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Pathological albuminuria (PAU) (urinary albumin creatinine ratio [UACR] ≥30 mg/g) is an independent risk factor of cardiovascular disease. PAU is more prevalent in men than women. We aimed to compare the association of PAU and the early phase of subclinical atherosclerosis (SA) between sexes.1228 subjects aged 50-90 years were stratified by sex and UACR (normal or PAU). SA was defined as mean carotid intima-media thickness ≥75th percentile of the cohort. Demographics and SA prevalence were compared between groups. Multivariate logistic regression was performed to assess the relationship between PAU and SA.Both men and women with PAU had increased prevalence of hypertension, anti-hypertensive therapy, and metabolic syndrome than controls. Men with PAU were older and had greater waist circumference and total body fat percentage. Sex disparity was observed in associations between waist-to-height ratio, total body fat, and UACR. After adjusting for traditional risk factors, multivariate logistic regression disclosed that PAU was independently associated with SA in men (adjusted odds ratio 1.867, 95% CI 1.066-3.210) but not in women.The relationship of PAU and SA differed between sexes. This result may highlight the need for sex-specific risk management strategies to prevent atherosclerosis.

Amyloidosis cardiomyopathy is a rare and underdiagnosed disease characterized by amyloid fibril deposition in the myocardium. The diagnosis of cardiac amyloidosis is often delayed due to a lack of awareness and the necessity of biopsy to confirm the diagnosis. Recent advances in cardiovascular imaging modalities have enhanced earlier recognition of this disease. A 66-year-old man experiences progressive shortness of breath for two weeks. Laboratory testing was significant for an elevation of cardiac biomarkers (creatine kinase: 522 U/L, troponin I: 0.10 ng/mL) and NT-pro-BNP (5074 pg/mL). He was diagnosed with acute coronary syndrome and received stent deployment. Nonetheless, progressive shortness of breath recurred in 2 months. Transthoracic echocardiography (TTE) demonstrated an increased left ventricular (LV) wall thickness with apical sparing. Cardiac magnetic resonance (CMR) imaging demonstrated high native T1 value, increased extracellular volume fraction as well as diffused subendocardial late gadolinium enhancement. Technetium-99m pyrophosphate (99mTc-PYP) scintigraphy, endomyocardial biopsy (EMB), and the genetic study confirmed the diagnosis of wild-type transthyretin amyloidosis (ATTRwt). The nonspecific clinical manifestations, lack of diagnostic biomarkers, and the rarity of systemic amyloidosis usually lead to delayed diagnosis and treatment. Our objective is to emphasize the role of multimodalities imaging in reducing delays to the diagnosis of cardiac amyloidosis.

Background: Frailty is a common geriatric syndrome related to multiple adverse outcomes. Sex differences in its prevalence and impact on mortality remain incompletely understood. Methods: This study was conducted with data from the I-Lan Longitudinal Aging Study, in which community-dwelling subjects aged > 50 years without coronary artery disease or diabetes were enrolled. Sex disparities in phenotypically defined frailty and sex–morality predictor interactions were evaluated. Sex- and frailty-stratified analyses of mortality were performed. Results: The sample comprised 1371 subjects (51.4% women, median age 61 years). The median follow-up period was 6.3 (interquartile range, 5.8–7.0) years. The frailty prevalence did not differ between men (5.3%) and women (5.8%). Frail individuals were older and less educated and had poorer renal function than did non-frail individuals. Body composition trends differed between sexes, regardless of frailty. Relative to non-frail men, frail men had significantly lower body mass indices (BMIs; 24.5 vs. 23.4 kg/m2, p = 0.04) and relative appendicular skeletal muscle masses (7.87 vs. 7.05 kg/m2, p < 0.001). Frail women had significantly higher BMIs (25.2 vs. 23.9 kg/m2, p = 0.02) and waist circumferences (88 vs. 80 cm, p < 0.001) than did non-frail women. Frailty was an independent mortality predictor for men only [hazard ratio (95% confidence interval) = 3.395 (1.809–6.371), psex–frailty interaction = 0.03]. Conclusion: Frailty reflected poorer health in men than in women in the present cohort. This study revealed sex disparities in the impact of frailty on mortality among relatively healthy community-dwelling older adults.

