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We established a methodology for initiating cross-linking of antibodies selectively on the cell surface through intermolecular copper-free click reactions facilitated by increased effective concentrations of antibodies binding to target antigens. Upon cross-linking of tetrazine- and bicyclononyne-modified trastuzumab on the surface of HER2-overexpressing cells, increased antibody uptake and activation of intracellular signaling were observed. Our findings demonstrate that the cross-linking reaction can significantly alter the biophysical properties of proteins, activating their unique functionalities on targeted cells to realize an increased cargo delivery and synthetic manipulation of cellular signaling.

Purpose: To improve the evaluation of low-attenuation plaque (LAP) by using semiautomated software and to assess whether the use of a proposed automated function (LAP editor) that excludes voxels adjacent to the outer vessel wall improves the relationship between LAP and the presence and size of the lipid-rich component (LRC) verified at intravascular US. At coronary CT angiography, quantification of LAP can improve risk stratification. Plaque, defined as the area between the vessel and the lumen wall, is prone to partial volume effects from the surrounding pericoronary adipose tissue., Materials and Methods: The percentage of LAP (%LAP), defined as the percentage of noncalcified plaque with an attenuation value lower than 30 HU (LAP/total plaque volume) at greater than or equal to 0 mm (%LAP 0 ), greater than or equal to 0.1 mm (%LAP 0.1 ), greater than or equal to 0.3 mm (%LAP 0.3 ), greater than or equal to 0.5 mm (%LAP 0.5 ), and greater than or equal to 0.7 mm (%LAP 0.7 ) inward from the vessel wall boundaries, were quantified in 155 plaques in 90 patients who underwent coronary CT angiography before intravascular US. At intravascular US, the LRC was identified by using echo attenuation, and its size was measured by using the attenuation score (summed score/analysis length) based on the attenuation arc (1 = < 90°, 2 = 90° to < 180°, 3 = 180° to < 270°, 4 = 270°-360°) for every 1 mm., Results: Use of LAP editing improved the ability for discriminating LRC (areas under receiver operating characteristic curve: 0.667 with %LAP 0 , 0.713 with %LAP 0.1 [ P < .001 for comparison with %LAP 0 ]), 0.778 with %LAP 0.3 [ P < .001], 0.825 with %LAP 0.5 [ P < .001], 0.802 with %LAP 0.7 [ P = .002]). %LAP 0.5 had the strongest correlation ( r = 0.612, P < .001) with LRC size, whereas %LAP 0 resulted in the weakest correlation ( r = 0.307; P < .001)., Conclusion: Evaluation of LAP at coronary CT angiography can be significantly improved by excluding voxels that are adjacent to the vessel wall boundaries by 0.5 mm. Supplemental material is available for this article. © RSNA, 2019., (2019 by the Radiological Society of North America, Inc.)

Objectives: We sought to evaluate the accuracy of standardized total plaque volume (TPV) measurement and low-density non-calcified plaque (LDNCP) assessment from coronary CT angiography (CTA) in comparison with intravascular ultrasound (IVUS)., Methods: We analyzed 118 plaques without extensive calcifications from 77 consecutive patients who underwent CTA prior to IVUS. CTA TPV was measured with semi-automated software comparing both scan-specific (automatically derived from scan) and fixed attenuation thresholds. From CTA, %LDNCP was calculated voxels below multiple LDNCP thresholds (30, 45, 60, 75, and 90 Hounsfield units [HU]) within the plaque. On IVUS, the lipid-rich component was identified by echo attenuation, and its size was measured using attenuation score (summed score ∕ analysis length) based on attenuation arc (1 = < 90°; 2 = 90-180°; 3 = 180-270°; 4 = 270-360°) every 1 mm., Results: TPV was highly correlated between CTA using scan-specific thresholds and IVUS (r = 0.943, p < 0.001), with no significant difference (2.6 mm 3 , p = 0.270). These relationships persisted for calcification patterns (maximal IVUS calcium arc of 0°, < 90°, or ≥ 90°). The fixed thresholds underestimated TPV (- 22.0 mm 3 , p < 0.001) and had an inferior correlation with IVUS (p < 0.001) compared with scan-specific thresholds. A 45-HU cutoff yielded the best diagnostic performance for identification of lipid-rich component, with an area under the curve of 0.878 vs. 0.840 for < 30 HU (p = 0.023), and corresponding %LDNCP resulted in the strongest correlation with the lipid-rich component size (r = 0.691, p < 0.001)., Conclusions: Standardized noninvasive plaque quantification from CTA using scan-specific thresholds correlates highly with IVUS. Use of a < 45-HU threshold for LDNCP quantification improves lipid-rich plaque assessment from CTA., Key Points: • Standardized scan-specific threshold-based plaque quantification from coronary CT angiography provides an accurate total plaque volume measurement compared with intravascular ultrasound. • Attenuation histogram-based low-density non-calcified plaque quantification can improve lipid-rich plaque assessment from coronary CT angiography.

