This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m2; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.

The purpose of this study was to evaluate the initial and long-term outcomes of Percutaneous Transluminal Angioplasty (PTA) for central venous stenosis or occlusion in chronic hemodialysis patients. A total of 363 central venous lesions (277 stenosis and 86 occluded lesions) of 146 patients were enrolled and analyzed retrospectively; these included 130 de novo lesions and 233 restenosis lesions. The procedural success rate in our cohort was 97.0% (352/363 lesions); success rate for stenosis was significantly higher than that for occluded lesions (99.3% vs. 89.5%, P < 0.001). Complications during PTA procedures occurred in nine lesions (2.5%); however, there were no serious complications. A total of 120 stents were implanted for 111 lesions; the rate of stent placement for occluded lesions was significantly higher than that for stenosis lesions (68.8% vs. 18.4%, P < 0.001). The primary patency of de novo lesions was significantly higher than that of restenosis lesions (P = 0.0004); the assisted patency of de novo lesions at 12 and 36 months were 94.4% and 89.0%, respectively. There was no significant difference of primary patency between balloon angioplasty and stent placement for de novo lesions, however, primary patency after stent placement for restenosis lesions was significantly higher than that after balloon angioplasty (P = 0.001). In conclusion, PTA for central venous stenosis or occlusion was safe procedure with low rate of technical failure. The patency of vascular access in long-term was maintained by the repeated intervention. Stent placement could help prolong the patency period for restenosis lesions.

Subclinical peripheral artery disease (PAD) might be associated with pathophysiology of contrast-induced acute kidney injury (CI-AKI). We hypothesized that concomitant PAD in patients with the acute coronary syndrome (ACS) would represent a high-risk subgroup with a greater incidence of CI-AKI, both of which lead to higher mortality after percutaneous coronary intervention (PCI). Six hundred and seventy-five consecutive patients with ACS who underwent PCI and examination of ankle-brachial index (ABI) were analyzed retrospectively. The presence of PAD was defined as an ABI < 0.9. We investigated whether (1) PAD was an independent predictor of CI-AKI (≥ 0.3 mg/dL or ≥ 50% relative increase in serum creatinine within 48 h after PCI) and (2) PAD and CI-AKI were independently associated with long-term mortality. Of the 675 patients with ACS, 114 (17%) exhibited PAD. The incidence of CI-AKI was significantly higher in PAD patients, compared with the remaining patients (12% vs. 4%, p < 0.001). Multivariate logistic regression analysis revealed that the presence of PAD was an independent predictor for the development of CI-AKI [odds ratio 2.50, 95% confidence interval (CI) 1.07–5.73, p < 0.05]. During the median 4-year follow-up, there were 65 incidents of all-cause death. In the multivariate Cox proportional hazard regression analysis, the presence of PAD [hazard ratio (HR) 2.08, 95% CI 1.17–3.65, p < 0.05] and CI-AKI (HR 2.23, 95% CI 1.08–4.26, p < 0.05) were associated with an increased risk of all-cause mortality. Assessment of ABI provides useful information for predicting CI-AKI and long-term mortality in patients with ACS after PCI.