BACKGROUND Galectin-1 is a glycan-binding protein with broad anti-inflammatory properties. Left ventricular diastolic dysfunction (DD) is associated with heart failure and mortality. The pathophysiology of DD is complex and our study aimed to investigate the associations between serum galectin-1 level, DD, and heart failure with preserved ejection fraction (HFpEF). METHODS Patients with symptoms of angina pectoris were enrolled. Serum galectin-1 levels and echocardiography were assessed. The study endpoint was a composite of all-cause mortality or new-onset HFpEF. RESULTS In total, 258 patients were enrolled (63% male; mean age 68±12 years) and grouped into tertiles based on galectin-1 levels. Patients in the highest galectin-1 group had increased left ventricular mass indexes, left atrial diameters, and prevalence of DD compared to those in the lower tertiles (all p

Background: The Xeltis biorestorative transcatheter heart valve (BTHV) leaflets are made from an electrospun bioabsorbable supramolecular polycarbonate-urethane and are mounted on a self-expanding nitinol frame. The acute haemodynamic performance of this BTHV was favourable. Aims: We sought to demonstrate the preclinical feasibility of a novel BTHV by evaluating the haemodynamic performances of five pilot valve designs up to 12 months in a chronic ovine model. Methods: Five design iterations (A, B, B', C, and D) of the BTHV were transapically implanted in 46 sheep; chronic data were available in 39 animals. Assessments were performed at implantation, 3, 6, and 12 months including quantitative aortography, echocardiography, and histology. Results: At 12 months, greater than or equal to moderate AR on echocardiography was seen in 0%, 100%, 33.3%, 100%, and 0% in the iterations A, B, B', C, and D, respectively. Furthermore, transprosthetic mean gradients on echocardiography were 10.0±2.8 mmHg, 19.0±1.0 mmHg, 8.0±1.7 mmHg, 26.8±2.4 mmHg, and 11.2±4.1 mmHg, and effective orifice area was 0.7±0.3 cm2, 1.1±0.3 cm2, 1.5±1.0 cm2, 1.5±0.6 cm2, and 1.0±0.4 cm2 in the iterations A, B, B', C, and D, respectively. On pathological evaluation, the iteration D demonstrated generally intact leaflets and advanced tissue coverage, while different degrees of structural deterioration were observed in the other design iterations. Conclusions: Several leaflet material iterations were compared for the potential to demonstrate endogenous tissue restoration in an aortic valve in vivo. The most promising iteration showed intact leaflets and acceptable haemodynamic performance at 12 months, illustrating the potential of the BTHV.

Background Insulin resistance (IR) is a known risk factor for cardiovascular disease (CVD) in non-diabetic patients through the association of hyperglycemia or associated metabolic factors. The triglyceride glucose (TyG) index, which was defined by incorporating serum glucose and insulin concentrations, was developed as a surrogate marker of insulin resistance. We aimed to investigate the association between the TyG index and the early phase of subclinical atherosclerosis (SA) between the sexes. Methods The I-Lan Longitudinal Aging Study (ILAS) enrolled 1457 subjects aged 50–80 years. For each subject, demographic data and the TyG index {ln[fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)]/2} were obtained. Patients were further stratified according to sex and the 50th percentile of the TyG index (≥ 8.55 or < 8.55). SA was defined as the mean carotid intima-media thickness (cIMT) at the 75th percentile of the entire cohort. Demographic characteristics and the presence of SA were compared between the groups. Logistic regression analysis was performed to assess the relationship between TyG index and SA. Results Patients with a higher TyG index (≥ 8.55) had a higher body mass index (BMI), hypertension (HTN) and diabetes mellitus (DM). They had higher lipid profiles, including total cholesterol (T-Chol) and low-density lipoprotein (LDL), compared to those with a lower TyG index (p = 0.045] but not in non-diabetic men. The TyG index was not associated with the presence of SA in diabetic patients, irrespective of sex. Conclusion A high TyG index was significantly associated with SA and gender disparity in non-diabetic patients. This result may highlight the need for a sex-specific risk management strategy to prevent atherosclerosis.

