In-vivo assessment of vascular injury for the prediction of in-stent restenosis.

BACKGROUND: Despite optimizations of coronary stenting technology, a residual risk of in-stent restenosis (ISR) remains. Vessel wall injury has important impact on the development of ISR. While injury can be assessed in histology, there is no injury score available to be used in clinical practice. METHODS: Seven rats underwent abdominal aorta stent implantation. At 4 weeks after implantation, animals were euthanized, and strut indentation, defined as the impression of the strut into the vessel wall, as well as neointimal growth were assessed. Established histological injury scores were assessed to confirm associations between indentation and vessel wall injury. In addition, stent strut indentation was assessed by optical coherence tomography (OCT) in an exemplary clinical case. RESULTS: Stent strut indentation was associated with vessel wall injury in histology. Furthermore, indentation was positively correlated with neointimal thickness, both in the per-strut analysis (r = 0.5579) and in the per-section analysis (r = 0.8620; both p ≤ 0.001). In a clinical case, indentation quantification in OCT was feasible, enabling assessment of injury in vivo. CONCLUSION: Assessing stent strut indentation enables periprocedural assessment of stent-induced damage in vivo and therefore allows for optimization of stent implantation. The assessment of stent strut indentation might become a valuable tool in clinical practice.

Effects of TCFA on stent neointimal coverage at 9 months after EXCEL drug-eluting stent implantation assessed by OCT.

BACKGROUND: The aim of this study was to investigate the effects of thin-cap fibroatheromas (TCFAs) on stent neointimal coverage at the 9­month follow-up after EXCEL stent implantation assessed by optical coherence tomography (OCT). METHODS: A total of 93 patients with non-ST elevation acute coronary syndrome (NSTEACS) who underwent EXCEL stent implantation were prospectively enrolled in the study and divided into a TCFA group (n = 47) and a non-TCFA group (n = 46) according to whether EXCEL stents covered the TCFAs. A TCFA was defined as a plaque with lipid content in more than one quadrant and fibrous cap thickness measuring less than 65 µm. The effect of TCFAs on stent neointimal coverage at the 9­month follow-up after stent implantation was evaluated by OCT. The primary study endpoints were the incidence of neointimal uncoverage and stent malapposition. RESULTS: At the 9­month follow-up, the minimal lumen diameter of the TCFA group tended to be smaller (2.8 ± 0.8 vs. 2.1 ± 0.8, p = 0.08) and the diameter of stenosis in the TCFA group tended to be larger (15.1 ± 10.3% vs. 26.3 ± 15.1%, p = 0.08) than those in the non-TCFA group. The mean intimal thickness of the TCFA group was significantly lower than that of the non-TCFA group (67.2 ± 35.5 vs. 145.1 ± 48.7, p < 0.001). The uncovered struts (10.1 ± 9.7 vs. 4.8 ± 4.3, p = 0.05) and malapposed struts (2.1 ± 4.7 vs. 0.3 ± 0.5, p = 0.003) in the TCFA group were more significant than those in the non-TCFA group. Multivariate analysis showed that TCFAs and lesion types were independent predictors of incomplete neointimal coverage (p < 0.05), and lesion types were independent predictors of stent malapposition (p < 0.05). CONCLUSION: In patients with NSTEACS, TCFAs delayed endothelium coverage at 9 months after stent implantation, and TCFAs were independent predictors of incomplete neointimal coverage of the stent.

Inflammatory Phenotype by OCT Coronary Imaging: Specific Features Among De Novo Lesions, In-Stent Neointima, and In-Stent Neo-Atherosclerosis. / Fenótipo Inflamatório por Imagem de OCT Coronária: Características Específicas Entre Lesões De Novo, Hiperplasia Intimal e Neoaterosclerose Intra-Stent.

