CTO with BVS implantation is associated with favourable clinical and imaging outcomes. Despite vessel motility restoration, successfully treated CTOs remain with signs of endothelial dysfunction.

Impact of Combination Therapy with Ezetimibe/Simvastatin Treatment on the Neointimal Response to Biodegradable Polymer Biolimus-Eluting Stent Implantation in Patients with Acute Myocardial Infarction: Serial Assessment with Optical Coherence Tomography

The aim of this study was to compare the neointimal response at 12-month follow-up between ezetimibe/simvastatin (Vytorin, manufactured by Merck) 10/10 mg and Vytorin 10/40 mg after biodegradable polymer Biolimus-eluting stent (BP-BES) implantation in patients with acute myocardial infarction (AMI). A total of 20 patients requiring revascularization were randomly assigned to receive either Vytorin 10/10 mg (n = 9) or Vytorin 10/40 mg (n = 11). Baseline optical coherence tomography (OCT) was performed after stent implantation, and follow-up OCT was scheduled at 12 months. We performed follow-up OCT in 18 patients (Vytorin 10/10 mg (n = 9) or Vytorin 10/40 mg (n = 9)). A total of 842 frames and 8552 struts were analyzed at initial and follow-up OCT. At follow-up, the percentage of uncovered struts was not significantly different between both groups (6.61 ± 10.29% vs. 7.57 ± 6.45%, p = 0.815). The percentage of malapposed struts was also similar between both groups (0.69 ± 1.58% vs. 1.55 ± 2.72%, respectively, p = 0.422). Mean percent neointimal hyperplasia area was not significantly different between both groups (6.53 ± 3.26% vs. 6.37 ± 8.96%, p = 0.961). This OCT study showed that both high- and moderate-intensity dosing of Vytorin was associated with relatively lower percentages of uncovered struts and malapposed struts after Biolimus A9-eluting stent implantation in patients with AMI.

Uncertainty Quantification of a Multiscale Model for In-Stent Restenosis

PurposeCoronary artery stenosis, or abnormal narrowing, is a widespread and potentially fatal cardiac disease. After treatment by balloon angioplasty and stenting, restenosis may occur inside the stent due to excessive neointima formation. Simulations of in-stent restenosis can provide new insight into this process. However, uncertainties due to variability in patient-specific parameters must be taken into account.MethodsWe performed an uncertainty quantification (UQ) study on a complex two-dimensional in-stent restenosis model. We used a quasi-Monte Carlo method for UQ of the neointimal area, and the Sobol sensitivity analysis (SA) to estimate the proportions of aleatory and epistemic uncertainties and to determine the most important input parameters.ResultsWe observe approximately 30% uncertainty in the mean neointimal area as simulated by the model. Depending on whether a fast initial endothelium recovery occurs, the proportion of the model variance due to natural variability ranges from 15 to 35%. The endothelium regeneration time is identified as the most influential model parameter.ConclusionThe model output contains a moderate quantity of uncertainty, and the model precision can be increased by obtaining a more certain value on the endothelium regeneration time. We conclude that the quasi-Monte Carlo UQ and the Sobol SA are reliable methods for estimating uncertainties in the response of complicated multiscale cardiovascular models.

Mobilization of progenitor cells and assessment of vessel healing after second generation drug-eluting stenting by optical coherence tomography

BackgroundBone marrow-derived progenitor cells likely contribute to both endothelial- and smooth muscle cell-dependent healing responses in stent-injured vessel sites. This study aimed to assess mobilization of progenitor cells and vessel healing after zotarolimus-eluting (ZES) and everolimus-eluting (EES) stents. Methods and resultsIn 63 patients undergoing coronary stent implantation, we measured circulating CD34+CD133+CD45low cells and serum levels of biomarkers relevant to stem cell mobilization. In 31 patients of them, we assessed vessel healing within the stented segment using optical coherence tomography (OCT) imaging. The CD34+CD133+CD45low cells increased 68±59% 7days after bare metal stent (BMS), 10±53% after ZES (P<0.01 vs BMS), 3±49% after EES (P<0.001 vs BMS), compared with baseline. Percent change in CD34+CD133+CD45low cells was positively correlated with that in stromal cell-derived factor (SDF)-1α (R=0.29, P=0.034). Percentage of uncovered struts was higher in the EES group (14.4±17.3%), compared with the BMS (0.7±1.3, P<0.01) and ZES (0.4±0.5, P<0.01) groups. The change in CD34+CD133+CD45low cells showed positive correlation with OCT-quantified mean neointimal area (R=0.48, P<0.01). Finally, circulating mononuclear cells obtained from 5 healthy volunteers were isolated to determine the effect of sirolimus, zotarolimus and everolimus on vascular cell differentiation. The differentiation of mononuclear cells into endothelial-like cells was dose-dependently suppressed by sirolimus, zotarolimus, and everolimus. ConclusionsMobilization of progenitor cells was suppressed, and differentiation of mononuclear cells into endothelial-like cells was inhibited, in association with increased number of uncovered stent struts, even after second generation drug-eluting stenting. These data suggest that new approaches are necessary to enhance stent healing.