Background: Although concomitant peripheral artery disease in patients with acute coronary syndrome (ACS) has been considered as a high-risk subgroup with a greater incidence of bleeding after percutaneous coronary intervention (PCI), few data exist regarding the clinical utility of the ankle brachial index (ABI) for predicting bleeding complications, which affects the subsequent outcome. Methods: Eight hundred and twenty-four consecutive patients with ACS who underwent PCI and ABI examination were analyzed retrospectively. Decreased-ABI was defined as ABI <0.9. The primary outcome was bleeding complications within 30 days, which was defined according to the Bleeding Academic Research Consortium classification grade >= 3. The secondary endpoint was all-cause death during follow-up. Results: Of the 824 patients with ACS. 137 (16.6%) exhibited decreased-ABI. The incidence of bleeding complications was significantly higher in patients with decreased-ABI, compared with the remaining patients (21.9% vs. 6.0%, p < 0.001). In multivariate analysis, anemia [odds ratio (OR) 2.14], estimated glomerular filtration rate < 60 mL/min/1.73 m(2) (OR 2.14), femoral access (OR 3.31), use of an intra-aortic balloon pump (OR 3.16), and decreased-ABI (OR 2.58) were independent predictors of 30-day bleeding complications. Assigning 1 point for each variable, we developed a new bleeding risk score (range, 0-5). The area under the receiver-operating characteristic curve for the probability of 30-day bleeding for the new risk score was significantly superior than that of the traditional one (0.82 vs. 0.76, p < 0.05). During the median 4-year follow-up, there were 98 incidents of all-cause death, Multivariate Cox-proportional hazard analysis revealed that decreased-ABI [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.15-3.13, p < 0.05] and 30-day bleeding (HR 3.00, 95% CI 1.76-4.97, p < 0.001) were associated with an increased risk of all-cause mortality. Conclusions: Assessment of ABI provides useful information for predicting 30-day bleeding complications and long-term mortality in patients with ACS after PCI. (C) 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Background: The comparative tolerability, efficacy, and safety of bisoprolol and carvedilol have not been established in Japanese patients with heart failure and reduced ejection fraction (HFrEF). Methods and Results: The CIBIS-J trial is a multicenter, open-label, non-inferiority randomized controlled trial of bisoprolol vs. carvedilol in 217 patients with HFrEF (EF <= 40%). The primary endpoint was tolerability, defined as reaching and maintaining the maximum maintenance dose (bisoprolol 5 mg/day or carvedilol 20 mg/day) during 48 weeks of treatment. The primary endpoint was achieved in 41.4% of patients in bisoprolol (n=111) and 42.5% in carvedilol (n=106) groups. The non-inferiority of tolerability of bisoprolol compared with carvedilol was not supported, however, neither beta-blocker was superior with regard to tolerability. Heart rate (HR) decreased in both groups and its decrease from baseline was significantly greater in the bisoprolol group (20.3 vs. 15.4 beats/min at 24 week, P<0.05). Plasma B-type natriuretic peptide (BNP) levels decreased in both groups and the decrease was significantly greater in the carvedilol group (12.4 vs. 39.0 % at 24 weeks, P<0.05). Conclusions: There were no significant differences between bisoprolol and carvedilol in the tolerability of target doses in Japanese HFrEF patients. The clinical efficacy and safety were also similar despite the greater reduction in HR by bisoprolol and plasma BNP by carvedilol.

Aim: The prospective, randomized, multicenter Myocardial Ischemia Treated with Percutaneous Coronary Intervention and Plaque Regression by Lipid Lowering & Blood Pressure Controlling assessed by Intravascular Ultrasonography (MILLION) study demonstrated that combined treatment with atorvastatin and amlodipine enhanced coronary artery plaque regression. Although the baseline high-sensitive C-reactive protein (hs-CRP) reportedly plays an important role in atherogenesis, few data exist regarding the relationship between hs-CRP and plaque regression in patients receiving a combined atorvastatin and amlodipine therapy. Methods: A total of 68 patients (male, 55; mean age, 64.2 years) with baseline and follow-up 3-dimensional intravascular ultrasound examinations in the MILLION study were stratified by baseline hs-CRP level quartiles. The serial measurements of lipid, blood pressure, and percentage changes in the plaque volume were compared between the groups, and the factors associated with the percentage change in the plaque volume were assessed. Results: There were no significant between-group differences in the extent of change in low-density lipoprotein cholesterol (LDL-C) or systolic and diastolic blood pressure after 18-24 months of treatment. The percentage change in the plaque volume showed a linear association with the baseline hs-CRP (p for trend < 0.05); however, there was no correlation with changes in LDL-C or systolic and diastolic blood pressure. In the multiple regression analysis, the baseline hs-CRP level was independently associated with the percentage change in the plaque volume (beta = 0.29, p = 0.022). Conclusions: Coronary plaque regression was associated with the baseline hs-CRP level in patients treated with a combined lipid- and blood pressure-lowering therapy.

