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This study aimed to compare the profiles of young and very young patients with coronary artery disease (CAD) and explore the factors associated with acute myocardial infarction (AMI) based on age.Young CAD patients aged between 18 and 44 years diagnosed by angiography were enrolled retrospectively. They were divided into two groups according to age: young CAD was defined as patients aged between 36 and 44 years, and very young CAD was defined as patients aged between 18 and 35 years. Demographic and clinical characteristics of the patients were collected.In total, 9286 patients were included in the final database. Most were assigned to the young CAD group (86.5%), and 1250 (13.5%) had very young CAD. Most demographic and clinical characteristics of the young and very young patients with CAD differed significantly. The proportion of patients with CAD in the total population increased with age, whereas the incidence of AMI showed a decreasing trend. A previous percutaneous coronary intervention (PCI) was negatively associated with AMI. Dyslipidemia, current smoking, and hyperhomocysteinemia were positively associated with AMI in the overall and young population with CAD.The clinical profiles and factors associated with AMI in CAD patients of different ages were significantly different. Lifestyle-related factors were significantly associated with AMI in young patients with CAD.

This review of colchicine, an effective anti-inflammatory agent, examines whether the reduction in ischemic events produced by colchicine translates to a reduction in mortality, the optimal duration of treatment, and the patient populations that benefits the most from colchicine treatment.We performed a comprehensive PubMed database search using the key words colchicine and coronary heart disease on August 23, 2021. We also screened the included reference list of manuscripts.Colchicine's role in the secondary prevention of coronary artery disease has been the focus of recent large-scale randomized controlled trials in chronic coronary syndrome (ie, the Low-Dose Colchicine and Low-Dose Colchicine 2 trials), acute myocardial infarction (the Colchicine Cardiovascular Outcomes Trial and Colchicine in Patients With Acute Coronary Syndrome trial), and after percutaneous coronary intervention (the Colchicine-Percutaneous Coronary Intervention trial).Current evidence suggests that low-dose colchicine (0.5 mg once a day) reduces the risk of cardiovascular events among patients with acute myocardial infarction or chronic coronary syndrome. Colchicine has the potential to become a new standard therapy for the prevention of coronary artery disease-related atherothrombotic events because it is effective and cost-efficient and has a well-tolerated safety profile.

Objective This study aimed to establish a new scoring system that includes histological quantitative features derived from coronary computed tomographic angiography (CCTA) to predict the efficiency of chronic total occlusion percutaneous coronary intervention (CTO-PCI). Methods This study analyzed clinical, morphological, and histological characteristics of 207 CTO lesions in 201 patients (mean age 60.0 [52.0–65.0] years, 85% male), which were recruited from two centers. The primary endpoint was a guidewire successfully crossing the lesions within 30 m. The new predictive model was generated by factors that were determined by multivariate analysis. The CCTA plaque (CTAP) score that included a quantitative plaque characteristic was developed by assigning an appropriate integer score to each independent predictor, then summing all points. In addition, the CTAP score was compared with other predictive scores based on CCTA. Results The endpoint was achieved in 63% of the lesions. The independent predictors included previous CTO-PCI failure, the proximal blunt stump, proximal side branch, distal side branch, occluded segment bending > 45°, and high-density plaque volume (fibrous volume + calcified volume) ≥ 19.9 mm3. As the score increased from 0 to 5, the success rate of the guidewire crossing within 30 m decreased from 96 to 0%. Comparing the CTAP score with other predictive scores, the CTAP score showed the highest discriminant power (c-statistic = 0.81 versus 0.73–0.77, p value 0.02–0.07). The CTAP score showed similar results for procedural success. Conclusion The CTAP score efficiently predicted the guidewire crossing efficiency and procedural success. Key Points • An increase in high-density plaque volume (fibrous + dense calcium) was more probable to reduce the efficiency of crossing and lead to procedural failure. • The new prediction scoring system with the addition of the quantitative characteristics of plaques had an improved predictive ability compared with the traditional prediction scoring system.

Purpose: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. Methods: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients

Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease. The clinical manifestations of CAS include variant angina, myocardial infarction and sudden death. Although endothelial dysfunction and hyperreactivity of vascular smooth muscle cells have been associated with CAS, the underlying mechanisms remain unclear. Thus, there is a long way to go to truly understand the pathogenesis of CAS to formulate effective treatments. This article discusses the pathophysiological mechanisms as well as downstream molecular pathways of CAS, with a focus on potential therapeutic targets.

