Angioscopic Evaluation of Atrial Septal Defect Closure Device Neo‐Endothelialization

Background Current guidelines recommend at least 6 months of antithrombotic therapy and antibiotic prophylaxis after septal‐occluding device deployment in transcatheter closure of atrial septal defect. It has been estimated that it takes ≈6 months for complete neo‐endothelialization; however, neo‐endothelialization has not previously been assessed in vivo in humans. Methods and Results The neointimal coverage of septal occluder devices was evaluated 6 months after implantation in 15 patients by angioscopy from the right atrium. Each occluder surface was divided into 9 areas; the levels of endothelialization in each area were semiquantitatively assessed by 4‐point grades. Device neo‐endothelialization was sufficient in two thirds of patients, but insufficient in one third. In the comparison between patients with sufficiently endothelialized devices of average grade score ≥2 (good endothelialization group, n=10) and those with poorly endothelialized devices of average grade score <2 (poor endothelialization group, n=5), those in the poor endothelialization group had larger devices deployed (27.0 mm [25.0–31.5 mm] versus 17.0 mm [15.6–22.5 mm], respectively) and progressive right heart dilatation. The endothelialization was poorer around the central areas. Moreover, the prevalence of thrombus formation on the devices was higher in the poorly endothelialized areas than in the sufficiently endothelialized areas (Grade 0, 94.1%; Grade 1, 63.2%; Grade 2, 0%; Grade 3, 1.6%). Conclusions Neo‐endothelialization on the closure devices varied 6 months after implantation. Notably, poor endothelialization and thrombus attachment were observed around the central areas and on the larger devices.

Mobilization of progenitor cells and vessel healing after implantation of SYNERGY in acute coronary syndrome

This study was aimed to compare the vascular healing process of a SYNERGY stent with that of a PROMUS PREMIER stent in patients with acute coronary syndrome (ACS). In 71 patients with ACS, undergoing coronary stent implantation using the SYNERGY stent (n = 52) or PROMUS PREMIER stent (n = 19), we measured circulating CD34+/CD133+/CD45null cells and CD34+/KDR+ cells and observed vascular healing at the stented sites using optical coherence tomography (OCT) and coronary angioscopy. On the day 7, circulating CD34+/CD133+/CD45null cells increased in SYNERGY group (P < 0.0001), while it did not change in PROMUS group. The CD34+/KDR+ cells also increased in SYNERGY group (P < 0.0001) but less significantly in the PROMUS group (P < 0.05). The OCT-based neointimal thickness (P < 0.0005) and neointimal coverage rate (P < 0.05) at 12 months were greater in SYNERGY group, compared with PROMUS group. The coronary angioscopy-based neointimal coverage grade at 12 months was also greater in SYNERGY group (P < 0.001). In overall patients, the change in CD34+/KDR+ cells on the day 7 correlated with the OCT-based neointimal thickness at 12 months (R = 0.288, P < 0.05). SYNERGY stent seems to have potential advantages over PROMUS PREMIER stent for ACS patients in terms of vascular healing process at the stented sites.

Successful sealing of a coronary aneurysm by novel, second-generation, covered stent implantation: First report of optical coherence tomography and coronary angioscopy evaluation

After successful sealing of a coronary aneurysm by PK Papyrus covered stent implantation, the intravascular assessment by OCT and angioscopy showed single-layered neointimal coverage without recurrence of the aneurysm.

Mobilization of Progenitor Cells and Vessel Healing After Implantation of Synergytm in Acute Coronary Syndrome