Pharmacologic treatment of acute coronary syndromes 765an early switch from prasugrel to clopidogrel was recently identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).Of note, differences in antiplatelet drug response in smokers and non-smokers were reported in prior studies and clinical outcomes of ACS patients undergoing PCI depend on smoking status.Thus, the safety and efficacy of any DAPT de-escalation strategy may differ in relation to smoking status.Purpose: This post-hoc analysis of the TROPICAL-ACS trial aimed to assess the impact of smoking on clinical outcomes following guided de-escalation of DAPT in ACS patients.Methods: The multicentre TROPICAL-ACS trial randomised 2610 biomarkerpositive ACS patients 1:1 to either standard treatment with prasugrel for 12 months (control group) or a platelet function testing (PFT) guided de-escalation of DAPT.For this post-hoc analysis, we used univariate and multivariate Cox proportional hazards models to assess the association and interaction of smoking status on clinical endpoints across study groups.Results: In non-smokers (n=1428) a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to BARC criteria) compared to control group patients (7.9% vs. 11.0%;HR 0.71, 95% CI 0.50-0.99,p=0.048).Current smokers (n=1182) showed similar event rates between study groups (6.6% vs. 6.6%;HR 1,95% CI 0.64-1.56,p>0.99; see Figure ).Of note, outcomes in non-smokers for guided de-escalation vs. control group patients were mainly driven by a reduction in bleeding events (BARC ≥ grade 2) (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03,p=0.066).A Cox proportional hazards model revealed no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (p value for interaction=0.23). Conclusion:Guided de-escalation of DAPT appears to be equally safe and effective in smokers and non-smokers.Regardless of smoking status and especially for those patients deemed unsuitable for 1 year potent platelet inhibition this DAPT strategy may be used as an alternative antiplatelet treatment regimen.

OBJECTIVES:To investigate the impact of stent deformity induced by final kissing balloon technique (KBT) for coronary bifurcation lesions on in-stent restenosis (ISR).BACKGROUND:In experimental models, the detrimental effects of KBT have been clearly demonstrated, but few data exists regarding the impact of proximal stent deformity induced by KBT on clinical outcomes.METHODS:We examined 370 coronary lesions where intravascular ultrasound (IVUS)-guided second-generation drug-eluting stent (DES) implantation for coronary bifurcation lesions was performed. Based on IVUS analysis, the stent symmetry index (minimum/maximum stent diameter) and stent overstretch index (the mean of stent diameter/the mean of reference diameter) were calculated in the proximal main vessel.RESULTS:The stent symmetry index was significantly lower (0.75 ± 0.07 vs 0.88 ± 0.06, P < 0.0001) and the stent overstretch index was significantly higher (1.04 ± 0.08 vs 1.01 ± 0.06, P = 0.0007) in lesions with KBT (n = 174) compared to those without KBT (n = 196). The number of two-stent technique in lesions with KBT was 31 (18%). In multivariate analysis, the degree of stent deformity indices was not associated with ISR in lesions with KBT; however, two-stent technique use was the only independent predictor of ISR at 8 months (hazard ratio: 3.96, 95% confidence interval: 1.25-12.5, P = 0.01).CONCLUSIONS:Second-generation DES deformity induced by KBT was not associated with mid-term ISR.

Introduction: Coexistence of peripheral artery disease (PAD) in patients with acute coronary syndrome (ACS) associates higher incidence of bleeding complication and adverse events after PCI. Although the ankle-brachial index (ABI) is used in a simple, non-invasive diagnosis of PAD, few data exist regarding bleeding risk score which contains ABI in patients with undergoing PCI. Hypothesis: The combination of ABI and classical risk factors of bleeding complication would improve the predictive ability of outcome. Methods: Consecutive 843 patients (652 men; mean age, 68±12) with ACS who underwent PCI and ABI examination were analyzed. The presence of PAD was defined as ABI <0.9. The primary endpoint was 30-day bleeding which was defined according to Bleeding Academic Research Consortium classification grade ≥3. Additionally, we analyzed the major adverse cardiovascular event (MACE) as secondary endpoint which was defined as all-cause death, myocardial infarction, and stroke. Results: There were 140 (16.7%) pa...