Summary Background The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. Methods Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). Findings The PRAISE score showed an AUC of 0·82 (95% CI 0·78–0·85) in the internal validation cohort and 0·92 (0·90–0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70–0·78) in the internal validation cohort and 0·81 (0·76–0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66–0·75) in the internal validation cohort and 0·86 (0·82–0·89) in the external validation cohort for 1-year major bleeding. Interpretation A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. Funding None.

Multiple pathophysiological pathways are activated during the process of myocardial injury. Various cardioprotective strategies protect the myocardium from ischemia, infarction, and ischemia/reperfusion (I/R) injury through different targets, yet the clinical translation remains limited. Caveolae and its structure protein, caveolins, have been suggested as a bridge to transmit damage-preventing signals and mediate the protection of ultrastructure in cardiomyocytes under pathological conditions. In this review, we first briefly introduce caveolae and caveolins. Then we review the cardioprotective strategies mediated by caveolins through various pathophysiological pathways. Finally, some possible research directions are proposed to provide future experiments and clinical translation perspectives targeting caveolin based on the investigative evidence.

Background: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI. Methods and results: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27–0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching. Conclusions: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events.

Background: The rate of intracranial haemorrhage after an acute coronary syndrome has been studied in detail in the era of thrombolysis; however, in the contemporary era of percutaneous coronary intervention, most of the data have been derived from clinical trials. With this background, we aim to analyse the incidence, timing, predictors and prognostic impact of post-discharge intracranial haemorrhage in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: We analysed data from the BleeMACS registry (patients discharged for acute coronary syndrome and undergoing percutaneous coronary intervention from Europe, Asia and America, 2003–2014). Analyses were conducted using a competing risk framework. Uni and multivariate predictors of intracranial haemorrhage were assessed using the Fine–Gray proportional hazards regression analysis. The endpoint was 1-year post-discharge intracranial haemorrhage. Results: Of 11,136 patients, 30 presented with intracranial haemorrhage during the first year (0.27%). The median time to intracranial haemorrhage was 150 days (interquartile range 55.7–319.5). The fatality rate of intracranial haemorrhage was very high (30%). After multivariate analysis, only age (subhazard ratio 1.05, 95% confidence interval 1.01–1.07) and prior stroke/transient ischaemic attack (hazard ratio 3.29, 95% confidence interval 1.36–8.00) were independently associated with a higher risk of intracranial haemorrhage. Hypertension showed a trend to associate with higher intracranial haemorrhage rate. The combination of older age (⩾75 years), prior stroke/transient ischaemic attack, and/or hypertension allowed us to identify most of the patients with intracranial haemorrhage (86.7%). The annual rate of intracranial haemorrhage was 0.1% in patients with no risk factors, 0.2% in those with one factor, 0.6% in those with two factors and 1.3% in those with three factors. Conclusion: The incidence of intracranial haemorrhage in the first year after an acute coronary syndrome treated with percutaneous coronary intervention is low. Advanced age, previous stroke/transient ischaemic attack, and hypertension are the main predictors of increased intracranial haemorrhage risk.

BACKGROUND The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Objective We sought to determine the association between mental stress-induced myocardial ischaemia (MSIMI) and quality of life (QoL) in patients with coronary artery disease (CAD) after coronary revascularization. Methods This cohort study involved patients with high-risk MSIMI who received coronary revascularization between Dec 2018 and Dec 2019. Patients who screened positive for depression/anxiety were enrolled in this study. Mental stress was induced by the Stroop Colour and Word Test 1 month after coronary revascularization. All participants underwent single photon emission computed tomography (SPECT) scans at rest and under mental stress. MSIMI was defined as the presence of four abnormal SPECT phenomena. QoL was assessed using the Seattle Angina Questionnaire (SAQ) prior to treatment and 1 month after coronary revascularization. Results Of the 1845 consecutive patients who received coronary revascularization, 590 (31.9%) had depression/anxiety, and 205 agreed to accept the mental stress test. During the average observation period of 33 days, 105 (51.2%) patients exhibited MSIMI. All SAQ subscales showed significant improvement, except for QoL, in the MSIMI group. The QoL score was lower (− 0.2 ± 32.7 vs. 13.1 ± 29.9, P = 0.005), and the proportion of deterioration in QoL was higher (50.5% vs. 31.9%, P = 0.010) in the MSIMI group than in the non-MSIMI group. Those with a deterioration in QoL had approximately twice the rate of MSIMI than those with an improvement in QoL (unadjusted OR: 2.019, 95% CI 1.122–3.634, P = 0.026; adjusted OR: 1.968, 95% CI 1.083–3.578, P = 0.017). Conclusion Among patients with CAD who received coronary revascularization and had depression/anxiety, deterioration in QoL increased the likelihood of MSIMI. Hence, our results indicate that deterioration in QoL is a predictor of MSIMI. Trail Registration ChiCTR2200055792, retrospectively registered, 2022.1.20, www.medresman.org.cn