We have developed a novel method to globally monitor the enzymatic activities of biological samples based on performing the global activity analysis on a proteome separated by native electrophoresis. The study of the alteration in peptide-metabolizing enzymatic activity in colorectal tumor specimens led us to the discovery of elevated thimet oligopeptidase activity, which contributed to the faster consumption of immune-stimulating peptide neurotensin.

Background: It has been shown that CT attenuation of noncalcified plaques depends on luminal contrast attenuation (LCA). Although tube potential (kilovolt [kV]) has been shown to exert influence on plaque attenuation through LCA as well as its direct effects, in-vivo studies have not investigated plaque attenuation at lower tube potentials less than 120 kV. We sought to evaluate the effect of kV and LCA on thresholds for lipid-rich and fibrous plaques as defined by intravascular ultrasound (IVUS)., Methods: CT attenuation of IVUS-defined plaque components (lipid-rich, fibrous, and calcified plaques) were quantified in 52 consecutive patients with unstable angina, who had coronary CT angiography performed at 100 kV (n = 25) or 120 kV (n = 27) using kV-adjusted contrast protocol prior to IVUS. CT attenuation of plaque components was compared between the two groups., Results: LCA was similar in the 100-kV and 120-kV groups (417.6 ± 83.7 Hounsfield Units [HU] vs 421.3 ± 54.9 HU, p = 0.77). LCA correlated with CT attenuation of lipid-rich (r = 0.49, p = 0.001) and fibrous plaques (r = 0.32, p < 0.05), but not with that of calcified plaques (r = 0.04, p = 0.81). When plaque attenuation was normalized to LCA, lipid-rich (0.087 ± 0.036, range -0.012-0.147) and fibrous plaque attenuation (0.234 ± 0.056, range 0.153-0.394) were distinct (p < 0.001) with no overlap for both kV groups. CT attenuation was not significantly different between 100-kV and 120-kV groups for lipid-rich (34.0 ± 21.5 vs 39.3 ± 12.9, p = 0.33) or fibrous plaques (95.4 ± 19.1 vs 97.6 ± 22.0, p = 0.75)., Conclusion: Plaque attenuation thresholds for non-calcified plaque components should be adjusted based on LCA. Further adjustment may not be required for different tube potentials., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI.

Aims: The aim of this study was to assess the incidence and impact on midterm outcomes of intimal versus subintimal tracking with both antegrade and retrograde approaches in patients undergoing successful percutaneous coronary intervention for chronic total occlusion (CTO)., Methods and Results: In 2012, a total of 1,573 CTO cases from 30 hospitals were enrolled in the Japanese CTO registry. Successful guidewire crossing was performed in 1,411 cases (89.7%). Among them, the guidewire penetration position was clearly identified using intravascular ultrasound (IVUS) imaging in 352 cases, and clinical follow-up at 12 months was performed in 323 cases. These 323 cases were enrolled in this retrospective study: 242 cases were treated with the antegrade approach (antegrade group) and 81 cases were treated with the retrograde approach (retrograde group). The endpoint of this study was target vessel revascularisation (TVR) and major adverse cardiac events (MACE) at 12-month follow-up. Subintimal tracking occurred more frequently in the retrograde group (11.6% vs. 30.9%, p<0.01). TVR was more frequent in the subintimal tracking group in the retrograde group (7.1% vs. 16.0%, p=0.03) but not in the antegrade group (2.8% vs. 3.6%, p=0.99). Although the occlusion length was similar, the subintimal tracking group required a longer stent length compared to the intimal tracking group in the retrograde approach (59.7±24.4 mm vs. 74.0±24.4 mm, p<0.01)., Conclusions: Subintimal tracking was more frequent in the retrograde approach. Intimal tracking should be recommended in the retrograde approach to reduce stent length and to improve follow-up outcomes.