This study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).Quantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.Fourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).In vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was -1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.In vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair.

Sarcopenia is a clinical syndrome that features muscle atrophy and weakness, and has been associated with cardiovascular events and poor clinical outcomes. Recently, the sarcopenia index (SI) was developed as a simple screening tool based upon the serum creatinine to cystatin C (CysC) ratio. We investigated the association between SI and the prevalence of major adverse cardiovascular events (MACE) in patients with obstructive CAD.Between January 2010 and December 2018, patients with angina pectoris and obstructive CAD requiring coronary artery intervention were enrolled. Serum levels of CysC and other biomarkers were assessed. Patients were divided into two groups according to the SI ([Cr/CysC] x 100). Demographic characteristics and clinical outcomes of the two groups were evaluated. A total of 427 patients (79.6% men, mean age 69.55 ± 12.04 years) were enrolled. Patients with SI 120 (n = 214, 28%) were older, more likely to be of the female gender, and to have more hypertension and congestive heart failure (all p 0.05). The prevalence of major adverse cardiovascular events (MACE) composed of myocardial infarction, stroke, and all-cause mortality was higher in patients with lower SI (p = 0.026). After adjusting for potential confounding factors, multivariate Cox regression (hazard ratio 2.08, p = 0.045) and Kaplan-Meier analyses (log-rank p = 0.0371) revealed that lower SI was significantly associated with a higher prevalence of MACE.Serum creatinine to cystatin C ratio (SI) may be a useful surrogate marker to predict the future prevalence of MACE in patients with obstructive CAD.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

BackgroundCoronary artery disease (CAD) is one of the leading causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), who are at a greater risk of acute myocardial infarction (AMI) and sudden cardiac death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular events and mortality in T2DM patients with a risk of cardiovascular disease. This study aimed to investigate the effect of SGLT2 inhibitor use on the adverse cardiovascular and renal outcomes in T2DM patients with AMI.MethodsA total of 1,268 patients admitted to the Coronary Care Unit due to AMI were retrospectively screened.Patients taking SGLT2 inhibitors before or during the index AMI hospitalization were assigned as group 1. Patients who never received SGLT2 inhibitors were assigned as group 2. Patients in groups 1 and 2 were matched in a 1:2 ratio, and 198 T2DM patients with stabilized AMI were retrospectively enrolled for the final analysis.ResultsWith a mean follow-up period of 23.5 ± 15.7 months, 3 (4.5%) patients in group 1 and 22 (16.7%) patients in group 2 experienced rehospitalization for acute coronary syndrome (ACS), while 1 (1.5%) patient in group 1 and 7 (5.3%) patients in group 2 suffered sudden cardiac death. The Kaplan–Meier curves demonstrated that the patients in group 1 had a lower risk of adverse cardiovascular outcomes. According to the multivariate analysis, the baseline estimated glomerular filtration rate (eGFR) (P = 0.008, 95% CI: 0.944–0.991) and the use of SGLT2 inhibitors (P = 0.039, 95% CI: 0.116–0.947) were both independent predictors of adverse cardiovascular outcomes. On the other hand, the use of SGLT2 inhibitors was not associated with adverse renal outcomes.ConclusionIn T2DM patients with stabilized AMI, the use of SGLT2 inhibitors was associated with a lower risk of adverse cardiovascular outcomes. In addition, the baseline renal function was also an independent predictor of adverse cardiovascular outcomes.