BACKGROUND: Coronary stenosis can be caused de novo atherosclerosis, in-stent restenosis, and in-stent neoatherosclerosis, three entities that develop from a diverse pathophysiological milieu. OBJECTIVE: This study aims to investigate, using optical coherence tomography (OCT), whether or not coronary lesions related to these processes differ in their local inflammatory profile. METHODS: Retrospective analysis of patients with diagnosed or suspected coronary lesions who had undergone OCT imaging for clinical reasons. Macrophage and intra-plaque neovascularization were assessed by OCT and used as surrogates of local inflammation. A significance level of < 0.05 was adopted as statistically significant. RESULTS: From the 121 lesions, 74 were de novo, 29 were restenosis, and 18 were neoatherosclerosis. Neovascularization was found in 65.8% of de novo, 10.3% in restenosis, and 94.4% in neoatherosclerosis (p<0.01 for all). The volume of neovascularization was different among lesion types (950 vs. 0 vs. 6220, respectively [median values in 1000 x µm3/mm]; p<0.01 for all), which were significantly higher in neoatherosclerosis and lower in restenosis. The presence of macrophages differed among the lesions (95.9% in de novo vs. 6.9% in restenosis vs. 100% in neoatherosclerosis [p<0.01 for all]). Moreover, the intensity of macrophagic infiltration was different among lesion types (2.5 vs. 0.0 vs. 4.5, respectively [median values of macrophage score]; p<0.01 for all), significantly higher in neoatheroscleosis and lower in restenosis. CONCLUSION: When compared using coronary OCT, de novo atherosclerosis, in-stent restenosis, and neoatherosclerosis presented markedly different inflammatory phenotypes.

FUNDAMENTO: A estenose coronária pode ser causada por de novo aterosclerose, reestenose intra-stent e neoaterosclerose intra-stent, três entidades que se desenvolvem a partir de diversos meios fisiopatológicos. OBJETIVOS: Este estudo tem como objetivo investigar, por meio da tomografia de coerência óptica (OCT), se as lesões coronarianas relacionadas a esses processos diferem em seu perfil inflamatório local. MÉTODOS: Análise retrospectiva de pacientes com lesões coronárias diagnosticadas ou suspeitas que realizaram exames de OCT por motivos clínicos. Macrófagos e neovascularização intraplaca foram avaliados por OCT e utilizados como marcadores de inflamação local. O nível de significância < 0,05 foi adotado como estatisticamente significante. RESULTADOS: Das 121 lesões, 74 eram de novo , 29 eram reestenose e 18 eram neoaterosclerose. Neovascularização foi encontrada em 65,8% das de novo , 10,3% na reestenose e 94,4% na neoaterosclerose (p<0,01 para todos). O volume de neovascularização foi diferente entre os tipos de lesão (950 vs. 0 vs. 6.220, respectivamente [valores medianos em 1000 x µm 3 /mm]; p<0,01 para todos), sendo significativamente maior na neoaterosclerose e menor na reestenose. A presença de macrófagos diferiu entre as lesões (95,9% em de novo vs. 6,9% em reestenose vs. 100% em neoaterosclerose [p<0,01 para todos]). Além disso, a intensidade da infiltração macrofágica foi diferente entre os tipos de lesão (2,5 vs. 0,0 vs. 4,5, respectivamente [valores medianos do escore de macrófagos]; p<0,01 para todos), significativamente maior na neoaterosclerose e menor na reestenose. CONCLUSÕES: Quando comparados pela OCT coronariana, de novo , reestenose intra-stent e neoaterosclerose apresentaram fenótipos inflamatórios marcadamente diferentes.

Relationship between neointimal strut bridge and jailed side-branch ostial area.