This study was aimed to compare the vascular healing process of a SYNERGYTM stent with that of a PROMUS PREMIERTM stent in patients with acute coronary syndrome (ACS). In 71 patients with ACS, undergoing coronary stent implantation using the SYNERGYTM stent (n=52) or PROMUS PREMIERTM stent (n=19), we measured circulating CD34+/CD133+/CD45null cells and CD34+/KDR+ cells and observed vascular healing at the stented sites using optical coherence tomography (OCT) and coronary angioscopy. On the day 7, circulating CD34+/CD133+/CD45null cells increased in SYNERGY group (P<0.0001), while it did not change in PROMUS group. The CD34+/KDR+ cells also increased in SYNERGY group (P<0.0001) but less significantly in the PROMUS group (P<0.05). The OCT-based neointimal thickness (P<0.0005) and neointimal coverage rate (P<0.05) at 12 months were greater in SYNERGY group, compared with PROMUS group. The coronary angioscopy-based neointimal coverage grade at 12 months was also greater in SYNERGY group (P<0.001). In overall patients, the change in CD34+/KDR+ cells on the day 7 correlated with the OCT-based neointimal thickness at 12 months (R=0.288, P<0.05). SYNERGYTM stent seems to have potential advantages over PROMUS PREMIERTM stent for ACS patients in terms of vascular healing process at the stented sites.

Similar degree of intimal coverage and apposition among drug-eluting stents with persistent, absorbable or without polymer at 1 and 6 months after implantation

Background Despite technological advances in drug-eluting stents (DES) design, delayed vascular healing is still a problem, triggered by the polymers among others. This may induce restenosis and thrombosis. The development of biodegradable polymers and DES without polymer is thought to improve the vascular response and enhance earlier neointimal healing. Optical coherence tomography (OCT) is the best intracoronary imaging tool to evaluate endothelial coverage after stent implantation. Purpose We aimed to quantitatively assess the differences on intimal coverage between biodegradable-polymer, durable-polymer and without-polymer DES at 1 and 6-month follow-up OCT. Methods A total of 94 patients with de novo coronary lesions were treated with DES: 26% were treated with Biolimus A9 (BA9) stent without polymer, 30% were treated with Everolimus DES with biodegradable polymer (EESb) and 44% with Everolimus DES with persistent polymer (EESp). OCT analysis was performed blindly at an independent Core Lab at three stages: implantation, after one month and after six months. The primary endpoint was to compare neointimal coverage and apposition of these three different types of DES with OCT at one and six months after implantation. Results A total of 16034 struts were analysed (24% BA9, 29% EESb and 47% EESp). No significant differences were found among the groups regarding baseline clinical characteristics. When studying the strut coverage, it is remarkable the relatively low percentage of early neointimal coverage with no significant differences among stents one month after implantation (84–87%). After six months, there was better coverage in the three stent groups compared with one month (p&lt;0.001). The stents without polymer had better neointimal coverage at six months compared with the stents with persistent polymer (99% vs 92%, p=0.0002). No significant differences were found in the strut apposition after one or six months among the three stent types. However, the rate of apposition was higher after six months compared with one month in all stent groups (p=0,001). No significant differences were found in the neointimal hyperplasia at one month among the three stent groups. At six months there was a higher hyperplasia in the stent without polymer compared to the stent with persistent polymer (164μm vs 92μm, p=0,003). The degree of hyperplasia after six months was higher compared to one month in all groups (p=0,001). Conclusions The new-generation DES with biodegradable-polymer or without polymer showed relatively poor early neointimal coverage and similar to the last generation durable-polymer EES. According to these results, DAPT may not be shortened in any of the three DES types studied. Funding Acknowledgement Type of funding source: None

Angioscopic evaluation of vascular healing at 1 and 12 months after drug-coated stent implantation