Galectin-1, a β-galactoside-binding lectin mediating inflammation and neovascularization, is reported to attenuate ventricular remodeling after myocardial infarction. But its role in stable coronary artery disease (CAD) has not been fully elucidated. This study aimed to identify the relationship between the circulating galectin-1 level and the severity of CAD in patients with suspected CAD. Pre-procedure galectin-1 and high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in 834 subjects who underwent scheduled coronary angiography. Subjects were grouped into tertiles of the galectin-1 levels. SYNTAX scores were calculated to evaluate the severity of CAD. All patients were followed until January 2019 or the occurrence of major adverse cardiovascular events (MACE). Patients with higher galectin-1 concentrations were older; had greater prevalence of hypertension, diabetes, chronic kidney disease, and heart failure; and were more likely to present with higher hs-CRP levels and SYNTAX scores. During the follow-up period of 1.3 ± 1.1 years, patients in the highest tertile of galectin-1 were associated with a greater risk of MACE after adjustment for age, sex, comorbidities, co-medications, serum levels of hemoglobin, creatinine, hs-CRP, ejection fraction, SYNTAX scores, and revascularization modalities (adjusted hazard ratio 10.95, 95% confidence interval 2.29–52.47, p = 0.003). Galectin-1 showed better discriminatory performance than hs-CRP, and non-inferior performance to SYNTAX scores, in predicting the incidence of MACE.

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.

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

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.

Objectives: The aim of this study was to assess acute regurgitation following transcatheter aortic valve replacement, comparing different implanted transcatheter heart valves. Background: Regurgitation following transcatheter aortic valve replacement influences all-cause mortality. Thus far, no quantitative comparison of regurgitation among multiple commercially available transcatheter heart valves has been performed. Methods: Aortograms from a multicenter cohort of consecutive 3,976 transcatheter aortic valve replacements were evaluated in this pooled analysis. A total of 2,258 (58.3%) were considered analyzable by an independent academic core laboratory using video densitometry. Results of quantitative regurgitation are shown as percentages. The valves evaluated were the ACURATE (n = 115), Centera (n = 11), CoreValve (n = 532), Direct Flow Medical (n = 21), Evolut PRO (n = 95), Evolut R (n = 295), Inovare (n = 4), Lotus (n = 546), Lotus Edge (n = 3), SAPIEN XT (n = 239), and SAPIEN 3 (n = 397). For the main analysis, only valves with more than 50 procedures (7 types) were used. Results: The Lotus valve had the lowest mean regurgitation (3.5 ± 4.4%), followed by Evolut PRO (7.4 ± 6.5%), SAPIEN 3 (7.6 ± 7.1%), Evolut R (7.9 ± 7.4%), SAPIEN XT (8.8 ± 7.5%), ACURATE (9.6 ± 9.2%) and CoreValve (13.7 ± 10.7%) (analysis of variance p < 0.001). The only valves that statistically differed from all their counterparts were Lotus (as the lowest regurgitation) and CoreValve (the highest). The proportion of patients presenting with moderate or severe regurgitation followed the same ranking order: Lotus (2.2%), Evolut PRO (5.3%), SAPIEN 3 (8.3%), Evolut R (8.8%), SAPIEN XT (10.9%), ACURATE (11.3%), and CoreValve (30.1%) (chi-square p < 0.001). Conclusions: In this pooled analysis stemming from daily clinical practice, the Lotus valve was shown to have the best immediate sealing. This analysis reflects the objective evaluation of regurgitation by an academic core laboratory (nonsponsored) in a real-world cohort of patients using a quantitative technique.

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.

Summary Background & aims Aggressive lipid reduction is recommended for patients with AMI, but reverse epidemiology, the lipid paradox, has been reported in several clinical studies. The cause of lipid paradox remains uncertain, and nutrition is one possible explanation. In this single-center retrospective study, we investigated the relationships between baseline LDL concentrations and clinical outcomes in patients with AMI, stratified by different nutritional status. Methods Totally 409 patients were enrolled for analysis. The Nutritional Risk Index (NRI) was used to estimate the risk of malnutrition. Subjects were grouped into tertiles according to their NRIs. Clinical outcomes were compared among patients with varying NRIs and LDL levels. Results Patients in the lowest NRI tertile had increased incidences of in-hospital mortality, cardiogenic shock, decompensated heart failure, renal failure, and sepsis. This tertile was also associated with increased long-term mortality during the follow-up period of 832 ± 744 days. Mortality was increased among patients with baseline LDL concentrations ≤70 mg/dL in the lowest NRI tertile (log rank test, p = 0.0257), but not in the high or median tertiles. Moreover, baseline LDL level ≤70 mg/dL was an independent risk factor of all-cause mortality (adjusted hazard ratio = 1.73; 95% confidence interval, 1.01–2.94; p = 0.045) in the lowest NRI tertile. Conclusions Lipid paradox was observed in the high-risk of malnutrition population among patients with AMI. Aggressive lipid-lowering therapy is still recommended for patients with AMI and fair nutritional status. However, when treating patients at high risk of malnutrition, the improvement of nutritional status may be more beneficial than strict LDL control.

