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Background The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions. Methods GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years. Results Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment. Conclusions After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. AstraZeneca; Biosensors International Group; Medicines company

Background Angiography-derived physiological assessment of coronary lesions has emerged as an alternative to wire based assessment aiming at less-invasiveness and shorter procedural time as well as cost effectiveness in physiology-guided decision making. However, current available image-derived physiology software have limitations including the requirement of multiple projections and are time consuming.Methods/Design The ReVEAL iFR (Radiographic imaging Validation and EvALuation for Angio-iFR) trial is a multicenter, multicontinental, validation study which aims to validate the diagnostic accuracy of the Angio-iFR medical software device (Philips, San Diego, US) in patients undergoing angiography for Chronic Coronary Syndrome (CCS). The Angio-iFR will enable operators to predict both the iFR and FFR value within a few seconds from a single projection of cine angiography by using a lumped parameter fluid dynamics model. Approximately 440 patients with at least one de-novo 40% to 90% stenosis by visual angiographic assessment will be enrolled in the study. The primary endpoint is the sensitivity and specificity of the iFR and FFR for a given lesion compared to the corresponding invasive measures. The enrollment started in August 2019, and was completed in March 2021.Summary The Angio-iFR system has the potential of simplifying physiological evaluation of coronary stenosis compared with available systems, providing estimates of both FFR and iFR. The ReVEAL iFR study will investigate the predictive performance of the novel Angio-iFR software in CCS patients. Ultimately, based on its unique characteristics, the Angio-iFR system may contribute to improve adoption of functional coronary assessment and the workflow in the catheter laboratory.

Aim: Arterial stiffness results in elevated left ventricular filling pressure and can promote atrial remodeling due to chronic pressure overload. However, the impact of arterial stiffness on the process of atrial remodeling in association with atrial fibrillation (AF) has not been fully evaluated. Methods: We enrolled 237 consecutive patients diagnosed with AF who had undergone ablation; data from 213 patients were analyzed. Cardio-ankle vascular index (CAVI) was used as a marker of arterial stiffness. The left atrial (LA) and right atrial (RA) volumes were determined by computed tomography imaging; atrial conduction and voltage amplitude were evaluated using a three-dimensional electromapping system used to guide the ablation procedure. Result: In univariate analysis, CAVI significantly correlated with atrial structural and electrical remodeling (LA volume index, r =0.297, P =0.001; RA volume index, r =0.252, P =0.004; LA conduction velocity, r =0.254, P = 0.003; LA mean voltage, r =−0.343, P =0.001, RA mean voltage; r =−0.245, P =0.015). Multivariate regression analysis revealed that CAVI and plasma levels of N-terminal B-type natriuretic peptide were independent determinants of LA and RA remodeling, respectively. On the other hand, age and LA conduction velocity were independent variables with respect to CAVI. Age-adjusted CAVI was highest in long-standing persistent AF when compared with measures of persistent or paroxysmal AF. Conclusion: CAVI was closely associated with biatrial remodeling in patients diagnosed with AF. These results suggest that arterial stiffness may play a significant role with respect to disease progression.

Objectives: We investigated the impact of total stent length (TSL) and average nominal stent diameter (ASD) on 10-year mortality after percutaneous coronary intervention (PCI) in the SYNTAXES trial. Background: TSL and ASD in patients treated with PCI are associated with major adverse cardiovascular events. However, the treatment effect of PCI with extensive and/or small stenting as compared with coronary artery bypass grafting (CABG) for complex coronary artery disease has not been fully evaluated. Methods: Impacts on mortality of extensive stenting defined as TSL >100 mm and small stenting as ASD

Acquired idiopathic generalized anhidrosis (AIGA) causes heat intolerance which can be life-threatening but is often overlooked1 . Here we report a patient who developed AIGA possibly caused by immune-related adverse event (irAE) of pembrolizumab. Our case was a 73-year-old Japanese woman whose medical history included surgery for colorectal adenocarcinoma three years ago, and pulmonary adenocarcinoma which had been treated with pembrolizumab 10 months ago.

Aims The objective of the study is to assess the efficacy and safety of the novel Magic Touch sirolimus coated-balloon (SCB) when compared to the SeQuent Please Neo paclitaxel coated balloon (PCB) for the treatment of de-novo small vessel coronary artery diseases (SVD). Study design The TRANSFORM I study is a randomized, multicenter, non-inferiority trial with the intent to enroll a total of 114 patients with a de-novo SVD (≤2.5 mm). Vessel size will be pre-screened by on-line QCA. After successful pre-dilatation without major coronary dissections (type C-F) nor Thrombolysis In Myocardial Infarction trial [TIMI] grade flow ≤2, patients will be enrolled in a 1:1 randomization to receive treatment with either the novel SCB balloon or the comparative PCB balloon. The balloon sizing will be selected according to the lumen-based approach derived from optical coherence tomography (OCT). The primary endpoint is 6-month mean net lumen diameter gain (6-month minimum lumen diameter [MLD] minus baseline MLD) assessed by quantitative coronary analysis (QCA) with non-inferiority margin of 0.3 mm in per-protocol analysis. The clinical follow-up will be conducted up to 1 year. The enrollment started in September 2020 and will complete in April 2021. Conclusions The TRANSFORM I trial will assess the efficacy of novel SCB in terms of non-inferiority to conventional PCB with a novel OCT measurement approach in patients with a de-novo SVD. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT03913832 .