BACKGROUND: Our study analyzed the relationship between the neointimal strut bridge and jailed side-branch (SB) ostial area in patients with coronary heart disease (CHD) who had a single drug-eluting stent (DES) crossover of the left anterior descending coronary artery (LAD)/diagonal branch (D) bifurcation. PATIENTS AND METHODS: A total of 64 CHD patients with an LAD/D bifurcation treated by optical coherence tomography (OCT)-guided single-DES implantation and followed up at 1 year after primary percutaneous intervention (pPCI) were enrolled in our study. According to the two-dimensional OCT results, patients were divided into a non-neointimal bridge group (n = 44) and a neointimal bridge group (n = 20). Basic clinical, angiographic, 2D and 3D OCT, and DES results were analyzed. RESULTS: The blood lipid levels of the two groups after the 1­year follow-up were lower than the levels 1 year earlier (p < 0.05). There was a notable decrease in the SB ostial minimum lumen diameter and area directly after pPCI vs. before pPCI in both groups. The diameter stenosis directly after pPCI showed a clear increase compared with the pre-pPCI value in both groups (p < 0.05 or p < 0.01, respectively). The strut distance of the neointimal bridges in the neointimal bridge group was greater than in the non-neointimal bridge group (p < 0.05). A clearly short strut distance of the neointimal bridge was observed compared with the strut distance of the non-neointimal bridge in the neointimal bridge group (p < 0.05). A larger neointimal bridge area and a smaller SB ostial area were found in the neointimal bridge group compared with the non-neointimal bridge group (p < 0.05 or p < 0.01, respectively). CONCLUSION: A short strut distance facilitated formation of a neointimal bridge, which significantly influenced the SB ostial area after single crossover stenting of the SB orifice at the 1­year follow-up.

Clinical outcomes by optical characteristics of neointima and treatment modality in patients with coronary in-stent restenosis.

BACKGROUND: Drug-coated balloons (DCB) and drug-eluting stents (DES) represent the currently recommended treatments for in-stent restenosis (ISR). Optical coherence tomography (OCT) allows detailed neointimal characterisation which can guide treatment strategies. AIMS: The aims of this study were first, to assess the relation between neointimal pattern and clinical outcomes following in-stent restenosis (ISR) treatment, and second, to explore a potential interaction between neointimal pattern and treatment modality relative to clinical outcomes. METHODS: Patients undergoing OCT-guided treatment (DCB or DES) of ISR in three European centres were included. Based on the median of distribution of non-homogeneous neointima quadrants, patients were categorised into low and high inhomogeneity groups. RESULTS: A total of 197 patients (low inhomogeneity=100 and high inhomogeneity=97) were included. There were no significant differences in terms of major adverse cardiac events (MACE) (p=0.939) or target lesion revascularisation (TLR) (p=0.732) between the two groups. The exploratory analysis showed a significant interaction between neointimal pattern and treatment modality regarding MACE (pint=0.006) and TLR (pint=0.022). DES showed a significant advantage over DCB in the high (MACE: HR 0.26 [0.10-0.65], p=0.004; TLR: HR 0.28 [0.11-0.69], p=0.006), but not in the low inhomogeneity group (MACE: p=0.917; TLR: p=0.797). CONCLUSIONS: In patients with ISR treated with DCB or DES, there were no significant differences in terms of MACE or TLR between the low and high inhomogeneity groups. A significant interaction was observed between treatment modality and neointimal pattern with an advantage of DES over DCB in the high and no difference in the low inhomogeneity group. This warrants confirmation from prospective dedicated studies.

Impact of Neointimal Condition and Platelet Reactivity on Intrastent Thrombus at Long-Term Follow-up After 2nd- and 3rd-Generation Drug-Eluting Stent Implantation　- Insights From a Coronary Angioscopy and Pharmacodynamic Study.

BACKGROUND: Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. CONCLUSIONS: Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

In Vivo Evaluation of Tissue Protrusion by Using Optical Coherence Tomography and Coronary Angioscopy Immediately After Stent Implantation.