Aim To study the role of toll-like receptors 4-myeloid differentiation factor 88 (TLR4-Myd88) dependent caveolin-1 (Cav-1) expression modulation in coronary artery spasm (CAS) and explore the underlying pathogenic mechanisms. Methods and results Lipopolysaccharide (LPS) and acetylcholine (Ach) were used to develop the in vitro and in vivo models mimicking the physiological CAS microenvironment. LPS-induced upregulation of Cav-1 expression in mouse coronary and aorta endothelial cells was shown by western blot and immunofluorescence (IF) staining (p Conclusion These findings suggested that Cav-1, which was upregulated by TLR4-Myd88, served as an important modulator of CAS microenvironment establishment in vivo and in vitro, making it a potential pharmacologic target for the treatment of vasospasm via reduced endothelial cell inflammation.

The long-term relative benefit of culprit-only percutaneous coronary intervention (PCI) and staged PCI in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease remains disputable. This study aimed to compare the long-term outcomes of culprit-only PCI and in-hospital staged complete revascularization in real-world patients with STEMI and multivessel coronary artery disease.A total of 452 patients were treated with in-hospital staged complete revascularization (n=133) or culprit-only PCI (n=319) between May 2012 and December 2015 in our center. The primary end point was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, and unplanned revascularization.The median follow-up period was 3.2 years. Overall, treatment with in-hospital staged complete revascularization can reduce the incidence of the primary end point of MACCE in both the overall population [hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.29-0.82] and the propensity-matched cohorts (HR: 0.51; 95% CI: 0.27-0.97). After correction of the possible confounders, staged PCI remained associated with decreased risk of MACCE (HR: 0.56; 95% CI: 0.33-0.96). Besides, the strategy of staged PCI tended to be associated with lower risk of a composite of cardiac death, myocardial infarction, and stroke than culprit-only PCI in multivariable-adjusted analysis (HR: 0.30; 95% CI: 0.09-1.01).In patients with STEMI and multivessel disease undergoing primary PCI, an approach of in-hospital staged complete revascularization was associated with a better 3-year composite outcome compared with culprit-only PCI.

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

Aims The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. Methods and results All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR Conclusion In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Introduction and objectives For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF. Methods Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis. Results Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P = .012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF > 40% (P value for treatment-by-LVEF interaction = .008). For patients with LVEF > 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P = .031). Conclusion The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF > 40% and ST-segment elevation myocardial infarction. In non–ST-segment elevation-ACS patients with LVEF > 40%, further studies are needed to assess the prognostic impact of ACEI/ARB.

Purpose: The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era. Methods and Results: The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients. Conclusions: BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed.

Introduction: Bleeding is an independent risk factor of mortality in patients with acute coronary syndromes (ACS). BleeMACS project focuses on long-term bleeding events after hospital discharge, thus we evaluated gender-related differences in post-discharge bleeding among patients with ACS. Materials and methods: We investigated 13,727 ACS patients treated with percutaneous coronary intervention and discharged on dual antiplatelet therapy (either with clopidogrel or prasugrel/ticagrelor). Endpoint was defined as intracranial bleeding or any other bleeding leading to hospitalization and/or red blood transfusion. Results: Post-discharge bleeding was reported more frequently in females as compared with males (3.7% vs. 2.7%, log-rank P = 0.001). Females (n = 3165, 23%) were older compared to men (69.0 vs. 61.5 years, P < 0.001) and with more comorbidities. Hence, in multivariate analysis female sex was not identified as an independent risk factor of bleeding (HR 1.012, CI 0.805 to 1.274, P = 0.816). Administration of newer antiplatelet agents compared to clopidogrel was associated with over twofold greater bleeding rate in females (7.3% vs. 3.5%, log-rank P = 0.004), but not in males (2.6% vs. 2.7%, log-rank P = 0.887). Differences among females remained significant after propensity score matching (7.2% vs 2.4%, log-rank P = 0.020) and multivariate analysis confirmed that newer antiplatelet agents are independent risk factor for bleeding only in women (HR 2.775, CI 1.613 to 4.774, P < 0.001). Conclusions: Bleeding events occurred more frequently in women, but female sex itself was not independent risk factor. Administration of newer antiplatelet agents was identified as independent risk factor of bleeding after hospital discharge in female gender, but not in male patients.