Aims: The feasibility of offline optical coherence tomography (OCT) guidance in bifurcation (with either two-dimensional or three-dimensional images) and its potential benefits have been demonstrated in retrospective studies; however, these have not yet been investigated prospectively. The aim of this trial is to determine the superiority of online three-dimensional optical frequency domain imaging (3D-OFDI)- guided stenting to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition (ISA) at the bifurcation segment. Methods and results: The OPTIMUM trial is a randomised, superiority, multicentre clinical trial. The primary endpoint of this trial is the post-procedural percentage of malapposed struts assessed by OFDI in the main branch bifurcation region after final kissing balloon dilatation (FKBD). A total of 106 patients will be randomly allocated to either 3D-OFDI guidance or angiography guidance PCI. Bifurcation lesions will be treated with a provisional single-stent strategy using the Ultimaster sirolimus-eluting stent. Patients randomised to the 3D-OFDI guidance arm will undergo OFDI assessment in the main branch (MV) after rewiring into the jailed side branch following stent implantation, while in the angiography guidance arm re-crossing of a wire into the side branch will be performed using conventional fluoroscopic/angiographic guidance. In patients in the 3D-OFDI guidance arm, if the position of the wire is not located in the optimal cell, further attempts to redirect the wire to the optimal cell will be performed, with subsequent OFDI acquisitions to confirm the re-crossing position. The proximal optimisation technique and FKBD are mandatory in this trial. The study will provide a 90% power to show superiority of 3D-OFDI guidance PCI compared with angiography-guided PCI. Conclusions: The OPTIMUM trial will be the first prospective, randomised trial to evaluate the efficacy and safety of online 3D-OFDI-guided PCI in bifurcation lesions. ClinicalTrials.gov Identifier: NCT02972489.

Intracoronary physiology is routinely used in setting the indication for percutaneous coronary intervention (PCI) but seldom in assessing procedural results. This attitude is increasingly challenged by accumulated evidence demonstrating the value of post-PCI functional assessment in predicting long-term patient outcomes. Besides fractional flow reserve, a number of new indexes recently incorporated to clinical practice, including nonhyperemic pressure and functional angiographic indexes, provide new opportunities for the physiological assessment of PCI results. Largely, the benefit of these tools is derived from longitudinal analysis of the treated vessel, which allows precise identification of the vessel segment accounting for a suboptimal functional result and enabling operators to perform accurate PCI optimization. In this document the authors review available evidence supporting why physiological assessment should be extended to immediate post-PCI with the aim of improving patient outcomes. A step-by-step guide on how available physiological tools can be used for such purpose is provided.

Aims Cardiohepatic interactions have been a focus of attention in heart failure (HF). The model for end‐stage liver disease excluding international normalized ratio (MELD‐XI) score has been shown to be useful for predicting poor outcomes in patients with acute decompensated HF (ADHF). Furthermore, the fibrosis‐4 (FIB‐4) index, a simple marker to assess liver fibrosis, predicts adverse prognoses in patients with HF as well. However, there is little information available on the prognostic significance of the combination of the MELD‐XI score and FIB‐4 index in patients with ADHF and its association with left ventricular ejection fraction (LVEF) subgroup. Methods and results We prospectively studied 466 consecutive patients who were admitted for ADHF [HF with reduced LVEF (LVEF

Supplemental Digital Content is available in the text., Background: Clinical implications of online 3-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting for bifurcation lesions have not been investigated in the randomized controlled trials. The purpose of this study was to determine whether online 3D-OFDI-guided stenting is superior to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition at the bifurcation segment. Methods: The OPTIMUM trial (Online 3-Dimensional Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent) was a randomized, multicenter clinical trial. Eligible patients had an angiographically significant stenosis in the bifurcation lesion treated with a provisional single stent strategy using the Ultimaster sirolimus eluting stent. Patients were randomly allocated to either online 3D-OFDI-guided or angiography-guided PCI. Patients randomized to 3D-OFDI guidance underwent online 3D-OFDI assessment after rewiring into the jailed side branch after stenting and proximal optimization technique, while in the angiography guidance arm, rewiring was performed using conventional fluoroscopic/angiographic guidance. The primary end point of this trial was the postprocedural average percentage of malapposed struts per lesion assessed by OFDI in the confluence zone of the main and side branches. Results: Between June 8, 2017 and September 26, 2018, 110 patients with 111 bifurcation lesions were randomized at 4 Japanese centers. Of these, 56 patients with 57 lesions were treated with 3D-OFDI-guided PCI, whereas 54 patients with 54 lesions were treated with angiography-guided PCI. In the 3D-OFDI guidance arm, the feasibility of online 3D-OFDI was 98.2%. The average percentage of incomplete stent apposition per lesion at bifurcation was lower in the 3D-OFDI guidance arm than that in the angiography guidance arm (19.5±15.8% versus 27.5±14.2%, P=0.008). The superiority of the 3D-OFDI guidance arm was also confirmed in the strut level analysis (odds ratio: 0.54 [95% CI, 0.36–0.81]; P=0.003). Conclusions: Online 3D-OFDI-guided bifurcation PCI was superior to angiography-guided bifurcation PCI in terms of acute incomplete stent apposition at bifurcation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02972489.

Objectives: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). Background: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. Methods: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. Results: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p

Aims The aim of this study is to demonstrate the non-inferiority of the BiOSS LIM C sirolimus-eluting cobalt-chromium bifurcation dedicated stent against the XIENCE stent regarding the patient-oriented composite endpoint (POCE) at 12 months among patients with left main coronary artery disease (LMCA). Methods and results The POLBOS LM study is a single-arm, prospective, multicentre study enrolling 260 patients (SYNTAX score ≤32) with a pre-specified performance goal based on the results of the EXCEL trial with contemporary percutaneous coronary intervention (PCI) for LMCA disease. Patient enrolment will comply with objective inclusion criteria of diameter stenosis ≥50% in the LMCA based on off-line quantitative coronary angiography (QCA) analysed by an independent core laboratory using dedicated bifurcation QCA software. The BiOSS LIM C is used for the treatment of LMCA disease with the same specific technical classification as for the BiOSS LIM (modified MADS classification) and the stent implantation is optimised by using pre-specified intravascular ultrasound criteria. The primary endpoint is POCE (a composite of all-cause death, stroke, any myocardial infarction, and any revascularisation) at 12 months. Conclusions The POLBOS LM study will indicate the efficacy of the BiOSS LIM C stent with contemporary PCI for distal left main bifurcation lesions in comparison with the XIENCE stent from the recent EXCEL trial, as a performance index.