Effects of angiotensin receptor blockers on neointimal characteristics in angina patients requiring stent implantation: optical coherence tomography analysis

BackgroundAngiotensin receptor blockers (ARBs) are known for its anti-inflammatory and anti-proliferative effects. The aim of the study was to evaluate long-term effects of ARBs on morphologic characteristics of stent restenosis in patients with coronary artery disease requiring stent implantation by optical coherence tomography (OCT).MethodsPatients with coronary artery disease having history of drug-eluting stent implantation (n = 407) were analyzed on the basis of ARB therapy as the ARB group (n = 162) and the non-ARB group (n = 245). Neointimal characterizations were performed at lesions with diameter stenosis >30% with OCT in each group. Major adverse cardiovascular events (MACEs), lumen area, stent area, neointimal area, neointimal thickness, nonapposed struts, uncovered struts, and intraluminal mass between two groups were also observed.ResultsMore patients in the ARB group revealed homogeneous and layered neointimal pattern (44.9% vs. 35.6%, P < 0.001, and 16.8% vs. 10.6%, P < 0.001, respectively), and whereas patients in the non-ARB group revealed heterogeneous neointimal pattern (1.1% vs. 7.6%, P < 0.001). Mean neointimal area (1.09 ± 1.00 mm2 vs. 1.38 ± 1.24 mm2) and mean neointimal thickness (140.6 ± 112.0 μm vs. 189.6 ± 423.1 μm) with OCT were smaller in the ARB group when compared to the non-ARB group. Percentage of covered stents was significantly higher in the ARB group when compared to the Non-ARB group (97.3% vs. 92.6%, P = 0.015). Other factors such as follow-up % diameter stenosis, late lumen loss, binary restenosis, MACEs, various neointimal characteristics analyzed by image analyzing software did not show significant differences.ConclusionThe use of ARBs after drug-eluting stent implantation demonstrated difference in neointimal characteristics, less amount of neointimal area and fewer number of uncovered stent struts during the follow-up OCT, indicating the anti-proliferative and anti-inflammatory effects of ARBs.

In-stent fractional flow reserve variations and related optical coherence tomography findings: the FFR-OCT co-registration study.

We sought to assess in-stent variations in fractional flow reserve (FFR) in patients with previous percutaneous coronary intervention (PCI) and to associate any drop in FFR with findings by optical coherence tomography (OCT) imaging. Suboptimal post-PCI FFR values were previously associated with poor outcomes. It is not known to which extent in-stent pressure loss contributes to reduced FFR. In this single-arm observational study, 26 patients who previously underwent PCI with drug-eluting stent or scaffold implantation were enrolled. Motorized FFR pullback during continuous intravenous adenosine infusion and OCT assessments was performed. Post-PCI FFR < 0.94 was defined as suboptimal. At a median of 63 days after PCI (interquartile range: 59-64days), 18 out of 26 patients (72%) had suboptimal FFR. The in-stent drop in FFR was significantly higher in patients with suboptimal FFR vs. patients with optimal FFR (0.08 ± 0.07 vs. 0.01 ± 0.02, p < 0.001). Receiver operating characteristic curve analysis showed that an in-stent FFR variation of > 0.03 was associated with suboptimal FFR. In patients with suboptimal FFR, the OCT analyses revealed higher mean neointimal area (respectively: 1.06 ± 0.80 vs. 0.51 ± 0.23 mm2; p = 0.018) and higher neointimal thickness of covered struts (respectively 0.11 ± 0.07 vs. 0.06 ± 0.01mm; p = 0.021). Suboptimal FFR values following stent-implantation are mainly caused by significant in-stent pressure loss during hyperemia. This finding is associated to a larger neointimal proliferation.