Background: Currently, drug-eluting balloon (DEB) appears to be an attractive alternative option for the treatment of in-stent restenosis (ISR). Nevertheless, the clinical outcomes of DEB have seldom been compared to those of new-generation drug-eluting stent (DES). Thus, this meta-analysis aimed to evaluate the safety and efficacy of DEB compared to those of new-generation DES in the treatment of ISR. Methods: A comprehensive search of electronic databases including PubMed, EMBASE, and Cochrane Library up to November 2, 2017 was performed to identify pertinent articles comparing DEB to new-generation DES for the treatment of ISR. In addition, conference proceedings for the scientific sessions of the American College of Cardiology, American Heart Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, and EuroPCR were also searched. The primary endpoint was target lesion revascularization (TLR) at the longest follow-up. Dichotomous variables were presented as risk ratios (RRs) with 95% confidence intervals (CIs), while the overall RRs were estimated using the Mantel-Haenszel random-effects model. Results: Five randomized controlled trials (RCTs) and eight observational studies involving 2743 patients were included in the present meta-analysis. Overall, DEB was comparable to new-generation DES in terms of TLR (RR = 1.24, 95% CI: 0.89-1.72, P = 0.21), cardiac death (RR = 1.55, 95% CI: 0.89-2.71, P = 0.12), major adverse cardiovascular event (RR = 1.21, 95% CI: 0.98–1.48, P = 0.07), myocardial infarction (RR = 1.12, 95% CI: 0.72–1.76, P = 0.62), and stent thrombosis (RR = 0.95, 95% CI: 0.38-2.42, P = 0.92). However, DEB was associated with higher risk of all-cause mortality than new-generation DES (RR = 1.65, 95% CI: 1.09-2.50, P = 0.02). This was especially true in the real-world observational studies (RR = 1.79, 95% CI: 1.12-2.88, P = 0.02). In RCTs, however, no significant difference was found between the two treatment strategies in the risk of all-cause mortality. Conclusions: The current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies. Key words: Drug-Eluting Balloon; In-Stent Restenosis; Meta-Analysis; New-Generation Drug-Eluting Stent

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. Methods and results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, PConclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

In order to determine the function of dHAND in a specific subset of cardiomyocyte progenitor cells responsible for the heart and its function in the cellular mechanism of Hand2−/− mouse ventricular hypoplasia, we established an allelic knockout model of dHAND in human embryonic stem cells (hESCs-H9) by an episomal vector-based CRISPR/Cas9 system. This dHAND KO hESC line maintained normal karyotype and typical primed pluripotent human stem cell morphology, and maintained pluripotency, could differentiate into all three germ layers in vivo.