Objectives The aim of this study was to evaluate the hypothesis that prasugrel monotherapy following successful everolimus-eluting stent implantation is feasible and safe in patients with stable coronary artery disease (CAD). Background Recent studies have suggested that short dual-antiplatelet therapy strategies may provide an adequate balance between ischemic and bleeding risks. However, the complete omission of aspirin immediately after percutaneous coronary intervention (PCI) has not been tested so far. Methods The study was a multicenter, single-arm, open-label trial with a stopping rule based on the occurrence of definite stent thrombosis (if >3, trial enrollment would be terminated). Patients undergoing successful everolimus-eluting stent implantation for stable CAD with SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores Results From February 22, 2018, to May 7, 2019, 201 patients were enrolled. All patients underwent PCI for stable CAD. Overall, 98.5% of patients were adherent to prasugrel at 3-month follow-up. The primary ischemic and bleeding endpoints occurred in 1 patient (0.5%). No stent thrombosis events occurred. Conclusions Aspirin-free prasugrel monotherapy following successful everolimus-eluting stent implantation demonstrated feasibility and safety without any stent thrombosis in selected low-risk patients with stable CAD. These findings may help underpin larger randomized controlled studies to evaluate the aspirin-free strategy compared with traditional dual-antiplatelet therapy following PCI. (Acetyl Salicylic Elimination Trial: The ASET Pilot Study [ASET]; NCT03469856)

Introduction: The technology of bioresorbable scaffold (BRS) spread out after the success of the first-in-man trials of the Absorb. However, the randomized trials demonstrated that major adverse cardiac events and scaffold thrombosis rates of the first-generation Absorb were higher than those of the metallic everolimus-eluting stent. To overcome the shortcoming of the firstly commercialized Absorb, novel technologies have been developed. Areas covered: In this review, we overviewed the field of BRS in the treatment of coronary, peripheral artery and gastrointestinal fields. To date, 10 BRS devices developed by 6 manufacturers have acquired the CE mark in coronary artery disease. Currently 8 BRS are in clinical trial phase, whereas 7 BRS are in preclinical assessment phase. Most new-generation devices have a strut thickness of less than 100 μm. However, late favorable outcome might be achieved not only by device refinement but also by a proper technique of implantation using intra vascular imaging guidance, as well as with a careful patient and lesion selection. Expert opinion: New-generation BRS will be soon tested in the clinical arena to demonstrate improved acute and long-term of safety and efficacy.

Aims To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence. Methods and results This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21–3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58–1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm. Conclusion In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected. Clinical trial registration unique identifier NCT01813435.

It has been hypothesized that dedicated optimized Absorb BVS implantation techniques might mitigate the risk of adverse events such as target vessel failure and device thrombosis. In this explorative AIDA trial QCA substudy, we sought to investigate the influence of implantation techniques on lesion-oriented outcomes in both the Absorb BVS and Xience EES arm at complete 3-year follow-up. The current analysis includes 2152 study lesions treated with at least one study device, of which the baseline angiogram was suited for offline QCA analysis, including Dmax analysis. The lesion-oriented composite outcome (LOCE) of this analysis was a composite of definite device thrombosis, target lesion revascularization and target-vessel myocardial infarction. In Absorb BVS, the Lesion-oriented composite endpoint (LOCE) occurred numerically less in correctly QCA sized vessels when compared to incorrectly sized vessels 8.5% (58/696) versus 11.1% (39/358), p = 0.151. In Xience EES, LOCE had occurred more frequently in incorrectly sized devices according to device diameter/RVD matching; 2.2% (4/187) in correctly sized devices versus 7.1% (63/911) in incorrectly sized devices (p = 0.014). In this AIDA trial QCA substudy, rates of LOCE were significantly lower in Xience EES treated lesions in which devices were correctly sized according to the definitions of device diameter/RVD matching.

We performed gross and histological examinations of the livers of sika deer (Cervus nippon yesoensis) in Hokkaido, Japan. Out of 1,381 deer slaughtered for venison production, thickening and dilation of the large intrahepatic bile ducts and Fasciola flukes in the duct lumens were detected in 621 deer (45.0%). Furthermore, 107 non-bile lesions (75 intrahepatic and 32 capsular lesions) were detected during gross examinations. Histologically, the bile duct lesions included chronic proliferative cholangitis, papillary hyperplasia, goblet cell and pyloric gland metaplasia, and periductal fibrosis. Many of the intrahepatic non-bile duct lesions (53/75, 71%) were considered to be Fasciola fluke migration-associated lesions, including two lesion types: necrosis, hemorrhage, and eosinophilic granuloma formation (29 lesions), and lymphoid tissue formation (24 lesions). Lymphoid tissue formation was considered to result from the persistent immune responses against dead Fasciola flukes. An epidermoid liver cyst was found incidentally, which has not been reported in the veterinary literature. In summary, this study demonstrated the predominance of fascioliasis-associated lesions in sika deer livers. The gross and histological lesions caused by Fasciola flukes in sika deer were similar to fascioliasis in other animals. Moreover, we described lymphoid tissue formation as a fascioliasis-associated lesion for the first time. The fact that bile duct lesions (45.0%) had a markedly higher prevalence than fascioliasis-associated parenchymal lesions (53/1,381, 3.8%) indicated that sika deer are a permissive host for fascioliasis. Our results provide information that will aid pathological examinations of sika deer.