When patients who have previously undergone coronary artery bypass graft surgery develop ischemia symptoms that cannot be controlled by optimal medical therapy, repeat revascularization is indicated. The revascularization strategy should be based on individual clinical and anatomical characteristics. We report here a challenging patient who presented with recurrent stable angina due to worsening of a proximal right coronary artery (RCA) stenosis to chronic total occlusion (CTO) after anastomosis of the right gastroepiploic artery (GEA) to the posterior descending artery. A soft guidewire was advanced through the right GEA collateral channel to the distal end of the CTO, but the dedicated CTO guidewires could not be advanced across the severely calcified CTO using the retrograde wire crossing or kissing wire techniques. The RCA was eventually revascularized by implantation of drug-eluting stents using the intravascular ultrasound-guided reverse controlled antegrade and retrograde subintimal tracking technique.

Surgeons currently use two different wire-based approaches to recanalize coronary chronic total occlusion (CTO): antegrade and retrograde. It has been demonstrated that the retrograde approach has improved the procedural success rate, but it remains unclear whether the retrograde approach is better than the antegrade approach for the long term. In this study, we enrolled a total of 187 patients with a diagnosis of CTOs. We evaluated the baseline characteristics of these patients and performed percutaneous coronary intervention to treat their problems by using either antegrade or retrograde approaches and different techniques in both groups. In the antegrade approach, we used three techniques: single wire, parallel wire, and side branch. The techniques in retrograde included kissing wire, controlled antegrade and retrograde subintimal tracking (CART), and reverse CART. We found that the antegrade and retrograde groups had similar baseline characteristics, with a few minor differences. Most importantly, we found that within 1 yr of the recanalizing procedure, the restenosis rate and major adverse cardiac event rate of the retrograde group were significantly higher compared to the antegrade group. We conclude that the retrograde approach may not be as beneficial as the antegrade approach for long-term clinical outcomes.

A single coronary artery (SCA) arising from the sinus of Valsalva and supplying the entire heart is a rare congenital anomaly. According to the modified Lipton's classification, R-1 is by far the most rare subtype of SCA, with an incidence of 0.0008% in patients undergoing coronary angiography. We present a case with an unreported anomaly, classified as Lipton R-I subtype, which initially followed the normal course of the right coronary artery. The posterior descending artery then proceeded as the distal and middle sections of the left anterior descending artery, while the posterolateral branch proceeded as the left circumflex artery and finally terminated as the proximal left anterior descending artery. The patient underwent percutaneous intervention in the posterolateral branch for an acute coronary syndrome.

Background: TAFRO syndrome is a unique clinicopathologic variant of multicentric Castleman's disease that has recently been identified in Japan. It is characterized by a constellation of symptoms: Thrombocytopenia, Anasarca, reticulin Fibrosis of the bone marrow, Renal dysfunction and Organomegaly (TAFRO). Previous reports have shown that affected patients usually respond to immunosuppressive therapy, but the disease sometimes has a fatal course. TAFRO syndrome occurs in the middle-aged and elderly and there are no prior reports of the disease in adolescents. Here we report the first adolescent case, successfully treated with anti-IL-6 receptor antibody (tocilizumab, TCZ) and monitored with serial cytokine profiles., Case Presentation: A 15-year-old Japanese boy was referred to us with fever of unknown origin. Whole body computed tomography demonstrated systemic lymphadenopathy, organomegaly and anasarca. Laboratory tests showed elevated C-reactive protein and hypoproteinemia. Bone marrow biopsy revealed a hyperplastic marrow with megakaryocytic hyperplasia and mild reticulin fibrosis. Despite methylprednisolone pulse therapy, the disease progressed markedly to respiratory distress, acute renal failure, anemia and thrombocytopenia. Serum and plasma levels of cytokines, including IL-6, vascular endothelial growth factor, neopterin and soluble tumor necrosis factor receptors I and II, were markedly elevated. Repeated weekly TCZ administration dramatically improved the patient's symptoms and laboratory tests showed decreasing cytokine levels., Conclusion: To our knowledge, this is the first report of TAFRO syndrome in a young patient, suggesting that this disease can occur even in adolescence. The patient was successfully treated with TCZ. During our patient's clinical course, monitoring cytokine profiles was useful to assess the disease activity of TAFRO syndrome.

The approach to a chronic total occlusion (CTO) still remains one of the most technical challenges in percutaneous coronary intervention (PCI). CTO lesions with a blunt entry point, calcification, and failure of a previous approach, are the independent predictors of CTO-PCI failure. Here we report a successful antegrade approach for reattempted CTO-PCI of a left anterior descending artery (LAD) with unknown, calcified ostium. We used a novel side branch cutting technique, combined with intravascular ultrasound-guided wiring and parallel wire techniques. Considering the ramus artery as a side branch and dilating it with a cutting balloon was a crucial part of the strategy for achieving overall procedural success using this approach. This is the first report describing a side branch cutting technique in CTO-PCI. The combined application of multiple antegrade techniques, using the latest devices, might provide an effective and safe approach for complex CTO-PCI.