Analysis of optical coherence tomography of early and very late stent restenosis after drug-eluting stent implantation

Objective: Using optical coherence tomography (OCT) to analyze the morphological characteristics of lesions between early in-stent restenosis (E-ISR) and very late in-stent restenosis (VL-ISR) after drug-eluting stents (DES) implantation. Methods: In 25 patients (DES) with ISR, OCT images were acquired before percutaneous coronary intervention (PCI), the morphological characteristics of E-ISR (<1 years, n=14) and VL-ISR (>3 years, n=11) were compared.The quantitative and qualitative analysis of the entire stent and the minimum lumen area (MLA) site were carried out respectively. OCT quantitative restenotic tissue analysis included the assessment of mean lumen area, mean stent area, mean neointimal area and mean neointimal burden.OCT qualitative restenotic tissue analysis included the assessment of tissue structure [homogeneous or heterogeneous intima (lipid-rich neoitima, thin-cap fibroatheroma (TCFA)-like intima)], presence of microvessels, intraluminal material (red thrombus, pale thrombus), disrupted intima with cavity and tissue prolapse and was performed at every 1-mm slice of the entire stent. Results: Compared with the E-ISR group, the proportion of cross-sections with heterogeneous intima in the entire stent was significantly higher in the VL-ISR group (60.57% vs 32.93%, P=0.005), and both peristent and intraintimal microvessels were more frequently observed in the VL-ISR group (P<0.05). In addition, lipid-rich neointima (72.7% vs 21.4%, P=0.017), TCFA-like intima (54.5% vs 7.1%, P=0.021), disrupted intima with visible cavity (63.6% vs 7.1%, P=0.007) and red thrombus (63.6% vs 7.1%, P=0.007) were observed more frequently in the VL-ISR group compared with E-ISR group for the entire stent.The heterogeneous intima was observed more frequently in the VL-ISR group (90.9% vs 35.7%, P=0.012) at the MLA sites.Intraintimal microvessels and disrupted intima with visible cavity were observed only in the VL-ISR group. Conclusions: OCT imaging indicates that the morphological characteristics of restenosis lesions in VL-ISR are different from those in E-ISR.The atherosclerotic changes of neointima, such as lipid-rich neointima, disrupted intima with cavity and microvessels are more often observed in VL-ISR lesions after DES implantation compared with E-ISR.Progression of the atherosclerosis within neointima after DES implantation may be associated with VL-ISR.

Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model

BackgroundSeveral investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model. MethodsA total of 30 pigs were randomly allocated based on the following P2Y12 inhibitor: (1) clopidogrel 300mg loading plus 75mg maintenance (n=10); (2) prasugrel 60mg loading plus 10mg maintenance (n=10); (3) ticagrelor 180mg loading plus 180mg maintenance (n=10). In each group, zotarolimus-eluting stents were implanted in the proximal portion of the left anterior descending artery and left circumflex artery. One month after stenting, the animals underwent follow-up angiography, endothelial function assessment, optical coherence tomography (OCT) and histopathological analysis. ResultsRegarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups. ConclusionsCompared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation.

Angiographic, optical coherence tomography and histology findings from combination of a drug-coated balloon with an everolimus-eluting stent in a porcine model

BackgroundWe designed a porcine model to compare the angiographic, optical coherence tomography (OCT) and histological findings of implanting an everolimus-eluting stent (EES) in the same segment of the coronary artery pre-treated with a drug-coating balloon (DCB; paccocath as carrier) with EES alone and DCB plus a bare metal stent (BMS). MethodsSeven female swine averaging 46.0±2.4kg were treated by random assignment as follows: DCB followed by EES; DCB followed by BMS; and EES alone. Quantitative coronary angiography (QCA) and OCT were carried out post-implantation and repeated after 28±1days. ResultsAll arteries remained patent and demonstrated no sign of thrombus formation. There was no significant difference at 1month between the treatment groups in lumen loss (0.64±0.43, 0.44±0.43 and 0.33±0.28mm for EES, DCB/EES and DCB/BMS respectively, p=0.37) and binary restenosis (6.86 (2.91–9.12), 4.93 (−1.53–10.7) and 4.18 (3.27–10.2)% respectively, p=0.87). OCT found mean neointimal thickness of 0.15±0.09, 0.07±0.03 and 0.08±0.03mm (p=0.05) for EES, DCB/EES and DCB/BMS respectively. Endothelial strut coverage was 92.3±5.5, 85.4±8.6 and 89.1±8.9% (p=0.05) and mean neointimal area was 1.06±0.42, 0.95±0.24 and 1.20±0.28mm2 (p=0.09) respectively. Inflammation score was similar between the three groups: 0.20 (0.20–0.28), 0.30 (0.22–0.48), 0.30 (0.20–0.38) for EES, DCB/EES and DCB/BMS respectively (p=0.14) and there were no differences in fibrin deposition. ConclusionsThe combination of DCB with EES appeared to be safe and effective. Using EES to bail out suboptimal DCB therapy appeared to be safe and effective in this porcine model.