Various studies have revealed that psychological stress enhances pruritus.1,2 The COVID-19 pandemic have increased psychological stress. People may feel additional psychological stress in at-risk circumstances for the spread of COVID-19 infection. However, it is unknown whether at-risk circumstances for COVID-19, such as confirmed infection in acquaintances, are associated with the risk of pruritus. Thus, we investigated the association between at-risk circumstances and pruritus in the general population via cross-sectional and longitudinal analyses.

A white nodule was detected in the liver of a wild female sika deer. The nodule was histologically diagnosed as squamous cell carcinoma (SCC), and it transitioned into a hyperplastic and chronically inflamed intrahepatic bile duct showing Fasciola infection. Therefore, the tumor was demonstrated to have originated from the biliary epithelium of the intrahepatic bile duct. Hyperplastic and chronic inflammatory changes of the biliary epithelium might have contributed the carcinogenesis of the present case, as proposed in human primary intrahepatic SCC cases. To the best of our knowledge, this is the first reported case of primary intrahepatic SCC in an animal.

Aims The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days. Methods and results In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99–1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44–1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77–3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients. Conclusion In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion.

OBJECTIVES The aim of this study was to investigate the impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) on clinical outcomes in patients with de novo 3-vessel disease (3VD) treated with contemporary PCI.BACKGROUND The clinical impact of post-PCI QFR in patients treated with state-of-the-art PCI for de novo 3VD is undetermined.METHODS All vessels treated in the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) II trial were retrospectively screened and analyzed for post-PCI QFR. The primary endpoint of this substudy was vessel-oriented composite endpoint (VOCE) at 2 years, defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The receiver-operating characteristic curve was used to calculate the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE. All the analyzable vessels were stratified on the basis of the optimal cutoff value.RESULTS A total of 968 vessels treated with PCI were screened. Post-PCIQFR was analyzable in 771 (79.6%) vessels. A total of 52 (6.7%) VOCEs occurredat 2 years. The mean value of post-PCIQFR was 0.91 +/- 0.07. The diagnostic performance of post-PCI QFR to predict 2-year VOCE was moderate (area under the curve: 0.702; 95% confidence interval: 0.633 to 0.772), with the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE 0.91 (sensitivity 0.652, specificity 0.635). The incidence of 2-year VOCE in the vessels with post-PCIQFR= 0.91 (n = 487) (12.0% vs. 3.7%; hazard ratio: 3.37; 95% confidence interval: 1.91 to 5.97; p < 0.001).CONCLUSIONS A higher post-PCI QFR value is associated with improved vessel-related clinical outcomes in state-of the art PCI practice for de novo 3VD. Achieving a post-PCI QFR value >= 0.91 in all treated vessels should be a target when treating de novo 3VD. These findings require confirmation in future prospective trials. (C) 2019 by the American College of Cardiology Foundation.

Aims: The aim of this study is to compare the SUPRAFLEX sirolimus-eluting stent (SES) with the XIENCE everolimus-eluting stent (EES) with respect to target lesion failure (TLF) at 12 months in a noninferiority trial in a “real-world” patient population. Methods and results: This is a prospective, randomised, 1:1 balanced, controlled, single-blind, multicentre study comparing clinical outcomes at 12 months between SUPRAFLEX and XIENCE in an “allcomers” patient population, comprising a total of 1,430 enrolled subjects with symptomatic coronary artery disease who qualify for percutaneous coronary interventions at 23 centres in Europe. The primary endpoint is a non-inferiority comparison of the device-oriented composite endpoint target lesion failure (cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularisation) of the SUPRAFLEX group to the XIENCE group at 12 months post procedure. Secondary endpoints include the patient-oriented composite endpoint, target vessel failure, mortality, myocardial infarction, revascularisation and stent thrombosis rates (ARC classification). Conclusions: The TALENT trial aims to assess the safety and effectiveness of the thin-strut SUPRAFLEX compared to the current standard of care (XIENCE EES) in patients with atherosclerotic lesions. This will provide valuable information on the impact of this thin-strut device in an all-comers population.

The Absorb bioresorbable scaffold (BRS), the most studied device among all BRS, suffered a major setback following the negative results of the ABSORB trials. However, approximately 34 BRSs from 22 companies are currently under development. The potential device-specific factors related to the increased event rate in Absorb were: 1) weak mechanical properties, 2) larger strut thickness (less embedment and larger protrusion) and width (larger footprint) predisposing to underexpansion/protrusion of struts, eventually resulting in increased thrombogenicity, and 3) longer bioresorption time combined with failure of encapsulation of struts before the dismantling process ensues. Given the diversity of bioresorbable materials (even amongst PLLA), and the different mechanical properties and bioresorption profiles of each new BRS, one could expect considerable difference in early and late clinical outcomes. As a matter of fact, data from first-in-man (FIM) and pivotal trials have demonstrated variable clinical results. Indeed, early clinical evidence from FIM trials does not support a class effect. However, the absence of a comparator precludes us from drawing definitive conclusions. Further clinical evidence should confirm the absence (or presence) of a class effect.