BACKGROUND: The relationship between the characteristics of tissue protrusion detected by using optical coherence tomography (OCT) and the findings of coronary angioscopy (CAS) immediately after stent implantation were evaluated.Methods and Results:A total of 186 patients (192 stents) underwent OCT before and after stenting and were observed by using CAS immediately after stenting and at the chronic phase. Patients were assigned to irregular protrusion, smooth protrusion, and disrupted fibrous tissue protrusion groups according to OCT findings. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after stent implantation. The grade of yellow color (YC) and neointimal coverage (NC), and incidence of thrombus in the stented segment were evaluated by using CAS. After stent implantation, maximum YC grade (smooth, 0.64±0.80; disrupted fibrous tissue, 0.50±0.77; irregular, 1.50±1.09; P<0.0001), a prevalence of Max-YC grade of 2 or 3 (smooth, 17%; disrupted fibrous tissue, 17%; irregular, 50%; P<0.0001) and thrombus (smooth, 15%; disrupted fibrous tissue, 10%; irregular, 69%; P=0.0005), and elevated hs-CRP levels (smooth, 0.22±0.89; disrupted fibrous tissue, -0.05±0.29; irregular, 0.75±1.41; P=0.023) were significantly higher in irregular protrusion than in the other 2 groups. In the chronic phase, maximum- and minimum-NC grade and heterogeneity index, and thrombus did not differ significantly among the 3 groups. CONCLUSIONS: Irregular protrusion was associated with atherosclerotic yellow plaque, incidence of thrombus, and vascular inflammation. The angioscopic findings in the chronic phase may endorse the clinical efficacy of second- and third-drug eluting stents, regardless of the tissue protrusion type.

Angioscopic Assessments at 3 Months After Fluoropolymer-Based Paclitaxel-Eluting Stent Implantation for Femoropopliteal Endovascular Intervention.

BACKGROUND: The detailed mechanism of early-phase arterial healing after novel fluoropolymer-based paclitaxel-eluting stent (PES) implantation in the femoropopliteal (FP) lesions has not been elucidated.Methods and Results:We evaluated the intravascular status of 20 PES implanted in 11 FP lesions of 9 patients using angioscopy at approximately 3 months after implantation. Angioscopic images were analyzed to determine (1) the dominant degree of neointimal coverage (NIC) over the stent; (2) the extent of uncovered struts; and (3) the presence of intrastent thrombus. NIC was classified into 4 grades: grade 0, stent struts fully visible; grade 1, stent struts bulging into the lumen although covered; grade 2, stent struts embedded in neointima, but translucently visible; grade 3, stent struts fully embedded and invisible. The extent of uncovered struts was scored as follows: score 0, no uncovered struts of the entire stent; score 1, uncovered struts area approximately <30% of the stent; and score 2, uncovered struts area approximately ≥30% of the stent. In total, 90% of stents demonstrated grade 1 dominant NIC and 10% showed grade 2 dominant NIC; 85% of stents showed an uncovered stent score of 0, and the remainder had a score of 1. Thrombus was observed in all stents. CONCLUSIONS: Widely uncovered stent struts were not observed by angioscopy at 3 months after PES implantation in these FP lesions, even with the detection of thrombus adhesion.

Neointima characteristics as a prognostic marker for drug-coated balloon angioplasty in patients with in-stent restenosis: an optical coherence tomography study.

BACKGROUND: Research has shown that the prognosis of in-stent restenosis (ISR) lesions after drug-coated balloon (DCB) angioplasty can differ in relation to in-stent neointimal characteristics. However, changes in neointima characteristics after DCB have not been studied. This study sought to investigate changes in neointima characteristics after DCB for ISR. METHODS: From the Yonsei Optical Coherence Tomography (OCT) registry, data on DCBs performed in patients with ISR were collected. Neointima characteristics were categorized as homogeneous, heterogeneous, layered neointima, and neoatherosclerosis in each OCT procedure. Homogeneous and layered neointima were classified as a favorable neointima, while heterogeneous neointima and neoatherosclerosis were classified as an unfavorable neointima. The data of 67 ISR patients were analyzed. RESULTS: The median duration between initial and follow-up OCT was 9.6 months. Patients with homogeneous and layered neointima on the initial OCT before DCB mostly appeared as homogeneous (66.7 and 68.2%, respectively) on the follow-up OCT, whereas most of the patients with heterogeneous neointima on the initial OCT remained unaltered (70%). Patients with unfavorable neointima at either the initial (P = 0.023) or the follow-up OCT (P = 0.037) had a worse major adverse cardiovascular event-free survival than the other patients. Patients who showed unfavorable neointima at both the initial and the follow-up OCT had the worst event-free survival (P = 0.038). CONCLUSIONS: The follow-up OCT neointimal characteristics after DCB for ISR was associated with initial OCT characteristics. Sustained unfavorable neointima in serial OCT imaging may reflect poor prognosis in patients with ISR treated with DCB.