Background Polymer- and carrier-free Biolimus-A9-coated stent (DCS) is expected better vascular healing compared with conventional durable polymer drug-eluting stents (DES). Moreover, DCS had been demonstrated in clinical trials to allow one-month short dual antiplatelet therapy, which might achieve sufficient healing at only 1 month after implantation. However, the process of vascular healing after DCS implantation has not been elucidated by angioscopic observation. Purpose To evaluate the process of vascular healing at 1 month and 12 months after DCS implantation. Methods This study included 57 patients treated with DCS or durable polymer everolimus-eluting stents (EES) in our hospital from April 2017 to April 2019. Firstly, the angioscopic findings of DCS at 1 month (n=16) and 12 months (n=14) after implantation were respectively compared with EES at 12 months after implantation (EES-12, n=35) as a standard healing status of DES. Secondary, angioscopic findings of DCS at 1 month and 12 months after implantation were compared among the serially observed eight patients. Neointimal coverage (NIC) grade, yellow colour grade, and the presence of thrombus were evaluated. NIC grade was classified as grade 0 (no neointimal coverage), grade 1 (struts were bulged into lumen but covered), grade 2 (struts were embedded in the neointima but visible), or grade 3 (struts were fully embedded and invisible). Yellow colour grade was classified as grade 0 (white), grade 1 (light yellow), grade 2 (yellow), or grade 3 (intensive yellow). Results At 1 month after DCS implantation, dominant NIC grade was lower (0.3±0.5 vs. 1.5±0.7, p&lt;0.001) and the frequency of thrombus was higher (38% vs. 6%, p=0.008) than EES-12. On the other hands, at 12 months after DCS implantation, dominant NIC grade was higher (2.1±0.6 vs. 1.5±0.7, p=0.013) and the frequency of thrombus was not different (7% vs. 6%, p=1.000) in comparison with EES-12. By serial observation of DCS, dominant NIC grade was higher at 12 months than at 1 month (2.3±0.5 vs. 0.4±0.5, p&lt;0.001), while yellow colour grade (1.0±0.5 vs. 1.5±1.2, p=0.227) and the frequency of thrombus adhesion (0% vs. 38%, p=0.200) were not different. Conclusion Compared with EES-12, vascular healing of DCS was inferior at 1 month but superior at 12 months. Figure 1 Funding Acknowledgement Type of funding source: None

Comparison of neointimal coverage between biodegradable-polymer everolimus-eluting stent and durable-polymer everolimus-eluting stent using angioscopy for the patients with acute coronary syndrome

Background New-generation biodegradable-polymer platinum chromium everolimus-eluting stent (BP-PtCr-EES) is available, which has different polymer and alloy compare to more established stent design, a durable-polymer cobalt-chromium everolimus-eluting stent (DP-CoCr-EES). Purpose To compare neointimal coverage (NIC) between BP-PtCr-EES and DP-CoCr-EES by using coronary angioscopy (CAS). Methods A total of 36 patients (44 stents) with BP-PtCr-EES or DP-CoCr-EES who underwent CAS at 1 year after stenting were investigated. We compared angioscopic findings assessed by angioscopy between BP-PtCr-EES (n=18) and DP-CoCr-EES (n=26). NIC grade and yellow plaque grade (YPG) was adopted from earlier reports from grade 0 to 3. We determined maximum (max-) and minimum (min-) NIC grade and heterogeneity score (HGS = max NIC grade minus min NIC grade). We also assessed YPG and the presence of thrombus (TH). Results Six lesions (33.3%) in BP-PtCr-EES group and 7 (26.9%) lesions in DP-CoCr-EES group were culprit lesions of acute coronary syndrome, which did not statistically differ between the two groups (p=0.74). And there were no significant differences in stent diameter (BP-PtCr-EES: 2.97±0.39 mm vs DP-CoCr-EES: 3.14±0.45 mm, p=0.22) and length (BP-PtCr-EES: 26.9±7.9 mm vs DP-CoCr-EES: 28.4±8.0 mm, p=0.54). In terms of CAS findings, BP-PtCr-EES group has better neointimal coverage than DP-CoCr-EES group (max NIC grade: 2.6±0.7 vs 2.0±0.9, p=0.01. min NIC grade: 1.1±0.8 vs 0.5±0.5, p&lt;0.01), but HGS was almost same (1.6±0.7 vs 1.5±0.9, p=0.70). YPG of BP-PtCr-EES group showed significantly lower than DP-CoCr-EES group (1.0±1.0 vs 1.7±1.0, p=0.02). The rate of TH was significantly lower in BP-PtCr-EES group than DP-CoCr-EES group (25%, n=6, vs 75%, n=18, p=0.03). There were no clinical events such as stent thrombosis or restenosis during the observation period in both stent groups. Conclusion Superior neointimal coverage and less YPG or TH were observed by CAS in the BP-PtCr-EES group at 1 year after stenting. Clinical significance was still unknown because of no clinical events in both groups. Prospective and large populations studies may be required. Funding Acknowledgement Type of funding source: None