OBJECTIVES Invasive coronary angiography has been the preferred diagnostic method to guide the decision-making process between coronary artery bypass grafting (CABG) and percutaneous coronary intervention and plan a surgical revascularization procedure. Guidelines recommend a heart team approach and assessment of coronary artery disease (CAD) complexity, objectively quantified by the anatomical SYNTAX score. Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) are emerging technologies in the diagnosis of stable CAD. In this study, data from patients with left main or 3-vessel CAD who underwent CABG were evaluated to assess the feasibility of developing a surgical plan based on CCTA integrated with FFRCT. The primary objective was to assess the theoretical feasibility of surgical decision-making and treatment planning based only on non-invasive imaging. METHODS This study represents a survey of surgeons involved in the SYNTAX III Revolution trial. In this trial, heart teams were randomized to make treatment decisions using CTA. CCTAs and FFRCT results of 20 patients were presented to 5 cardiac surgeons. RESULTS Surgical treatment decision-making based on CCTA with FFRCT was considered feasible by a panel of surgeons in 84% of the cases with an excellent agreement on the number of anastomoses to be made in each patient (intraclass correlation coefficient 0.77, 95% confidence interval 0.35–0.96). CONCLUSIONS Using non-invasive imaging only in patients with left main or 3-vessel CAD, an excellent agreement on treatment planning and the number of anastomoses was found among cardiac surgeons. Thus, CABG planning based on non-invasive imaging appears feasible. Further investigation is warranted to determine the safety and feasibility in clinical practice.

Background: Little is known about serial changes in lumen and device dimensions after bioresorbable scaffold implantation in a growing animal model. Methods and Results: ABSORB (n=14) or bare metal stents (ICROS amg [Abbott Vascular, Santa Clara, CA, USA], Winsen-Luhe, Germany; n=15) were implanted in the coronary arteries of domestic swine (a hybrid of Finnish-Norwegian Landrace swine) weighing 30–35kg. Angiography and optical coherence tomography (OCT) were performed immediately after implantation and repeated at 7 days, 1, 3, 6 and 12 months after the index procedure. One month after implantation, mean lumen area decreased relative to baseline in both groups (relative area change from baseline, −41.4±15.6% for ABSORB vs. −20.9±18.6% for ICROS) while mean device area decreased only in the ABSORB group (relative area change: −11.1±9.4% vs. +0.14±7.95%, respectively). At 12 months, mean lumen area increased relative to baseline in both groups (relative area change from baseline, +55.6±22.4% vs. +32.3±83.6%, respectively) in accordance with the swine growth weighing up to 260–300kg. Mean device area in the ICROS group remained stable whereas that in the ABSORB group began to increase between 3 and 6 months along with the vessel growth (relative area change: +107.8±25.7% vs. +0.14±7.95%). Conclusions: In the growing porcine model, ABSORB was associated with greater extent of recoil 1 month after implantation compared with ICROS but demonstrated substantial adaptability to vessel growth in late phase.

Introduction: Drug-eluting stents (DES) are still the standard of care in percutaneous coronary intervention (PCI) since the fall of bioresorbable scaffolds with respect to safety. The unbeatable advantage of a metallic stent when compared with a scaffold is a stronger mechanical property and more sustainable vascular support. Recent development of contemporary metallic stent has focused on the reduction of strut thickness. However, there will always be a trade-off between improvement in deliverability, flexibility, and radial strength. Areas covered: This review aims to discuss the designs of metallic stent platform and mechanical properties as well as mechanical performance of contemporary DES from bench studies and clinical trials. Expert opinion: Mechanical properties of stents affect short- and long-term clinical outcomes. Ultrathin-strut DES have become popular and clinical trials have shown impressive results. Thinner struts may improve device flexibility and deliverability but the radial strength and longitudinal integrity might have been compromised as well. Ultrathin-strut cobalt chromium or platinum chromium DES will become standard of care in PCI practice in the near future. Information on the stent design, stent material and mechanical properties of the stent are essential for a rational selection of the appropriate stent in selected lesions and patients.

Objectives The aims of the present study were to investigate the applicability of quantitative flow ratio (QFR) in patients with 3-vessel disease and to demonstrate the impact of functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score derived from QFR (fSSQFR) on clinical outcomes. Background The applicability of QFR in patients with 3-vessel disease and the feasibility of fSSQFR have not yet been investigated. Methods All lesions interrogated using instantaneous wave-free ratio and/or fractional flow reserve in the SYNTAX II trial were retrospectively screened and analyzed for QFR. The diagnostic performance of QFR was investigated using hybrid wire-derived pressure assessment (instantaneous wave-free ratio and fractional flow reserve), used in the trial as a reference. Patients with analyzable QFR in 3 vessels were stratified according to fSSQFR to evaluate its clinical prognostic value on the basis of 2-year patient-oriented composite endpoint. Results QFRs were analyzable in 71.0% of lesions (836 lesions). The diagnostic performance of QFR to predict binary wire-based ischemia was substantial (area under the curve 0.81, accuracy 73.8%), with a positive predictive value of 85.9%. Independent predictors of diagnostic discordance were lesions in side branches, involvement of bifurcation or trifurcation, and small vessel. According to the 2-year patient-oriented composite endpoint, fSSQFR reclassified 26.1% of the patients (36 of 138) in the high- to intermediate-risk group into the low-risk group appropriately (net reclassification improvement 0.32; p Conclusions QFR demonstrated substantial applicability in patients with 3-vessel disease. The fSSQFR has the potential to further refine prognostic risk estimation compared with the classic anatomic SYNTAX score.