Relationship between peri-strut low intensity areas and vascular healing response after everolimus-eluting bioresorbable scaffold implantation: An optical coherence tomography study

BackgroundPeri-strut low intensity areas (PLIA) surrounding metallic coronary stent struts on optical coherence tomography (OCT) images have been histologically related to delayed healing and inflammation, and have been associated with neointimal proliferation. The relationship between PLIA and vascular healing response after bioresorbable scaffold (BRS) implantation remains unclear. MethodsThis study includes 38 consecutive patients (50 scaffolds) evaluated using OCT 12 months after BRS implantation. Mean and percent neointimal area were quantified. A PLIA was defined as a peri-strut region with an homogenous lower intensity appearance than the surrounding tissue on OCT images without significant signal attenuation. Cross sections were scored as follows: score 0, no PLIA; score 1, <1 quadrant; score 2, ≥1 but <2 quadrants; score 3, ≥2 quadrants but <3 quadrants; and score 4, ≥3 quadrants. Scaffolds were divided into two groups (PLIA+ and PLIA−) based on the presence or absence of any PLIA in the scaffold segment. ResultsThe frequency of any PLIA within the scaffold segment was 70.0%. The median PLIA score per scaffold was 0.51 (interquartile range 0–1.07). Using both scaffold- and frame-level analysis, a significant positive correlation was observed between PLIA score and both mean and percent neointimal area. Mean and percent neointimal area were significantly higher in the PLIA+ group than in the PLIA− group (1.95±0.65mm2 vs. 1.51±0.27mm2, p<0.01 and 24.0±7.0% vs. 17.4±3.6%, p<0.01, respectively). ConclusionThe presence and extent of PLIA on OCT imaging after BRS implantation appears to be significantly associated with neointimal formation.

Neointimal coverage on acute vessel wall injuries after stenting: 6-month follow-up study.

Stent implantation often creates local vessel wall injuries which can be characterized in detail by optical coherence tomography (OCT). Little is known about the neointimal coverage at these areas. We aimed to evaluate neointimal coverage of vessel wall injuries area associated with stent implantation. We retrospectively selected patients implanted with sirolimus-eluting stents (SES) having excellent OCT images immediately after stent implantation and at the 6-month follow-up. All OCT cross-sectional images were divided into three groups: intra-stent tissue prolapse (ISTP) areas, intra-stent dissection flaps (ISDF) areas, and non-injuried areas. The neointimal coverage in included sections was evaluated at 6 months follow-up. Finally, 1690 cross-sectional images in 74 stents were analyzed totally. Among which, 240 images (14.20%) involved ISTP areas, 124 images (7.34%) at ISDF areas, and 1326 images (78.46%) at non-injuried areas. All ISTP and ISDF were disappeared at six months follow-up, Neointimal thickness at ISTP and ISDF areas increased significantly compared to the one in non-injuried areas (97.4±40.3μm vs. 68.4±47.6μm, P<0.001; 92.7±49.8μm vs. 68.4±47.6μm, P<0.001). Mean neointimal area of ISTP and ISDF areas was almost the same (0.8±0.3 mm2), which both had a significant difference compared to mean neointimal area (0.6±0.4mm2) at non-injuried areas (p1<0.001, p2=0.006). Intra-stent tissue prolapse and intra-stent dissection flaps have benign clinical course up to 6 months. The areas with these local complications, however, have greater neointimal hyperplasia compared to the non-injuried areas.