Although statin therapy is beneficial in the setting of acute coronary syndrome (ACS), a substantial proportion of patients with ACS still do not receive the guideline-recommended lipid management in contemporary practice. We hypothesize that the low-density lipoprotein cholesterol (LDL-C) level at the time of admission might affect patient management and the subsequent outcome. Nine-hundred and forty-two consecutive patients with ACS who underwent percutaneous coronary intervention were analyzed retrospectively. The study patients were first divided into two groups based on the LDL-C level on admission: group A (n = 267), with LDL-C < 100 mg/dL; and group B (n = 675), with LDL-C ≥ 100 mg/dL. Each group was then further divided into those who were prescribed statins or not at the time of discharge from the hospital. The primary endpoint was all-cause death. In addition, we analyzed the serial changes of LDL-C within 1 year. Patients in group A were significantly older and more likely to have multiple comorbidities compared with group B. The proportion of patients who were prescribed statin at discharge was significantly smaller in group A compared with group B (57.7 vs. 77.3%, p < 0.001). During the median 4-year follow-up, there were 122 incidents of all-cause death. Multivariate Cox proportional hazard analysis revealed that LDL-C < 100 mg/dL on admission [hazard ratio (HR), 1.61; 95% confidence interval (CI), 1.09–2.39; p < 0.05] and prescription of statins at discharge (HR, 0.52; 95% CI, 0.36–0.76; p < 0.001) were associated significantly with all-cause death. Under these conditions, increasing LDL-C levels were documented during follow-up in those patients in group A when no statins were prescribed at discharge (79 ± 15–96 ± 29 mg/dL, p < 0.001), whereas these remained unchanged when statins were prescribed at discharge (79 ± 15–77 ± 22 mg/dL, p = 0.30). These results demonstrate that decreased LDL-C on admission in ACS led to less prescription for statins, which could result in increased death, probably due to underestimation of the baseline LDL-C.

Background: A number of previous studies have shown that myocardial viability can be assessed by positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG). However, there has been no multicenter study that verified the ability of this modality for diagnosing myocardial viability in Japan. We therefore conducted a prospective one arm’s unrandomized multicenter clinical trial in order to confirm the diagnostic ability of 18F-FDG for myocardial viability. Methods: This study included patients with heart failure and impaired left ventricular function where conventional myocardial perfusion scintigraphy was not contributive for the diagnosis of myocardial viability,and assessed the diagnostic ability of 18F-FDG for myocardial viability in these patients. The diagnostic ability was determined on the basis of post-coronary vascularization improvement in myocardial wall motion in a myocardial segment with 18F-FDG uptake (i.e., positive predictive value). We also assessed the safety of 18F-FDG.Results: Out of 49 patients who received 18F-FDG administration, 30 were included in the efficacy analysis set (mean age 64.4±14.6 years; 27 men and 3 women; mean follow-up period 228.6±74.5 days). The positive predictive value of 18F-FDG (95% two-sided confidence interval) in the 30 patients of the efficacy-analysis set was 63.9% (54.6-72.5%). Moreover, the proportion of patients with improved wall motion, on a per-patient basis, was 86.7% (26 of 30 cases). As for the safety, no serious adverse events occurred and the agent was well-tolerated.Conclusions: The identification of myocardial viability by 18F-FDG will be widely beneficial in predicting improvement in myocardial wall motion after coronary revascularization. No serious safety concerns associated with the use of 18F-FDG were observed.

Background: Final kissing balloon technique (KBT) for coronary bifurcation lesions induces proximal stent deformation. The aim of this study was to investigate the impact of second-generation drug-eluting stent deformation evaluating by intravascular ultrasound imaging on clinical outcomes. Methods: From February 2010 to April 2015, 377 consecutive bifurcation lesions treated with second-generation drug-eluting stents were divided into two groups according to KBT, KBT group (n = 176) and no-KBT group (n = 201). Based on intravascular ultrasound analysis, the stent symmetry index (minimum / maximum stent diameter) and the stent overstretch index (the mean of minimum and maximum stent diameter / the mean of minimum and maximum reference diameter) were calculated. Results: ACC/AHA type B2/C lesion was significantly greater in the KBT group compared with the no-KBT group (84% vs. 68%; p = 0.0004). The stent symmetry index was significantly lower (0.75 ± 0.07 vs. 0.87 ± 0.06; p Conclusion: Stent deformation induced by KBT for complex bifurcation lesions was not associated with adverse mid-term outcomes.