Highlights • US-IMPT can potentially reduce the risk of genitourinary toxicities. • The urethral NTCP value in US-IMPT is significantly lower than in the clinical plan. • TCP for CTV did not differ significantly between the clinical and US-IMPT plans., Background and Purpose Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. Materials and Methods This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman–Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. Results The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p

To investigate the association between occupational direct radiation exposure to the hands and longitudinal melanonychia (LM) and hand eczema in spine surgeons. A web-based questionnaire survey of the Society for Minimally Invasive Spinal Treatment (MIST) in Japan was conducted. The proportion of LM and hand eczema in hands with high and low-radiation exposure was compared using Fisher’s exact test. The odds ratios (ORs) and their 95% confidence intervals (CIs) for the prevalence of LM and hand eczema in the high-radiation exposure hands were calculated using generalized estimating equations for logistic regression as control for the correlation of observations among the same individuals and possible confounders. Among 324 members of the society, responses were received from 229 members (70.7%). A total of 454 hands from 227 participants were analysed. The prevalence of LM and hand eczema was 43% and 29%, respectively. In a hand-by-hand comparison, more hands had LM in the high-radiation exposure group than the low-radiation exposure group (90 [40%] vs. 39 [17%], respectively, p

Surfactant-induced cumulative irritant contact dermatitis (ICD) is a common and clinically important skin disorder. CCL2 is known to mediate inflammation after tissue damage in various organs. Thus, we investigated whether and how CCL2 contributes to the development of murine cumulative ICD induced by a common surfactant, SDS. Wild-type mice treated topically with SDS for 6 consecutive days developed skin inflammation that recapitulated the features of human cumulative ICD, including barrier disruption, epidermal thickening, and neutrophil accumulation. CCL2 was upregulated in SDS-treated skin, and local CCL2 blockade attenuated SDS-induced ICD. SDS-induced ICD and neutrophil accumulation were also attenuated in mice deficient in CCR2, the receptor for CCL2. Neutrophil depletion alleviated SDS-induced ICD, suggesting that impaired neutrophil accumulation was responsible for the amelioration of ICD in CCR2-deficient mice. In RNA-sequencing analyses of SDS-treated skin, the expression levels of Il1b in Ccr2-deficient mice were highly downregulated compared with those in wild-type mice. Furthermore, the intradermal administration of IL-1β in the SDS-treated skin of CCR2-deficient mice restored the local accumulation of neutrophils and the development of ICD. Collectively, our results suggest that CCL2‒CCR2 signaling in the skin critically promotes the development of SDS-induced ICD by inducing IL-1β expression for neutrophil accumulation.

AIMS We aimed to update the logistic clinical SYNTAX score to predict 2��year all-cause mortality after contemporary percutaneous coronary intervention (PCI). METHODS AND RESULTS We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2��year all-cause mortality and included into the new model. The c-indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72-0.76), 0.75 (95% CI 0.73-0.77), and 0.78 (95% CI 0.76-0.80), respectively. The c-index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67-0.77) compared to the refitted original model (0.69; 95% CI 0.64-0.74). The models overestimated the observed 2��year all-cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population. CONCLUSIONS The new model of the logistic clinical SYNTAX score better predicts 2��year all-cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI.

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with followup completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87 [95% CI 0. 75-1. 01]; p=0.073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0.93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2.04% vs 2.12%; rate ratio 0.97 [95% CI 0. 78-1. 20]; p=0.77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Copright (C) 2018 Elsevier Ltd. All rights reserved. European Clinical Research Institute; Biosensors International; AstraZeneca; Medicines Company; Canada Research Chairs Programme

Background: The efficacy of antiplatelet therapies following percutaneous coronary intervention (PCI) may be affected by body mass index (BMI). Methods and results: This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. Conclusions: Overall, BMI did not influence the treatment effect seen with ticagrelor monotherapy; however, a beneficial effect of ticagrelor monotherapy was seen in ACS patients with BMI < 27 kg/m2. Trial registration: The trial has been registered with ClinicalTrials.gov, Number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].

Background: Time-to-first-event analysis considers only the first event irrespective of its severity. There are several methods to assess trial outcomes beyond time-to-first-event analysis, such as analyzing total events and ranking outcomes. In the GLOBAL LEADERS study, time-to-first-event analysis did not show superiority of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention to conventional 12-month DAPT followed by aspirin monotherapy in the reduction of the primary composite end point of all-cause mortality or new Q-wave myocardial infarction. This study sought to explore various analytical approaches in assessing total ischemic and bleeding events after percutaneous coronary intervention in the GLOBAL LEADERS study. Methods and Results: Total ischemic and bleeding events were defined as all-cause mortality, any stroke, any myocardial infarction, any revascularization, or Bleeding Academic Research Consortium grade 2 or 3 bleeding. We used various analytical approaches to analyze the benefit of ticagrelor monotherapy over conventional DAPT. For ischemic and bleeding events at 2 years after percutaneous coronary intervention, ticagrelor monotherapy demonstrated a 6% risk reduction, compared with conventional 12-month DAPT in time-to-first-event analysis (hazard ratio, 0.94 [95% CI, 0.88–1.01]; log-rank P =0.10). In win ratio analysis, win ratio was 1.05 (95% CI, 0.97–1.13; P =0.20). Negative binomial regression and Andersen-Gill analyses which include repeated events showed statistically significant advantage for ticagrelor monotherapy (rate ratio, 0.92 [95% CI, 0.85–0.99; P =0.020] and hazard ratio, 0.92 [95% CI, 0.85–0.99; P =0.028], respectively), although in weighted composite end point analysis, the hazard ratio was 0.93 (95% CI, 0.84–1.04; log-rank P =0.22). Conclusions: Statistical analyses considering repeated events or event severity showed that ticagrelor monotherapy consistently reduced ischemic and bleeding events by 5% to 8%, compared with conventional 1-year DAPT. Applying multiple statistical methods could emphasize the multiple facets of a trial and result in accurate and more appropriate analyses. Considering the recurrence of ischemic and bleeding events, ticagrelor monotherapy appeared to be beneficial after percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

Background: Radial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. Methods: Patients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. Results: In the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. Conclusions: Our findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.