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.

BACKGROUND Diastolic dysfunction (DD) is a characteristic of heart failure with preserved ejection fraction (HFpEF), which is thought to be caused by cardiac hypertrophy or fibrosis. Activin A is involved in the inflammatory response and myocardial fibrosis, but the relationship between the activin A level and DD remains unclear.Methods and Results:A total of 209 patients with stable angina were enrolled. Serum activin A levels were assessed, and echocardiography and cross-sectional analysis were performed. Among the subjects (65% male; mean age, 70±13 years), 84 (40%) subjects had DD. The subjects were divided into tertiles based on activin A levels. Patients in the high activin A group had enhanced left ventricular mass indexes, medial E/e' ratios, left atrial diameter, and right ventricular systolic pressure compared with those in the lower activin A groups (all P

Trimethylamine N-oxide (TMAO) is a metabolite originated from bacterial metabolism of choline-rich foods. Evidence suggests an association between TMAO and atherosclerosis, but the relationship between TMAO and endothelial progenitor cells (EPCs) remains unclear. This study aimed to identify the relationship between TMAO concentrations, circulating EPCs, and endothelial function in patients with stable angina. Eighty-one stable angina subjects who underwent coronary angiography were enrolled. The circulating EPCs and flow-mediated vasodilation (FMD) were measured to evaluate endothelial function. Plasma TMAO and inflammatory markers, such as hsCRP and IL-1β, were determined. Furthermore, the effect of TMAO on EPCs was assessed in vitro. Patients with lower FMD had significantly decreased circulating EPCs, elevated TMAO, hsCRP, and IL-1β concentrations. Plasma TMAO levels were negatively correlated with circulating EPC numbers and the FMD, and positively correlated with hsCRP, IL-1β concentrations. In in vitro studies, incubation of TMAO in cultured EPCs promoted cellular inflammation, elevated oxidative stress, and suppressed EPC functions. Enhanced plasma TMAO levels were associated with reduced circulating EPCs numbers, endothelial dysfunction, and more adverse cardiovascular events. These findings provided evidence of TMAO’s toxicity on EPCs, and delivered new insight into the mechanism of TMAO-mediated atherosclerosis, which could be derived from TMAO-downregulated EPC functions.

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.

Q-wave myocardial infarction (QWMI) comprises 2 entities. First, a clinically evident MI, which can occur spontaneously or be related to a coronary procedure. Second, silent MI which is incidentally detected on serial electrocardiographic (ECG) assessment. The prevalence of silent MI after percutaneous coronary intervention (PCI) in the drug-eluting stent era has not been fully investigated. The GLOBAL LEADERS is an all-comers multicenter trial which randomized 15,991 patients who underwent PCI to 2 antiplatelet treatment strategies. The primary end point was a composite of all-cause death or nonfatal new QWMI at 2-years follow-up. ECGs were collected at discharge, 3-month and 2-year visits, and analyzed by an independent ECG core laboratory following the Minnesota code. All new QWMI were further reviewed by a blinded independent cardiologist to identify a potential clinical correlate by reviewing clinical information. Of 15,968 participants, ECG information was complete in 14,829 (92.9%) at 2 years. A new QWMI was confirmed in 186 (1.16%) patients. Transient new Q-waves were observed in 28.5% (53 of 186) of them during the follow-up. The majority of new QWMI (78%, 146 of 186) were classified as silent MI due to the absence of a clinical correlate. Silent MI accounted for 22.1% (146 of 660) of all MI events. The prevalence of silent MI did not differ significantly between treatment strategies (experimental vs reference: 0.88% vs 0.98%, p = 0.5027). In conclusion, we document the prevalence of silent MI in an all-comers population undergoing PCI in this large-scale randomized trial. info:eu-repo/semantics/publishedVersion

Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. Objectives: This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. Methods: The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. Results: Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754). Conclusions: Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

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: Angiography-based functional assessment of coronary stenoses emerges as a novel approach to assess coronary physiology. We sought to investigate the agreement between invasive coronary wire-based fractional flow reserve (FFR), resting full-cycle ratio (RFR), and angiography-based vessel FFR (vFFR) for the functional assessment of coronary stenoses in patients with coronary artery disease.Materials and Methods: Between Jan 01, 2018, and Dec 31, 2020, 298 patients with 385 intermediate lesions received invasive coronary wire-based functional assessment (FFR, RFR or both) at a single tertiary medical center. Coronary lesions involving ostium or left main artery were excluded. vFFR analysis was performed retrospectively based on aortic root pressure and two angiographic projections.Results: In total, 236 patients with 291 lesions were eligible for vFFR analysis. FFR and RFR were performed in 258 and 162 lesions, respectively. The mean FFR, RFR and vFFR value were 0.84 ± 0.08, 0.90 ± 0.09, and 0.83 ± 0.10. vFFR was significantly correlated with FFR (r = 0.708, P < 0.001) and RFR (r = 0.673, P < 0.001). The diagnostic performance of vFFR vs. FFR was accuracy 81.8%, sensitivity 77.4%, specificity 83.9%, positive predictive value 69.9%, and negative predictive value 88.5%. The discriminative power of vFFR for FFR ≤ 0.80 or RFR ≤ 0.89 was excellent. Area under the receiver operating characteristic curve (AUC) was 0.87 (95% CI:0.83–0.92) for FFR and 0.80 (95% CI:0.73–0.88) for RFR.Conclusion: Angiography-based vFFR has a substantial agreement with invasive wire-based FFR and RFR in patients with intermediate coronary stenoses. vFFR can be utilized to assess coronary physiology without a pressure wire in a post hoc manner.

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.

Background The clinical effect of atrial fibrillation (AF)-related ischemic cardiovascular events in patients undergoing peritoneal dialysis (PD) remains uncertain. This study aimed to investigate the risk of ischemic events in patients undergoing PD with new-onset AF compared with that in patients without AF and ascertain the association between the CHA2DS2-VASc score and risk of ischemic stroke. Methods This nationwide, population-based cohort study used data from Taiwan's National Health Insurance Research Database from 1998 to 2011 for patients receiving PD with or without new-onset AF. The clinical endpoints included ischemic stroke, all-cause death, and in-hospital cardiovascular death. Results Patients undergoing PD with new-onset AF (N = 505) had significantly higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.98; 95% CI, 1.40-2.80), all-cause death (aHR, 1.61; 95% CI, 1.40-1.85), and in-hospital cardiovascular death (aHR, 1.82; 95% CI, 1.50.2.21) compared with those in patients undergoing PD without AF. After considering in-hospital death as a competing risk, AF remained associated with an increased risk of ischemic stroke (hazard ratio [HR], 1.67; 95% CI, 1.17-2.37). The CHA2DS2-VASc score was associated with the risk of ischemic stroke (HR, 1.28; 95% CI, 1.12-1.46). Conclusion The risks of ischemic stroke, all-cause death, and in-hospital cardiovascular death were significantly higher in patients undergoing PD with AF than those in patients without AF. The CHA2DS2-VASc score remained associated with the risk of ischemic stroke in patients undergoing PD with AF.