Although Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score based on angiographic scoring system was developed in patients with previous coronary artery bypass grafting (CABG), few data exist regarding its prognostic utility in patients undergoing percutaneous coronary intervention (PCI). We examined 272 patients with previous CABG (217 men; mean age, 70.4 ± 9.7 years) undergoing PCI. Severity of the coronary anatomy was evaluated using CABG-SYNTAX score. The primary end point of this study was cardiovascular death. The baseline CABG-SYNTAX score ranged from 2 to 53.5, with an average of 26.0 ± 10.2. In the index procedures, PCI for the native coronary accounted for nearly all patients (88%). During follow-up (median 4.1 years), 40 cardiovascular deaths had occurred. In multivariate analysis, age >75 years (hazard ratio [HR] 2.82, 95% CI 1.45 to 5.52), left ventricular ejection fraction <40% (HR 2.99, 95% CI 1.39 to 6.07), end-stage renal disease (HR 2.90, 95% CI 1.15 to 6.75), peripheral artery disease (HR 2.20, 95% CI 1.10 to 4.64), and CABG-SYNTAX score >25 (HR 2.37, 95% CI 1.19 to 5.05) were independent predictors of cardiovascular death. After creating a composite risk score in consideration of identified predictors, the freedom from cardiovascular death at 5 years was 98%, 86%, and 58% in the low (0 to 1), medium (2), and high (3 to 5) scores, respectively (p <0.001). The area under the receiver-operating characteristic curve for cardiovascular death for the CABG-SYNTAX and composite risk scores were 0.66 and 0.77, respectively (p <0.05). In conclusion, the combination of angiographic and clinical characteristics is useful for risk stratification in patients with previous CABG undergoing PCI.

We report on measurements of neutrino oscillation using data from the T2K long-baseline neutrino experiment collected between 2010 and 2013. In an analysis of muon neutrino disappearance alone, we find the following estimates and 68% confidence intervals for the two possible mass hierarchies: Normal Hierarchy: $\sin^2\theta_{23}=0.514^{+0.055}_{-0.056}$ and $\Delta m^2_{32}=(2.51\pm0.10)\times 10^{-3}$ eV$^2$/c$^4$ Inverted Hierarchy: $\sin^2\theta_{23}=0.511\pm0.055$ and $\Delta m^2_{13}=(2.48\pm0.10)\times 10^{-3}$ eV$^2$/c$^4$ The analysis accounts for multi-nucleon mechanisms in neutrino interactions which were found to introduce negligible bias. We describe our first analyses that combine measurements of muon neutrino disappearance and electron neutrino appearance to estimate four oscillation parameters and the mass hierarchy. Frequentist and Bayesian intervals are presented for combinations of these parameters, with and without including recent reactor measurements. At 90% confidence level and including reactor measurements, we exclude the region: $\delta_{CP}=[0.15,0.83]\pi$ for normal hierarchy and $\delta_{CP}=[-0.08,1.09]\pi$ for inverted hierarchy. The T2K and reactor data weakly favor the normal hierarchy with a Bayes Factor of 2.2. The most probable values and 68% 1D credible intervals for the other oscillation parameters, when reactor data are included, are: $\sin^2\theta_{23}=0.528^{+0.055}_{-0.038}$ and $|\Delta m^2_{32}|=(2.51\pm0.11)\times 10^{-3}$ eV$^2$/c$^4$.

A 78-year-old man with unstable angina showed 90 % stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitroprusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Importantly, there occurred slow flow again after balloon angioplasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neoatherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.

A 78-year-old man with unstable angina showed 90 % stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitro- prusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Impor- tantly, there occurred slow flow again after balloon angio- plasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neo- atherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.