Aims The purpose of the Multivessel TALENT trial is to compare clinical outcomes of the novel Supraflex Cruz stent with those of the SYNERGY stent in patients with three-vessel disease (3VD) undergoing state-of-the-art percutaneous coronary intervention (PCI). Methods and results In this prospective, randomised, 1:1 balanced, multicentre, open-label trial, 1,550 patients with de novo 3VD without left main disease will be assigned to the Supraflex Cruz or SYNERGY arm. The following treatment principles of "best practice" PCI will be applied: Heart Team consensus based on SYNTAX score II treatment recommendation, functional lesion evaluation by quantitative flow ratio (QFR), stent optimisation by intravascular imaging, optimal pharmacological treatment and prasugrel monotherapy. The primary endpoint is a non-inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any revascularisation, at 12 months post procedure. The powered secondary endpoint is a superiority comparison of the vessel-oriented composite endpoint (VOCE), defined as vessel-related cardiovascular death, vessel-related myocardial infarction, or clinically and physiologically indicated target vessel revascularisation, at 24 months. Conclusions The Multivessel TALENT trial will be evaluating a novel treatment strategy for complex coronary artery disease with state-of-the-art PCI based on angiography-derived QFR with novel ultra-thin Supraflex Cruz stents, compared with SYNERGY stents. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ct2/show/NCT04390672. Unique Identifier: NCT04390672 Visual summary. Flow chart of the Multivessel TALENT trial. 3VD: three-vessel disease; QFR: quantitative flow ratio; IVUS: intravascular ultrasound; OCT: optical coherence tomography; CTO: chronic total occlusion; OMT: optimal medical therapy; POCE: patient-oriented composite endpoint; VOCE: vessel-oriented composite endpoint.

Background Atrial fibrillation (AF) induces functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) during atrial remodeling. FMR and FTR are associated with AF prognosis, but the effects for AF recurrence after ablation have not been determined conclusively. Methods Two hundred thirty nine patients who underwent AF ablation were enrolled. Forty five patients were excluded. In total, 194 patients were analyzed. FMR and FTR were assessed by echocardiography. The left atrial volume index (LAVI) was evaluated by contrast-enhanced computed tomography. Results Significant FMR and moderate FTR were observed in 15 (7.7%) and in 25 (12.9%) patients, respectively. The severity of tricuspid regurgitation (TR) significant correlated with age, NT-proBNP, and LAVI. During a 13.4 month follow-up period of, 39 patients (20.1%) demonstrated AF recurrence. In the Cox proportional-hazards model, E/e’, FTR, and LAVI, were termed as predictor factors of AF recurrence (E/e’. hazard ratio [HR] = 1.117; P = 0.019, significant FTR. HR = 4.679; P = 0.041, LAVI. HR = 1.057; P = 0.003). Kaplan–Meier analysis showed that AF recurrence was more frequent in FTR compared with the nonsignificant FTR cases (log-rank, P = 0.001). Although survival analysis showed no difference with or without FMR, the presence of FMR and FTR was strongly associated with high-AF recurrence (log-rank, P = 0.004). Conclusions AF recurrence was associated with E/e’, LAVI, and extensive FTR. Specifically, the combination of FTR and FMR markedly worsens the AF prognosis.

Background Although polypharmacy is known to cause side effects due to drug-drug interactions, dermatological symptoms triggered by polypharmacy are not fully addressed. Objective To investigate whether polypharmacy is associated with the risk of pruritus METHOD: A cohort study was performed to examine cross-sectional and longitudinal relationships between polypharmacy and pruritus in a general population. Data were collected from the Norm Study conducted in 2016 and 2017, which is a nationwide survey based on a self-administered questionnaire with Japanese representative participants aged 16-84 years. Presence of polypharmacy which was defined as concurrent use of ≥5 prescribed drugs. Primary outcomes were the presence of severe pruritus at baseline for the cross-sectional analysis and the development of severe pruritus after one year for the longitudinal analysis. Multivariable modified Poisson regression analyses were performed to estimate risk ratios (RRs) and 95% confidence intervals (95%CIs) with adjustment for potential confounders (age, gender, smoking habits, drinking habits, depressive symptoms, moderate activities based on IPAQ score, and presence of 11 comorbid conditions including skin disease). Results The study included 3,126 participants (mean age, 48.7 years); nearly half (49.8%) were male. In all, 332 participants (10.3%) had polypharmacy in the cross-sectional analysis. Participants with polypharmacy were more likely to present with severe pruritus at baseline than those who were not using drugs (adjusted RR = 1.52 [95%CI 1.15-2.01, P = 0.003]). The longitudinal analysis (n = 1,803) was limited to those without severe pruritus at baseline; participants with polypharmacy at baseline were more likely to develop severe pruritus after a one-year follow-up period than those not using drugs (adjusted RR = 1.46 [95%CI 1.14-1.87, P = 0.002]). Conclusion Polypharmacy was associated with the presence of pruritus at baseline and may predict the future risk of developing pruritus.

Background and purpose Supraflex is a sirolimus-eluting stent with a biodegradable polymeric coating and 60um ultra-thin struts. In the TALENT study, we found the Supraflex stent was non-inferior to the Xience stent for a device-oriented composite endpoint (DOCE, defined as cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation) at 12 months in an all-comer population. Additionally, per-protocol analysis showed a significantly lower clinically indicated target lesion revascularisation (CI-TLR) in the Supraflex group than in the Xience group. We now present the 2-year follow-up results. Methods The TALENT study was a prospective, randomised, single-blind, multicentre study across 23 centres in Europe. Eligible participants underwent percutaneous coronary intervention in an all-comers fashion in vessels of 2.25–4.5 mm. Patients were randomized (1:1) to implantation of either Supraflex or Xience (NCT02870140). Results Between October 21, 2016 and July 3, 2017, 720 patients with 1046 lesions were randomly assigned to Supraflex, and 715 patients with 1030 lesions to Xience. At 24 months, DOCE had occurred in 49 patients (6.9%) in the Supraflex group and in 56 patients (7.9%) in the Xience group (absolute difference −1.0% [95% CI: −3.7 to 1.7], Plog-rank=0.491). Per-protocol analysis at 24 months showed CI-TLR occurred in 21 and 30 patients in the Supraflex and Xience, respectively (3.3% versus 4.5%, absolute difference −1.2%, [95% CI: −3.3 to 0.9], Plog-rank=0.267). Conclusion In an all-comer population, at 2-year follow-up, the use of Supraflex stent was at least as safe and efficacious as Xience stent. However, the significantly lower rate of CI-TLR shown in patients treated with Supraflex at 1-year was no longer retained in the 2-year results. Whether theoretical advantage of ultra-thin strut drug eluting stents Supraflex can translate into clinical benefit or not will be further elucidated through a total of 3 years of follow-up. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): SMT