Recently, subintimal angioplasty has been introduced as a bailout strategy to improve the success rate of PCI for vessels with CTO. However, the long-term outcome of subintimal angioplasty has not been determined, and a limitation of subintimal angioplasty is the uncertainty in making the re-entry point. We report two cases, where occlusive in-stent restenosis occurred in a stent implanted in the subintimal space of the RCA that had CTO. These two cases were successfully treated with bypass restenting across the struts of an occluded subintimal stent using a retrograde approach. A retrograde wire crossed the occluded segment through the lumen along the outside of the stent and reentered the inside of the stent across the stent struts. The reverse CART technique followed by multiple restenting across the stent struts restored antegrade flow. Follow-up angiography demonstrated the patency of the RCA., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Controlled antegrade and retrograde subintimal tracking (CART) or reverse CART techniques is the final step for percutaneous revascularization of coronary chronic total occlusion (CTO), but it still represents technical challenges and risk in interventional procedures., Objectives: Our purpose was to utilize intravascular ultrasound (IVUS)-guided reverse CART approach for percutaneous revascularization of CTO in our heart center, focusing on its safety, efficacy, and latest technical developments., Methods: From November 2006 to November 2012, 49 patients with CTO failed to antegrade and/or retrograde percutaneous revascularization of CTO from true lumen to true lumen were enrolled in and underwent IVUS guided reverse CART approach., Results: The mean J-CTO score of cases was 2.5. IVUS guidance was successfully implemented in 95.9%; IVUS identified that 61.7% of retrograde wires were located at intimal space, and 59.5% of antegrade wires were located at subintimal space. A Corsair channel dilator was used in 77.6% of cases. The success rates of technique and procedure were 95.9% and 93.9%, respectively; the technical minor complications were observed in 10.2% of cases, without significant clinic outcomes; 2.0% of cases occurred with a major adverse cardiac event of non-ST-elevation myocardial infarction; and no case occurred with target vessel revascularization or death. The mean length of stent implanted in a single CTO vessel was 51.3 mm. No patient appeared with radiation dermatitis and contrast-induced rise of creatinine., Conclusions: IVUS guided reverse CART approach is effective and safe for percutaneous revascularization of complex CTO, with a high success and a low complication rate. It is feasible to develop this approach for percutaneous revascularization of complex CTO. However, suitable case selection and lately device handling by experienced operators are the crucial points of success., (© 2013, Wiley Periodicals, Inc.)

Background: Provisional crossover stenting has the potential risk of side-branch (SB) compromise, which may result in periprocedural myocardial infarction. Predilatation is a useful technique to prevent SB compromise., Objectives: The aim of this study was to assess the safety and efficacy of predilatation using the kissing-balloon technique (preKBT) during provisional crossover stenting compared with sequential predilatation on clinical outcomes in true coronary bifurcation lesions., Methods: We retrospectively evaluated 204 consecutive non-left main true bifurcation lesions (182 patients) in whom provisional crossover stenting was performed with preKBT (preKBT group, n = 144) or sequential predilatation (sequential group, n = 60) from March 2006 to February 2012., Results: There were 30 lesions (20.8%) in the preKBT group that developed SB ostial dissection compared with 8 lesions (13.3%) in the sequential group (P=.241). There was no SB flow impairment or SB access failure due to SB ostial dissection. SB compromise (Thrombolysis in Myocardial Infarction <3) immediately after crossover stenting occurred in 5 lesions (3.5%) in the preKBT group versus 7 lesions (11.7%) in the sequential group (P=.043). Major adverse cardiac events at 6-8 months of follow-up were observed in 5 lesions (3.5%) in the preKBT group versus 8 lesions (13.3%) in the sequential group (P=.022)., Conclusions: Regardless of more complex bifurcation lesions in the preKBT group, preKBT successfully prevented SB compromise due to crossover stenting without unfavorable complications and improved the mid-term clinical outcome compared with sequential PTCA in patients with non-left main, true coronary bifurcation lesions.