Negative impact of ultra-thin strut on neointimal coverage condition within one year after implantation as compared to thin sturt in biogradable-polymer sirorimus eluting stents

Background BIOSCIENCE randomized trial which compared biodegradable-polymer sirolimus-eluting stents with ultra-thin (60μm) strut (ultra-thin BP-SES) and durable-polymer everolimus-eluting stents with thin (81μm) strut (thin DP-EES) have reported that definite stent thrombosis within 1 year had more frequently occurred in ultra-thin BP-SES (0.9%) than in thin DP-EES group (0.4%) although it was not statistically significant. It suggests that neointimal coverage after stent implantation within 1 year might be different between ultra-thin BP-SES and thin DP-EES. Recently, two types of biogradable-polymer sirorimus eluting stents, thin (80μm) strut type (thin BP-SES) and ultra-thin (60μm) strut type (ultra-thin BP-SES), can be available in clinical settings. Purpose We compared neointimal coverage conditions between ultra-thin BP-SES and thin BP-SES by optical coherence tomography (OCT). Methods Consecutive Forty-six patients who underwent 21 ultra-thin BP-SESs or 25 thin BP-SESs implantation were enrolled. We compared incidences of acute coronary syndrome, type B2/C lesion, atherectomy device use, stent size, stent length, maximum inflation pressure, and 8-month follow-up OCT parameters including proportions of uncovered struts (%Uncovered), malapposed struts, (%Mallaposed) and mean neointimal hyperplasia thickness (mean NHT) between the two groups. Results %Uncovered and %malapposed were significantly higher and mean NHT was significantly lower in ultra-thin BP-SES than in thin BP-SES (Table). The other parameters were similar between the two groups. Conclusion Ultra-thin BP-SES showed worse neointimal coverage as compared to thin BP-SES within 1 year after stent implantation, which may increase stent thrombosis. Funding Acknowledgement Type of funding source: None

Impact of diabetes mellitus on the early phase arterial healing after drug-eluting stent implantation: a multicenter coronary angioscopic study

Background Diabetes mellitus (DM) is a strong risk factor for major cardiac and cerebrovascular events. In particular, coronary artery disease with DM is often complicated with complex lesions. Drug-eluting stents (DES) are mainly used for these lesions, and dual-antiplatelet therapy (DAPT) has been used to prevent stent thrombosis. Early arterial healing after DES implantation may enable short DAPT strategy. However, the impact of DM on the arterial healing in the early phase has not been elucidated to date. Purpose We evaluated the arterial healing in the early phase after DES implantation using coronary angioscopy (CAS) and compared the findings between DM and non-DM patients. Methods This study was a multicenter retrospective observational study. We analyzed CAS findings of 337 lesions from 270 patients which were evaluated 3 to 5 months after DES implantation. Patients were divided into two groups: DM (149 lesions in 118 patients) versus non-DM groups (188 lesions in 152 patients). We assessed neointimal coverage (NIC) grades (maximum, minimum and dominant), thrombus adhesion and maximum yellow color of plaque underneath the stent. NIC was graded as follows: grade 0, stent struts were not covered; grade 1, stent struts were covered by thin layer; grade 2, stent struts were buried under neointima. Yellow color was graded as follows: grade 0, white; grade 1, light yellow; grade 2, yellow; grade 3, intensive yellow. Results Minimum NIC coverage grade was lower in DM group than in non-DM group (P=0.002, Figure), while maximum and dominant NIC coverage grades were similar between them (P=0.94 and P=0.59, respectively). Thrombus adhesion (44.3% versus 38.8%, P=0.32) and maximum yellow color grade (P=0.78) were also similar between DM and non-DM groups. Even after the adjustment by the confounding factors such as follow-up duration and primary disease of acute coronary syndrome, DM was an independent factor predicting grade 0 of minimum NIC (odds ratio [OR] 1.83 [95% confidence interval 1.11–3.03], P=0.019). Conclusion DM patients showed less covered struts than non-DM patients 3 to 5 months after DES implantation, suggesting that the recent ultra-short DAPT strategy might not be easily applicable to DM patients. Minimum neointimal coverage grade Funding Acknowledgement Type of funding source: None