Highlights • Post urination MRI is useful for urethra-sparing radiotherapy treatment planning. • This prospective clinical trial included 11 prostate cancer patients. • Post urination MRI is the identification method of prostatic urinary tract in non-invasive manner., The urethra position may shift due to the presence/absence of the catheter. Our proposed post-urination-magnetic resonance imaging (PU-MRI) technique is possible to identify the urethra without catheter. We aimed to verify the inter-operator difference in contouring the urethra by PU-MRI. The mean values of the evaluation indices of dice similarity coefficient, mean slice-wise Hausdorff distance, and center coordinates were 0.93, 0.17 mm, and 0.36 mm for computed tomography, and 0.75, 0.44 mm, and 1.00 mm for PU-MRI. Therefore, PU-MRI might be useful for identifying the prostatic urinary tract without using a urethral catheter. Clinical trial registration: Hokkaido University Hospital for Clinical Research (018-0221).

Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2). Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35–1.98, p adj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61–1.11, p = 0.192, p int = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71–1.71, p = 0.656, p int = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. Clinical trial registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 μm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10–20 μm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalities—IVUS and OCT—and discuss the expected potential of the novel hybrid IVUS–OCT catheter system in the clinical field.

Contains fulltext : 225405.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: The prognostic impact of pre-procedure heart rate (PHR) following percutaneous coronary intervention (PCI) has not yet been fully investigated. This post-hoc analysis sought to assess the impact of PHR on medium-term outcomes among patients having PCI, who were enrolled in the "all-comers" GLOBAL LEADERS trial. METHODS AND RESULTS: The primary endpoint (composite of all-cause death or new Q-wave myocardial infarction [MI]) and key secondary safety endpoint (bleeding according to Bleeding Academic Research Consortium [BARC] type 3 or 5) were assessed at 2 years. PHR was available in 15,855 patients, and when evaluated as a continuous variable (5 bpm increase) and following adjustment using multivariate Cox regression, it significantly correlated with the primary endpoint (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.09, p 67 bpm was associated with increased all-cause mortality (HR 1.38, 95%CI 1.13-1.69, p = 0.002) and more frequent new Q-wave MI (HR 1.41, 95%CI 1.02-1.93, p = 0.037). No significant association was found between PHR and BARC 3 or 5 bleeding (HR 1.04, 95% CI 0.99-1.09, p = 0.099). There was no interaction with the primary (p-inter = 0.236) or secondary endpoint (p-inter = 0.154) when high and low PHR was analyzed according to different antiplatelet strategies. CONCLUSIONS: Elevated PHR was an independent predictor of all-cause mortality at 2 years following PCI in the "all-comer" GLOBAL LEADERS trial. The prognostic value of increased PHR on outcomes was not affected by the different antiplatelet strategies in this trial.

Background: Numerous randomized clinical trials have demonstrated the superiority of thin-strut biodegradable polymer second-generation drug-eluting stent to the first-generation drug-eluting stent and the noninferiority to the thin-strut second-generation permanent polymer drug-eluting stent. Data on long-term clinical outcomes with a novel ultrathin drug-eluting stent, to date, are limited. Methods: The DESSOLVE III trial (Multicenter Randomized Study of the MiStent Sirolimus Eluting Absorbable Polymer Stent System for Revascularization of Coronary Arteries; n=1398) is a prospective, multicenter, single-blinded, all-comers, randomized controlled trial (NCT02385279), allocating in a 1:1 ratio to either ultrathin-strut biodegradable polymer MiStent sirolimus-eluting stent or to thin-strut permanent polymer Xience everolimus-eluting stent. The primary end point was device-oriented composite end point, defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. The secondary end point was patient-oriented composite end point, defined as the composite of all-cause mortality, any myocardial infarction, or any revascularization. Results: At 3 years, follow-up data were available in 1381 patients (98.8%). The primary end point of device-oriented composite end point occurred in 10.5% for MiStent sirolimus-eluting stent and in 11.5% for Xience everolimus-eluting stent ( P =0.55). Rates of cardiac death (3.9% versus 3.8%; P =0.88), target vessel myocardial infarction (3.2% versus 2.5%; P =0.43), and clinically indicated target lesion revascularization (5.2% versus 6.5%; P =0.30) did not differ significantly between the 2 devices. The rate of definite or probable stent thrombosis was infrequent and similar between the 2 arms (1.2% versus 1.5%; P =0.64). The 90-day landmark analysis showed no significant difference in device-oriented composite end point between the 2 groups after polymer degradation of MiStent. The risk of patient-oriented composite end point was comparable between the 2 groups (22.7% versus 22.9%; P =0.34). Conclusions: In the DESSOLVE III trial, early safety and efficacy with MiStent sirolimus-eluting bioabsorbable polymer-coated stent are confirmed at a longer term follow-up when compared with Xience everolimus-eluting permanent polymer-coated stent in a large all-comers population. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02385279.