Incidence and Predictors of Neoatherosclerosis in Patients with Early In-Stent Restenosis Determined Using Optical Coherence Tomography.

In-stent restenosis (ISR) still exists after drug-eluting stent (DES) implantation, even up to one year. The incidence and risk factors for neoatherosclerosis in patients with early ISR have not yet been elucidated. Here, we used optical coherence tomography (OCT) to evaluate the incidence and predictors of neoatherosclerosis in patients with early ISRs.OCT was performed on ISR lesions in 185 patients in order to detect neoatherosclerosis. The median follow-up was 180 days, and neoatherosclerosis was detected in 37% of early ISR lesions. According to the presence of neoatherosclerosis, patients with ISR were divided into two groups: neoatherosclerosis (group A, n = 69) and non-neoatherosclerosis (group B, n = 116) groups.The risk factors were similar, except for hypercholesterolemia. Moreover, the tissue characteristics were not significantly different between patients with and without neoatherosclerosis. Follow-up low-density lipoprotein-cholesterol (LDL-C) levels were divided into three grades (LDL < 70 mg/dL, 70 mg/dL≤ LDL < 100 mg/dL, and LDL ≥ 100 mg/dL). The incidence of neoatherosclerosis was significantly lower (23% versus 57%, P < 0.0001) in the LDL < 70 mg/dL group. There was no significant difference in the incidence of neoatherosclerosis in patients with lipid levels between 70 and 100 mg/dL (P = 0.53). However, neoatherosclerosis was significantly more common in patients with a follow-up LDL-C level > 100 mg/dL (45% versus 15%, P < 0.0001).In patients with early ISR lesions, the LDL-C levels may be related to the formation and progression of early neoatherosclerosis, and poor LDL-C control may be a risk factor for the occurrence of early-stage neoatherosclerosis following DES implantation.

18-Year Follow-Up After Coronary Stenting for Left Main Coronary Artery Lesions.

The current treatment of radiation-induced coronary artery disease (RCAD) is comparable to that of generic coronary artery disease (CAD); however, the outcomes of these treatment measures have not been fully examined in RCAD. A 33-year-old woman, without conventional cardiovascular risk factors, presented with left main coronary artery (LMCA) lesions. At the age of 26, she received mediastinal radiation therapy (RT) to treat mixed cellularity Hodgkin lymphoma. One BiodivYsio 3.5 × 18 mm stent was implanted at the LMCA site. At the age of 38, the patient was treated by balloon dilatation because of approximately 50% in-stent stenosis. At the last follow-up in February 2018, when the patient was 51 years old, she no longer complained of chest pain. Coronary angiography showed no de novo or in-stenosis lesions, although optical coherence tomography showed mild neointimal proliferation, calcific plaque, small ruptured intima, and several uncovered struts. The experience of treating this case may shed some light on coronary stenting in coronary lesions caused by RCAD.

Concomitant Use of Rosuvastatin and Eicosapentaenoic Acid Significantly Prevents Native Coronary Atherosclerotic Progression in Patients With In-Stent Neoatherosclerosis.