Objective: To clarify the impact of off-label use of drug-eluting stent (DES) on 5-year outcomes., Background: Studies on the outcomes of on- vs. off-label use of DES have been limited by the duration of observation., Methods: We analyzed 1937 patients from a multicenter registry that includes 95% of patients with 5-year follow-up data. We defined 10 variables as off-label indications according to the manufacturer's instructions for use, and 1665 of 1937 patients (86.0%) met the criteria for at least 1 off-label indication., Results: At 5 years, there were no differences in the rates of death, myocardial infarction (MI), and stent thrombosis between off-label and on-label use. The frequency of major adverse cardiac events (MACE), target lesion revascularization (TLR), non-TL but target vessel revascularization (TVR), and target vessel failure were higher in the off-label only during the first year. Among the off-label, having 2 indications was associated with TVR hazard ratio (HR) 1.62; 95% confidence interval (95%CI), 1.09-2.36 and TLR (HR, 1.90; 95%CI, 1.30-2.85). Moreover, having ≥3 off-label indications increased the risk of MACE (HR, 1.70; 95% CI, 1.23-2.40) compared with on-label use. Thrombosis rates increased with the number of off-label indications; it was 0.32% with 1, 0.69% with 2, and 3.54% with ≥3 off-label indications (p<0.001). This trend was also seen with other outcomes, except for non-TL TVR. Patients with ≥3 off-label indications had a remarkably different clinical course., Conclusion: Off-label use did not increase rates of death and MI as compared with on-label use, but the number of off-label indications influenced outcomes at 5 years., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

We experienced a rare case in which a guidewire was advanced into a coronary vein through an arteriovenous fistula caused by wire perforation. The patient, who had chronic total occlusion (CTO) of the left circumflex coronary artery, was treated successfully with a procedure guided by intravascular ultrasound (IVUS). The IVUS-guided parallel-wire technique allowed recrossing of the guidewire into the distal true lumen of the CTO by identifying the anatomy of the occluded segment and the appropriate re-entry point. Angiography demonstrated that the fistula was completely sealed after stent deployment, and there was no extravasation.

Background: Long-term outcome and safety concerns regarding drug-eluting stents (DES) for acute myocardial infarction (AMI) treatment is still debated., Methods and Results: We analyzed data from 1937 patients with complete 5-year follow-up (94.5%) from a multicenter registry of sirolimus-eluting stents (J-PMS). The patients were divided into 2 groups: AMI (n=133) and non-AMI (n=1804) by clinical presentation of index procedure, and compared the outcomes. At 5-year follow-up, there were no significant differences in major adverse cardiac events (MACE), death, MI, or stent thrombosis between the groups. However, target vessel related events (TVF; revascularization, cardiac death, MI, thrombosis) were higher in the non-AMI group (p=0.03). In the early phase (0-6 months), MACE and death/MI were higher in the AMI group (6.0% vs. 3.0%; p=0.02 and 6.8% vs. 2.1%; p<0.001). However, in the late phase (6-60 months), there was a difference in TVF between the 2 groups, with a steady increase in the non-AMI group (p=0.03). Over 60% of patients with AMIs were started on dual antiplatelet therapy after stent implantation or on the same day. However, dual anti-platelet therapy duration was similar (867 ± 18 days in the AMI and 727 ± 57 days in the non-AMI group, p=0.5). Frequency of bleeding was similar., Conclusion: Five-year observation of AMI treatment using drug-eluting stent compared with non-AMI has no clinical disadvantage., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the risks and benefits of prolonged dual antiplatelet therapy (DAPT: thienopyridine plus aspirin) following placement of drug-eluting stents (DES). The optimal duration of DAPT is not well established., Methods: We analyzed a prospective registry of 2,050 patients with sirolimus-eluting stents during a 5-year follow-up. We divided 1,691 patients into two groups according to DAPT duration (DAPT ≤12 months (n=749) and DAPT >12 months (n=942)) and compared the clinical outcomes using a landmark analysis., Results: The frequencies of major adverse cardiac events (MACE: 15.6% vs. 18.2%), death (10.0% vs. 11.5%), myocardial infarction (2.3% vs. 2.1%), target lesion revascularization (4.5% vs. 6.3%) and stent thrombosis (0.8% vs. 0.8%) were similar between the two groups. However, the frequency of bleeding was higher in the DAPT >12 months group (1.1% vs. 2.6%, p=0.030). The adjusted 12-month landmark analysis showed no differences in the incidence of MACE (hazard ratio (HR) 0.892; 95% confidence interval (CI) 0.689-1.155; p=0.385) or a composite of target vessel revascularization, cardiac death and myocardial infarction (target vessel failure: HR 0.922; 95% CI 0.678-1.255; p=0.606). There were no differences in the frequency of stent thrombosis between the two groups during years 2 to 5 after stenting; however, with regard to bleeding, an increase in the frequency of hemorrhage events was observed after four years from the index procedures in the DAPT >12 months group., Conclusion: DAPT performed beyond 12 months is associated with increased an frequency of bleeding complications and does not prevent the incidence of MACE, including stent thrombosis, during five years of follow-up after sirolimus-eluting stent implantation. Conducting larger, randomized studies will therefore be needed to confirm this finding.