Chronic vascular response after self-expanding nitinol stent implantation in superficial femoral arteries: a serial intravascular ultrasound analysis

The mechanical properties of the self-expanding nitinol stents (SENS) and chronic biological stimulation on the wall from the SENS have not been fully investigated. This study evaluated the mechanical vascular response to SENS implantation in superficial femoral artery (SFA) lesions using serial volumetric intravascular ultrasound (IVUS). Twenty-five symptomatic patients due to de novo SFA lesions scheduled for SENS placement were prospectively enrolled. Serial IVUS studies were performed immediately after crossing with a guidewire, immediately after the procedure, and at a 8-month follow-up. Serial IVUS volumetric analysis was conducted after stent deployment and at follow-up. Mean stent, lumen and neointimal areas were calculated as the volume divided by the stent length, and the calcium arc was measured. At follow-up, SENS had increased 40.6% in overall volume. The chronic stent expansion tended to be larger, and the mean neointimal area at the 8-month follow-up was significantly larger in less calcified lesions compared to heavily calcified lesions. As a result, the mean late lumen area loss was significantly larger in lesions with calcium arcs of 0° and in the first and second quadrants than in those with calcium arcs in the third and fourth quadrants (2.8±7.2, 1.3±5.6, 0.6±5.9, 1.2±5.4, -0.8±5.2 mm(2), respectively; p<0.001). SENSs continued to enlarge with intimal proliferation over 8months in all lesions. Although arterial calcium affected the degree of chronic stent expansion during the follow-up period, neointimal proliferation was smaller in heavily calcified lesion compared to less calcified lesion following SENS implantation.

Safety and performance of the second-generation drug-eluting absorbable metal scaffold in patients with de-novo coronary artery lesions (BIOSOLVE-II): 6 month results of a prospective, multicentre, non-randomised, first-in-man trial

Absorbable scaffolds were designed to overcome the limitations of conventional, non-absorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds are commercially available. We aimed to assess the safety and performance of a novel second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with de-novo coronary artery lesions. We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or documented silent ischaemia, and a maximum of two de-novo lesions with a reference vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months 1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and a subgroup of patients was scheduled for intravascular ultrasound, optical coherence tomography, and vasomotion assessment. All patients were recommended to take dual antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01960504. Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37), and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients. Intravascular ultrasound assessments showed a preservation of the scaffold area (mean 6·24 mm(2) [SD 1·15] post-procedure vs 6·21 mm(2) [1·22] at 6 months) with a low mean neointimal area (0·08 mm(2) [0·09]), and optical coherence tomography did not detect any intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and two (2%) patients needed clinically driven target lesion revascularisation. No definite or probable scaffold thrombosis was observed. Our findings show that implantation of the DREAMS 2G device in de-novo coronary lesions is feasible, with favourable safety and performance outcomes at 6 months. This novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds for treatment of obstructive coronary disease. Biotronik AG.

Fatigue and in vivo validation of a peritoneum-lined self-expanding nitinol stent-graft.

To assess the fatigue and in vivo performance of a new stent-graft incorporating bovine peritoneum lining that is designed for application in peripheral vascular occlusive disease. Bovine peritoneum-lined stent-grafts were subjected to accelerated in vitro pulsatile fatigue and axial/torsional fatigue testing designed to simulate 10 years of physiological strain on the devices. At specified times the devices were evaluated for stent fracture, suture failure, or tissue tearing. Seven dogs underwent bilateral common iliac artery (CIA) balloon angioplasty injury with unilateral placement of the peritoneum-lined stent-graft. Angiography and intravascular ultrasound were performed prior to treatment, after treatment, and prior to sacrifice at 30 days. Vessels were perfusion fixed and histologically evaluated at 5 regions: above stent, proximal stent, mid stent, distal stent, and below stent. No evidence of stent, suture, or tissue failure was present during or after pulsatile and axial/torsional fatigue testing. At 30±0.3 days after implantation, all vessels were patent. The average lumen area at explantation across stented vessels was 25.45 mm(2). Lumen areas tended to be reduced above (23.57 mm(2)) and below (24.17 mm(2)) the stent. Lumen areas were consistent across stented regions at explantation (proximal stent 27.80 mm(2), mid stent 25.88 mm(2), and distal stent 25.81 mm(2)). The mean neointimal area in peritoneum-lined stents was 2.02±1.52 mm(2), with a neointima:media ratio of 1.03±0.50. These values were significantly lower in the above and below stent areas than in the stented regions, but there was no difference in either measure within the proximal, mid, or distal stent. The custom-designed peritoneum-lined stent-graft is promising for clinical peripheral applications due to its ability to resist relevant long-term physiological stresses and outstanding short-term patency rates in canine implantations.