BACKGROUND: In-stent neoatherosclerosis (NA) is a risk for future cardiovascular events through atherosclerotic progression in non-stented lesions. Using optical coherence tomography, this study assessed the efficacy of intensive therapy with 10 mg/day rosuvastatin plus 1,800 mg/day eicosapentaenoic acid (EPA) vs. standard 2.5 mg/day rosuvastatin therapy on native coronary plaques in patients with NA.Methods and Results:This was a subgroup analysis of the randomized LINK-IT trial, which was designed to compare changes in the lipid index in NA between intensive and standard therapy for 12 months. In all, 42 patients with native coronary plaques and NA were assessed. Compared with standard therapy, intensive therapy resulted in greater decreases in serum low-density lipoprotein cholesterol concentrations and greater increases in serum 18-hydroxyeicosapentaenoic acid concentrations, with significantly greater decreases in the lipid index and macrophage grade in both NA (-24 vs. 217 [P<0.001] and -15 vs. 24 [P<0.001], respectively) and native coronary plaques (-112 vs. 29 [P<0.001] and -17 vs. 1 [P<0.001], respectively) following intensive therapy. Although there was a greater increase in the macrophage grade in NA than in native coronary plaques in the standard therapy group, in the intensive therapy group there were comparable reductions in macrophage grade between NA and native coronary plaques. CONCLUSIONS: Compared with standard therapy, intensive therapy prevented atherosclerotic progression more effectively in native coronary plaques in patients with NA.

Influence of Self-Expanding Paclitaxel-Eluting Stent Sizing on Neointimal Hyperplasia in Superficial Femoral Artery Lesions.

BACKGROUND: Although self-expanding drug-eluting stents (DES) have recently shown superior outcomes for superficial femoral artery (SFA) lesions, optimal sizing of DES diameter in SFA intervention is unclear.Methods and Results:A total of 40 de novo SFA lesions were randomized 1:1 to receive self-expanding DES with either a 1-mm or 2-mm larger diameter than the reference vessel diameter. Follow-up optical coherence tomography (OCT) was scheduled 6 months after DES implantation to evaluate the vascular response to the stents. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was neointimal VI at 6 months. Baseline reference vessel diameter was similar between the 1-mm larger diameter group and the 2-mm larger diameter group (5.0±0.8 mm vs. 4.7±0.9 mm, P=0.35). Stent diameter was 6.3±0.6 mm in the 1-mm larger group and 7.1±0.6 mm in the 2-mm larger group (P<0.0001), and stent to reference vessel diameter ratio (SV ratio) was 1.3±0.2 and 1.5±0.2 (P<0.0001), respectively. At 6-month, neointimal VI was greater in the 2-mm larger diameter group (5.5±1.5 mm2vs. 9.6±3.4 mm2, P<0.001). The correlation analysis revealed that degree of neointimal VI was positively correlated with SV ratio (r=0.43, P<0.01). CONCLUSIONS: Implantation of self-expanding DES with a considerably high SV ratio resulted in neointimal hyperplasia in SFA lesions.

Comparison of post-stent irregular protrusion and subsequent neointimal characteristics between second- and third-generation drug-eluting stent implantation.

BACKGROUND: Third-generation drug-eluting-stents (3rd DES) may improve coronary arterial healing and reduce neoatherosclerosis formation. We evaluated post-stent findings and subsequent vascular healing of 3rd DES by comparing to second-generation drug-eluting-stents (2nd DES) at intermediate-term follow-up using optical coherence tomography (OCT). METHOD: We evaluated 170 patients with 170 lesions who underwent DES implantation (2nd DES, n = 98; 3rd DES, n = 72) and OCT-guided follow-up examination. After propensity score (PS) matching for baseline clinical characteristics, OCT findings from 56 pairs of patients with 2nd DES and 3rd DES implants were compared. Post-stent irregular protrusion (IP) was defined as the protrusion of material with an irregular surface into the lumen between the stent struts. Neoatheroscleosis was defined as neointima contained heterogeneous pattern, rupture, lipid-laden, thin-cap fibroatheroma, or calcification. The presence of peri-strut low-intensity area (PLIA) and in-stent neointimal tissue characteristics were also analyzed at 6- to 8-month follow-up. RESULTS: There were no significant differences between the incidence of post-stent IP or neoatherosclerosis formation in the 2nd DES and the 3rd DES (45% vs. 38%, p = 0.44; 30% vs. 20%, p = 0.19, respectively). However, the incidences of PLIA and layered neointimal pattern, which indicate immature neointimal healing, were significantly lower in the 3rd DES compared to the 2nd DES (41% vs. 61%, p = 0.04; 2% vs. 11%, p = 0.04, respectively). As comparing intermediate-term follow-up OCT neointimal findings in patients with IP between 2nd DES and 3rd DES, most neointima tended to have a homogeneous pattern (95% versus 76%, p = 0.06) in the 3rd DES than in the 2nd DES. CONCLUSIONS: The incidence of post-stent IP and subsequent neoatherosclerosis formation at intermediate-term follow-up after stent implantation were similar between patients with 2nd DES and 3rd DES, however, vascular healing might be favorable when using 3rd DES.