Background: The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid., Methods and Results: Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121 ± 17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change., Conclusion: Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.

The long-term outcome and compliance of dual-antiplatelet therapy after implantation of drug-eluting stent in the "real world" setting in Japan has not been well investigated. The purpose of this study was to provide information on the introduction and outcomes including status and compliance of dual-antiplatelet therapy of sirolimus-eluting stent (SES). Five-year follow-up was achieved in 1937 of 2050 patients (94.5%). Off-label use was 87.3% in this study. The incidence of MACE was 23.2%, including death (13.4%), MI (3.4%), and target lesion revascularization (TLR, 9.6%). Multivariate analysis for TLR predicted dialysis [hazard ratio (HR) 3.5, 95% confidence interval (CI) 2.13-5.93], lesion length >30 mm (HR 1.89, 95% CI 1.24-2.84), vessel diameter <2.5 mm (HR 1.55, 95% CI 1.10-2.18), ostial lesion (HR 1.59, 95% CI 1.10-2.31), and previous PCI (HR 1.42, 95% CI 1.00-2.00). There were 25 events of definite/probable thrombosis. Very late thrombosis was identified in 17 cases, and the slope of the linear portion of the cumulative incidence curve of stent thrombosis was 0.28% per year. Seven of the 17 events (41.2%) occurred under dual anti-platelet therapy. Five-year outcomes after SES implantation in the "real world" in Japanese showed that dialysis, previous PCI, small vessel <2.5 mm, long lesion >30 mm, and ostial lesions were the predictors of TLR at 5-years. Stent thrombosis rate was lower than previous reports.

Background: The 64-multislice computed tomography (MSCT) can be used to directly guide the complex percutaneous coronary intervention (PCI) procedure and predict the outcome. This study aimed to determine the possibility of success of angioplasty for chronic total occlusion (CTO) performed on the basis of MSCT results., Methods: In this study, we assessed 82 de novo CTO lesions in 67 patients, who were subjected to 64-MSCT before undergoing PCIs. The lesions were either treated with an antegrade approach or a combined bilateral antegrade and retrograde approach. The clinical characteristics of the patients and the angiographic and 64-MSCT parameters associated with the intervention result were analyzed., Results: In this study, the technical and procedural success rates were 89.0% and 80.5%, respectively. There were significant differences in heavy calcification with the calcification length ratio of >0.5, proximal stump calcification, and distal stump calcification between the technical-success and technical-failure groups (P<0.001, P=0.022, and P=0.003, respectively) as well as between the procedural-success and procedural-failure groups (P<0.001, P=0.042, and P=0.014, respectively). Multivariate analysis showed that heavy calcification was the strong independent parameter that not only influenced technical success (odds ratio [OR]=0.040, 95% confidence interval [CI]=0.006-0.254, P=0.001) but also procedural success (OR=0.127, 95% CI=0.035-0.461, P=0.002)., Conclusions: Calcification length ratio of >0.5 remains to be the independent negative predictor of both technical and procedural success., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

This is the case of an 85-year-old woman, who developed a large aneurysm of the saphenous vein graft to the left circumflex coronary artery with a fistulous communication to the left atrium (LA) after being asymptomatic for 18 years post-coronary artery bypass graft surgery. She suffered from recurrent congestive heart failure due to the extra abnormal flow and pressure overload to the LA. Because of high risk of re-operation, we performed a combined treatment of trans-catheter coil embolization and modified covered stent implantation. After successful treatment, cardiac multi-slice computed tomography revealed almost completely decreased trans-fistulous flow to the LA.

Aims: Long-term outcomes after sirolimus-eluting stent (SES) implantation in haemodialysis (HD) patients have remained controversial. We investigated the impact of HD on outcomes after SES implantation., Methods and Results: We analysed the data on 2050 patients who underwent SES implantation in a multi-centre prospective registry in Japan. Three-year clinical outcomes were compared between the HD group (n = 106) and the non-haemodialysis (NH) group (n = 1944). At the 3-year clinical follow-up, the rates of unadjusted cardiac mortality (HD: 16.3 vs. NH: 2.3%) and target-lesion revascularization (TLR) (HD: 19.4 vs. NH: 6.6%) were significantly higher in the HD group than the NH group (P < 0.001). Although HD group had a numerically higher stent thrombosis rate, the difference in stent thrombosis between the two groups (HD: 2.0 vs. NH: 0.7%) did not reach statistical significance. Using Cox's proportional-hazard models with propensity score adjustment for baseline differences, the HD group had higher risks of TLR [HD: 16.3 vs. NH: 6.1%; hazard ratio, 2.83; 95% confidence interval (CI): 1.62-4.93, P = 0.0003] and cardiac death (HD: 12.3 vs. NH: 2.3%; hazard ratio, 5.51; 95% CI: 2.58-11.78, P < 0.0001). The consistent results of analyses, whether unadjusted or adjusted for other baseline clinical and procedural differences, identify HD as an independent risk factor for cardiac death and TLR., Conclusions: Percutaneous coronary intervention with SES in HD patients has a higher incidence of repeat revascularization and mortality compared with those in NH patients. Haemodialysis appears to be strongly associated with mortality and repeat revascularization even after SES implantation.