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Aims: The aim of this study was to investigate clinical outcomes of patients at high risk of restenosis after implantation of a bioresorbable vascular scaffold (BVS). Methods and results: The COMPARE-ABSORB trial was an investigator-initiated, prospective randomised study. Patients at high risk of restenosis were randomly assigned to receive either a BVS or an everolimus-eluting stent (EES). A dedicated implantation technique was recommended for BVS. The primary endpoint was target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction (TVMI) or clinically indicated target lesion revascularisation at one year. The enrolment was discontinued prematurely because of a high thrombosis and TVMI rate in the BVS arm. A total of 1,670 patients were recruited (BVS 848 patients and EES 822 patients). TLF occurred in 43 patients (5.1%) of the BVS group and 34 patients (4.2%) of the EES group (absolute difference 0.9%, 95% confidence interval [CI]: −1.2%-3.0%, p non-inferiority

Regurgitation following transcatheter aortic valve replacement (TAVR) impacts all-cause mortality. We sought to compare the quantitative regurgitation after TAVR with different transcatheter aortic valves. Pooled analysis of 3,976 TAVR in a multicenter cohort. A total of 2,258 (58.3%) were

Percutaneous coronary intervention with implantation of drug-eluting stents has become the most commonly performed revascularization procedure in patients with symptomatic coronary artery disease. Continuous iterations of coronary devices incorporating changes in platform materials, geometry, strut thickness, drug-release mechanisms and anti-proliferative drugs, have progressively reduced the rate of device-related adverse clinical events, and objective performance criteria have been proposed for clinical and angiographic outcomes of drug-eluting stents. The rate of device success has been recognized as an intra-procedural endpoint to evaluate the mechanical ability to complete a procedure with the specific device assigned by protocol in randomized comparative trials. The European Commission and the U.S. Food and Drug Administration both provide guidance documents including the mechanistic evaluation of coronary stents which recommend operational definitions of device success. While the majority of clinical trials investigating drug-eluting stents have adopted this endpoint definition, inconsistencies in application limit the reliability of comparisons across different trials reporting device success rates. In addition, it is not uncommon that device success rates are not reported by investigators. A consistent definition of device success is essential to allow scientific comparisons of this technical performance endpoint between devices across different trials. Therefore, we performed a systematic evaluation of definitions and reporting of device success in clinical trials. We propose an extended definition as well as considerations for approaching the determination of the device success rates in future percutaneous coronary intervention trials.

IMPORTANCE: Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI). OBJECTIVES: To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies. DESIGN, SETTING, AND PARTICIPANTS: This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019. INTERVENTIONS: Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding. RESULTS: Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045). CONCLUSIONS AND RELEVANCE: Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01813435

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

With the rise and consolidation of the minimalistic approach era for transcatheter aortic valve replacement (TAVR) procedures without general anesthesia, the use of intraprocedural transesophageal or transthoracic echocardiogram (TTE) becomes limited. However, this high-risk group of patients

Aim Frailty is a highly prevalent geriatric syndrome, characterized by increased vulnerability to subsequent morbidity and mortality. The association between frailty and preclinical atherosclerosis remains uncertain. The aim of the present study was to clarify the relationship between frailty, preclinical atherosclerosis and inflammatory markers in older adults. Methods We enrolled 1798 inhabitants of I-Lan County of Taiwan (855 men, 47.5%; mean age 64 ± 9 years, range 50–92 years). Assessment of frailty was based on the Cardiovascular Health Study criteria. Common carotid artery intima-media thickness (CIMT) was determined using carotid Doppler ultrasonography. Results Overall, 955 participants (53.1%) were non-frail, 724 (40.2%) were pre-frail and 119 (6.7%) were frail. Frail and pre-frail participants had significantly increased CIMT, high-sensitivity C-reactive protein, glycated hemoglobin and urine albumin-to-creatinine ratio, but had lower insulin-like growth factor-1 level and decreased femoral neck bone mineral density (BMD). By multivariate analysis, age (OR 2.53, 95% CI 1.92–3.33), C-reactive protein (OR 1.19, 95% CI 1.00–1.42), CIMT (OR 1.27, 95% CI 1.04–1.55) and femoral neck BMD (OR 0.49, 95% CI 0.38–0.65) were independently associated with frailty. Conclusions The present study showed the epidemiology of frailty, and the strong connection to aging, increased CIMT, enhanced inflammation and decreased femoral neck BMD. These results suggested that preclinical atherosclerosis, inflammation and femoral neck BMD were potentially modifiable risk factors for frailty. Geriatr Gerontol Int 2017; ••: ••–••.