Peri-strut low intensity areas and in-scaffold neointima growth after bioresorbable scaffold implantation in STEMI. A serial optical coherence tomography study.

BACKGROUND: Peri-strut low intensity areas (PLIA) visualized by optical coherence tomography (OCT) have been related to neointimal proliferation and increased incidence of target lesion revascularization in stable coronary artery disease. The aim of this study was to determine the association between PLIA by OCT and the long-term vascular healing response after bioresorbable scaffold (BRS) implantation in the setting of ST-segment elevation myocardial infarction (STEMI). METHODS: This is a single-centre, longitudinal, cohort study with a serial: baseline, 1, 2 and 5 years OCT evaluation of neointimal response (lumen area and neoatherosclerosis) after percutaneous coronary intervention (PCI) with BRS Absorb™ 1.0 implantation in patients presenting with STEMI. PLIA was analyzed in every cross section and scored: 0-no PLIA; 1-PLIA < 1 quadrant; 2-PLIA ≥ 1 and <2 quadrants; 3-PLIA ≥ 2 and <3 quadrants; 4-PLIA in ≥3 quadrants. RESULTS: Of the 23 patients implanted BRS, 18 completed 2-year follow-up, whereas complete OCT data up to 5 years were available in 12 patients. Presence of PLIA was identified in 100% patients at 1 and 2 years, whereas at 5 years neither PLIA nor scaffold struts were visualized by OCT. Neoatherosclerosis was identified in 73,68% patients after 1 year and in all patients at 2 and 5 years. The mean PLIA score > 1 at 2 years was associated with greater percentage of minimum lumen area decrease after 2 years from index procedure. CONCLUSIONS: The extent of PLIA by OCT at 2 years after primary PCI with BRS was associated with lumen area decrease. Neoatherosclerosis formation was detected in all patients at 2 and 5 years. PLIA assessment could serve as an additive means to predict neointimal healing pattern after next generation BRS implantation.

Echolucent carotid plaque is associated with restenosis after carotid endarterectomy.

OBJECTIVE: The mechanism of carotid endarterectomy (CEA) restenosis remains unclear. Our research aimed to investigate the relationship between the carotid plaque grayscale median (GSM) value and restenosis after CEA. METHODS: Between January 2010 and January 2018, 1280 consecutive patients underwent CEA at our institution; 32 patients were diagnosed with restenosis by ultrasound at 1 year after CEA. The correlations between plaque GSM, plaque echogenicity, clinical manifestations, shunting, and restenosis were analyzed. RESULTS: In total, 829 patients were ultimately enrolled; 32 (4%) presented diagnoses of restenosis (mean age 67.3 ± 8.0 years, 81.2% men). The GSM value was lower in the restenosis group (68.1 ± 19.9 vs 59.9 ± 14.7, p = 0.02). After multiple logistic regression analysis, the GSM value was found to be an independent risk factor for restenosis (OR 0.976, 95% CI 0.957-0.995). Shunting was another significant independent risk factor for restenosis (OR 2.39, 95% CI 1.07-5.34). The GSM cutoff value for predicting restenosis was 75 (sensitivity 0.38, specificity 0.84, area under the curve 0.62). We separated the patients into 2 groups by GSM (GSM ≤ 75 and GSM > 75 subgroups). Comparison of the 2 groups indicated that symptomatic manifestation was related to restenosis in the subgroup with GSM ≤ 75, indicating predominantly echolucent plaques, but not in the subgroup with GSM > 75, indicating predominantly echogenic plaques. CONCLUSIONS: Predominantly echolucent carotid plaques, as measured by GSM, had a higher restenosis risk at 1 year than echogenic plaques.