Background: Long-term outcomes of patients with bifurcated lesions and the restenotic response of the side branches after sirolimus-eluting stent (SES) implantation, comparing 1-stent with 2-stent treatment, are still under discussion., Methods and Results: Japan Post-Marketing Surveillance Registry (J-PMS) is a prospective registry designed to evaluate the safety and efficacy of the SES in routine clinical practice. Angiograms of 1,063 patients with 1,250 lesions were analyzed at the independent core lab. Of these, 324 patients with bifurcation lesions were enrolled. Clinical endpoints were assessed at 3 years. Both main and side branches were evaluated by quantitative coronary angiography at post-procedure (n=349) and 8-month follow up (n=293). Two-stent treatment was performed in 12% of the cases. In-segment restenosis rates at 8 months were 25.6% in the side branch, but newly developed restenosis was seen in only 6.8%. Late loss at the carina of the side branch was -0.11mm in the 1-stent group. Major adverse cardiovascular events rate was 18.3% at 3 years. Target-lesion revascularization rate up to 3 years was 21.6% in the 2-stent group and 8.7% in the 1-stent group (P=0.037). Stent thrombosis occurred in 6 cases (2.0%) until 3 years. Of these, 4 cases were treated with 2-stent (10.81% vs. 0.76% in 1-stent, P=0.003, respectively)., Conclusions: In a real-world setting, treatment of coronary bifurcation lesions using SES demonstrated favorable long-term outcomes as long as the side branch was not stented.

Recently, drug-eluting stent (DES) has been recommended as the first choice in those patients who need stent implantation in unprotected left main coronary artery (ULMCA) stenosis. However, the long-term safety and efficacy of this procedure is still controversial. The objective of this study was to evaluate the safety and efficacy of bare metal stent (BMS) implantation in ULMCA stenting in the DES era. We implanted BMS (mainly 4 mm-diameter) in large-sized ULMCA after December 2004 when DES became available. The results of BMS implantation (n = 19) were compared with those of DES implantation (n = 39). There was no significant difference between the 2 groups regarding age, gender and coronary risk factors. Emergency procedures were more frequently performed in the BMS group than in the DES group (53% vs. 26%, p = 0.08). The initial mortality was 10.5% (n = 2) in the BMS group and 2.6% (n = 1) in the DES group (p = 0.25). There was no stent thrombosis, Q-wave myocardial infarction or emergent bypass surgery in either group during their hospital stay. The restenosis rate was 0% (n = 45) in both groups, and the target vessel revascularization rate was 5.9% in the BMS group (1/17) and 2.6% (1/38) in the DES group (p = 0.53). Therefore, there were no statistically significant differences in outcomes between the two study groups. These results indicate that BMS implantation in a large-sized ULMCA may be a safe and effective treatment even in the DES era.

Objectives: The goal of this study was to compare the antegrade-approach and bilateral-approach strategies for chronic total occlusion (CTO)., Background: The retrograde approach has been reported for difficult CTO lesions., Methods: This study assessed 96 consecutive patients with 119 CTO lesions. The lesions were treated with either an antegrade approach (A group) or a combined bilateral antegrade and retrograde approach (B group). The specific intervention techniques, in-hospital success rate, and major adverse cardiac and cerebrovascular events (MACCE) were compared., Results: Lesions with well-developed septal collaterals with nontortuous microchannels were preferentially chosen for the B group versus A group (P < 0.001 and 0.008, respectively). Compared with the A group, there were more CTO lesions located in the right coronary artery in the B group (P < 0.001). In the B group, the CTO lesions had a longer length and needed stiffer wires for crossing than in the A group (P = 0.001 and 0.046, respectively). The technical success rate was 94% and 86% for the A group and the B group, respectively (P = 0.127). In-hospital complications were not different between the two groups. The B group needed a higher radiation exposure dose and a greater exposure time than the A group (P < 0.001). In the B group, use of the retrograde method significantly increased the final success rate., Conclusions: These results suggest that all CTO lesions should first be managed with an antegrade approach. When there is difficulty crossing the lesion, switching to a bilateral approach is an option for lesions with well-developed collaterals.