Lubricant oils are popularly applied and the spill incidents are seen ubiquitously in the environment, in which the terpane biomarkers are the most abundant compounds and which are the essential compounds in the contaminated soils. We studied the traditional and modified cleanup protocols and developed a negative pressure cleanup device and proposed a more suitable internal standard in the quantitation of biomarkers, wherein the main terpane compounds in a lubricant and soil samples were identified. Surface soil samples were collected in an oil dispatch center where no major spill accidents have been reported in the past decades. Soil samples were studied based on their dry weight quantity and then extracted by using a microwave digestion system. The extracted sample solution was placed in a filter paper and eluted with n-hexane three times and then concentrated by using a nitrogen purge concentration workstation to 1 mL. A lubricant sample was taken without the step of extraction, 0.1 g of lubricants was diluted with 10 mL of hexane, spiked with the surrogate standard, and then concentrated to 1 mL before silica column cleanup procedures. The characteristic fragment ions of terpanes were determined by m/z 177 and 191 in the gas chromatography mass spectrometry (GC/MS) analysis. In the lubricant sample, besides the 17 dominated compounds, another 20 minor terpanes with a concentration ratio (individual/total) of below 1% were also identified using the modified method. In the soil sample study, the result shows that the quantified major terpane concentrations can be increased up to five times by using the modified method. The soil data also shows that the lower molecular weight compound has higher concentration ratios than the other compounds that were eluted at a later time. The results indicated that for the real environmental samples as for the studied soil, the modified method could enhance the detection probability for those weathering effected compounds. The modified cleanup method has successfully improved the identification technology and many overlooked minor biomarkers were revealed in the samples and the minor biomarkers may including the compound that has been popularly used as the surrogate standard. In quantitation, we proposed a more proper internal standard for future research. The results can also be applied to identify other kinds of biomarkers to plan a suitable remediation program for a contaminated site.

Context Although there is evidence to support the beneficial effects of statins on major cardiovascular events, few studies address the protective effect of statins on limb outcome. Objective To investigate whether the use of statin is associated with a risk reduction in lower-extremity amputation in type 2 diabetes mellitus (DM) patients with peripheral arterial disease (PAD). Design Observational cohort study. Setting A nationwide DM database in Taiwan from 2000 to 2011. Patients A total of 69,332 patients aged ≥20 years with DM and PAD were identified. Intervention Patients were divided into three groups: 11,409 patients were statin users, 4430 patients used nonstatin lipid-lowering agents, and 53,493 patients were nonusers. Main outcome measures The primary outcome was lower-extremity amputation. Secondary outcomes were in-hospital cardiovascular death and all-cause mortality. Results Compared with nonusers, statin users were associated with lower risks of lower-extremity amputation [adjusted hazard ration (aHR), 0.75; 95% confidence interval (CI), 0.62 to 0.90], in-hospital cardiovascular death (aHR, 0.78; 95% CI, 0.69 to 0.87), and all-cause mortality (aHR, 0.73; 95% CI, 0.69 to 0.77). In the propensity score matching analysis, the effect of statin on the risk of lower-extremity amputation was consistent. Only statin users were associated with the risk reduction of lower-extremities amputation (HR, 0.77; 95% CI, 0.61 to 0.97) and cardiovascular death (HR, 0.78; 95% CI, 0.68 to 0.89) when taking competing risk of death into consideration. Conclusions Compared with statin nonusers who were never treated with lipid-lowering drugs, this study found that statin users had a lower risk of lower-extremity amputation and cardiovascular death in patients with DM and PAD.

Biodegradable polymer (BP)-coated drug-eluting stents (DES) were developed to try to accelerate vessel healing and potentially allow a shorter period of mandatory dual-antiplatelet therapy (DAPT) compared with patients treated with durable polymer (DP)-coated DES. The optimal duration of DAPT after