Endovascular procedures cause transient endothelial injury but do not disrupt mature neointima in Drug Eluting Stents.

Extensive application of coronary intravascular procedures has led to the increased need of understanding the injury inflicted to the coronary arterial wall. We aimed to investigate acute and prolonged coronary endothelial injury as a result of guidewire use, repeated intravascular imaging and stenting. These interventions were performed in swine (N = 37) and injury was assessed per coronary segment (n = 81) using an Evans Blue dye-exclusion-test. Scanning electron microscopy and light microscopy were then used to visualize the extent and nature of acute (<4 hours) and prolonged (5 days) endothelial injury. Guidewire and imaging injury was mainly associated with denudation and returned to control levels at 5 days. IVUS and OCT combined (Evans Blue staining 28 ± 16%) did not lead to more acute injury than IVUS alone (33 ± 15%). Stent placement caused most injury (85 ± 4%) and despite early stent re-endothelialization at 5 days, the endothelium proved highly permeable (97 ± 4% at 5 days; p < 0.001 vs acute). Imaging of in-stent neointima at 28 days after stent placement did not lead to neointimal rupture. Guidewire, IVUS and OCT induce acute endothelial cell damage, which does not increase during repeated imaging, and heals within 5 days. Interestingly, endothelial permeability increases 5 days post stenting despite near complete re-endothelialization.

Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation.

RATIONALE: Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms. OBJECTIVE: We used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models. METHODS AND RESULTS: Adipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated. CONCLUSIONS: We present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume. Visual Overview: An online visual overview is available for this article.

Treatment of In-Stent Restenosis by Excimer Laser Coronary Atherectomy and Drug-Coated Balloon: Serial Assessment with Optical Coherence Tomography.

OBJECTIVES: We aimed to compare the results of neointimal modification before drug-coated balloon (DCB) treatment with excimer laser coronary atherectomy (ELCA) plus scoring balloon predilation versus scoring balloon alone in patients presenting with in-stent restenosis (ISR). BACKGROUND: Treatment of ISR with ELCA typically results in superior acute gain by neointima debulking. However, the efficacy of combination therapy of ELCA and DCB remains unknown. METHODS: A total of 42 patients (44 ISR lesions) undergoing DCB treatment with ELCA plus scoring balloon (ELCA group, n = 18) or scoring balloon alone (non-ELCA group, n = 24) were evaluated via serial assessment by optical coherence tomography (OCT) performed before, after intervention, and at 6 months. RESULTS: Although there was significantly greater frequency of diffuse restenosis and percent diameter stenosis (%DS) after intervention in the ELCA group, comparable result was shown in %DS, late lumen loss, and binary angiographic restenosis at follow-up. On OCT analysis, a decreased tendency in the minimum lumen area and a significant decrease in the minimum stent area were observed in the ELCA group between 6-month follow-up and after intervention (-0.89 ± 1.36 mm2 vs. -0.09 ± 1.25 mm2, p = 0.05, -0.49 ± 1.48 mm2 vs. 0.28 ± 0.78 mm2, p = 0.03, respectively). The changes in the neointimal area were similar between the groups, and target lesion revascularization showed comparable rates at 1 year (11.1% vs. 11.4%, p = 0.85). CONCLUSIONS: Despite greater %DS after intervention, ELCA before DCB had possible benefit for late angiographic and clinical outcome.