Background: Clinical data of sirolimus-eluting stent (SES) implantation are under investigation in Japan., Methods and Results: The CYPHER stent Japan Post-Marketing Surveillance Registry (J-PMS) was conducted at 50 medical centers to assess the results of SES in daily clinical practice exclusively under aspirin plus low dose ticlopidine (200 mg/day). A total of 2,459 lesions in 2,054 patients were treated with 3,285 SES. The mean age was 67.1 +/-10.1 years, 75.6% were men and 43.3% were diabetics. Intravascular ultrasound was used in 77.2%. The 8-month angiographic and 1-year clinical follow-up data were available in 85.4% and 96.8%, respectively. Quantitative coronary angiography showed the reference vessel diameter and percentage diameter stenosis at baseline were 2.47 +/-0.58 mm and 72.0 +/-16.1%. The 8-month late loss was 0.20 +/-0.50 mm. The major adverse cardiovascular events at 1 year was 7.3%; cardiac death: 1.1%, myocardial infarction (MI): 1.2%, and target lesion revascularization (TLR): 4.2%. The rates of definite and probable stent thrombosis at 1 year were 0.30% and 0.10%, respectively. Hemodialysis was the strongest predictor of death/MI or TLR., Conclusions: J-PMS showed the effectiveness of SES implantation under aspirin plus low dose ticlopidine administration at 1 year, although further studies are necessary to demonstrate the safety.

We analyzed 14 cases of new lesions inside implanted bare-metal stents. In every case, there was no angiographic restenosis within 3 years, but a new lesion was observed inside a stented segment at long-term follow-up (>5 years). Fourteen cases were evaluated: 9 with Wiktor stents, 2 with Palmaz-Schatz stents, and 3 with ACS Multilink stents. The interval from stent implantation to follow-up angiography was 63-147 months (89 +/- 23). Thirteen lesions were treated by percutaneous coronary intervention (PCI) and stenotic tissue was obtained by directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were composed of newly developed atherosclerosis facing the healed neointimal layer, and four samples showed histopathological findings of acute coronary syndrome. Stent struts were retrieved in four cases and no inflammation was observed surrounding them. Qualitative and quantitative analysis of stent struts was performed in two cases that showed no metal corrosion. These findings suggest that new atherosclerotic progression occurred inside the implanted stent without peristrut inflammation.

Nitric oxide (NO) plays an important role in controlling the physiological functions of the cardiovascular system. However, toxic peroxynitrite is produced by the reaction of NO with superoxide. We investigated the effect of aged garlic extract (AGE) on NO production, and on oxidative stress induced by peroxynitrite. A single dose of AGE temporarily increased NO production by 30-40% between 15 and 60 min after administration to mice. The time course of the fluctuation in NO levels in the AGE-treated group clearly differed from that in a group treated with an inducible NO synthase (iNOS) inducer. A selective constitutive NOS (cNOS) inhibitor overcame the effect of AGE. These results indicate that AGE increases NO production by activating cNOS, but not iNOS. In another experiment, the addition of AGE to a rat erythrocyte suspension reduced the rate of peroxynitrite-induced hemolysis in a concentration-dependent manner, suggesting that AGE protects erythrocytes from membrane damage induced by peroxinitrite. Because an increase in NO derived from cNOS and protection against peroxynitrite are important factors in the prevention of cardiovascular disease, our data strongly suggest that AGE could be useful in preventing cardiovascular diseases associated with oxidative stress or dysfunctions of NO production.

A unique garlic preparation, aged garlic extract (AGE), was examined for its modifying effect on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats, using the medium-term bioassay system based on the 2-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular foci. GST-P-positive foci were significantly decreased in rats treated with AGE at doses of 2, 5, and 10 mL/kg, i.g., 5 times per week during the promotion phase. In addition, to clarify the mechanism underlying the inhibitory effect of AGE, the effect of AGE on hepatocellular proliferation was evaluated using partially hepatectomized rats as a liver-regeneration model. The bromodeoxyuridine-labeling indices in the livers of the AGE group were significantly lower than those in the control group at 24 h, the maximum proliferation period after partial hepatectomy. These findings indicate that AGE inhibited the development of putative preneoplastic lesions in rat hepatocarcinogenesis, involving a slowing in the proliferation rate of liver cells after partial hepatectomy.