BackgroundRecently, several randomized trials have noted improved outcomes with staged percutaneous coronary intervention (PCI) of nonculprit vessels in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, it remains unclear whether diabetes status affects the outcomes after different revascularization strategies. This study thus compared the impact of diabetes status on long-term outcomes after staged complete revascularization with that after culprit-only PCI.MethodsFrom January 2006 to December 2015, 371 diabetic patients (staged PCI: 164, culprit-only PCI: 207) and 834 nondiabetic patients (staged PCI: 412, culprit-only PCI: 422) with STEMI and multivessel disease were enrolled. The primary endpoint was 5-year major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction (MI), stroke or unplanned revascularization.ResultsThe rate of the 5-year composite primary endpoint for diabetic patients was close to that for nondiabetic patients (34.5% vs. 33.7%; adjusted hazard ratio [HR] 1.012, 95% confidence interval [CI] 0.815–1.255). In nondiabetic patients, the 5-year risks of MACCE (31.8% vs. 35.5%; adjusted HR 0.638, 95% CI 0.500–0.816), MI (4.6% vs. 9.2%; adjusted HR 0.358, 95% CI 0.200–0.641), unplanned revascularization (19.9% vs. 24.9%; adjusted HR 0.532, 95% CI 0.393–0.720), and the composite of cardiac death, MI or stroke (11.4% vs. 15.2%; adjusted HR 0.621, 95% CI 0.419–0.921) were significantly lower after staged PCI than after culprit-only PCI. In contrast, no significant difference was found between the two groups with respect to MACCE, MI, unplanned revascularization, and the composite of cardiac death, MI or stroke in diabetic patients. Significant interactions were found between diabetes status and revascularization assignment for the composite of cardiac death, MI or stroke (Pinteraction = 0.013), MI (Pinteraction = 0.005), and unplanned revascularization (Pinteraction = 0.013) at 5 years. In addition, the interaction tended to be significant for the primary endpoint of MACCE (Pinteraction = 0.053). Moreover, the results of propensity score-matching analysis were concordant with the overall analysis in both diabetic and nondiabetic population.ConclusionsIn patients with STEMI and multivessel disease, diabetes is not an independent predictor of adverse cardiovascular events at 5 years. In nondiabetic patients, an approach of staged complete revascularization is superior to culprit-only PCI, whereas the advantage of staged PCI is attenuated in diabetic patients.Trial registrationThis study was not registered in an open access database

The relative benefit of staged percutaneous coronary intervention (PCI) versus culprit-only PCI in patients with ST-segment elevation myocardial infarction and multivessel coronary disease remains disputable. Therefore, we conducted this study to compare the long-term outcomes of staged complete revascularization and culprit-only PCI in this population. A total of 1,205 patients were treated with staged PCI (n = 576) or culprit-only PCI (n = 629) from January 2006 to December 2015 in our center. After propensity-score matching, 415 pairs of patients were identified, and postmatching absolute standardized differences were10% for all covariates. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction (MI), stroke, or unplanned revascularization. The mean follow-up duration was 5 years. Overall, staged complete revascularization was associated with lower risks of MACCE, MI, unplanned revascularization, and a composite of cardiac death, MI or stroke compared with culprit-only PCI in both overall population and propensity-matched cohorts. In Cox proportional hazards regression analysis, the strategy of staged PCI was consistently a significant predictor of lower incidences of MACCE, MI, unplanned revascularization and a composite of cardiac death, MI, or stroke. However, there was no difference in the risks of MACCE, MI and unplanned revascularization between the 2 approaches for diabetic patients. In conclusion, among patients with ST-segment elevation myocardial infarction and multivessel disease who underwent primary PCI, an approach of staged complete revascularization is superior to culprit-only PCI at 5-year follow-up. Nevertheless, the advantage of staged PCI is attenuated in diabetic patients.

Background Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS). Methods Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS). Results Overall, 13,975 patients were included: mean age was 64.1years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end-point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244–7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients. Conclusions In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis.

Background: There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events. Methods: All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups. Results: Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3–8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group. Conclusions: During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.

Background. Insufficient data are available on the potential benefit of selective aspiration and clinical predictors for no-reflow in STEMI patients undergoing primary percutaneous coronary intervention (PPCI) adjunct with aspiration thrombectomy. Objective. The aim of our study was to investigate clinical predictors for insufficient reperfusion in patients with high thrombus burden treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011 till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy and PPCI were selected and 202 patients with a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study. According to a cTFC value, patients were divided into Group I (cTFC > 40), namely, insufficient reperfusion group; Group II (cTFC ≤ 40), namely, sufficient reperfusion group. Results. Univariate analysis showed that hypertension, multivessel disease, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were negative predictors for insufficient reperfusion. After multivariate adjustment, age ≧ 60 years, hypertension, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were independently associated with insufficient reperfusion in STEMI patients treated with manual aspiration thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was positively associated with improved myocardial reperfusion. Conclusion. Fully identifying risk factors will help to improve the effectiveness of selective thrombus aspiration.

To determine the most accurate and reproducible semi-automated greyscale thresholding technique for quantifying late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMRI), by using positron-emission tomography (PET) as the reference standard in patients with coronary artery chronic total occlusion (CTO).LGE in CMRI, single-photon-emission computed tomography (SPECT), and PET were performed within 1 week in each of 63 patients with known CTO. The presence and quantity of LGE were determined with greyscale thresholds of 2, 4, 5, 6, and 8 standard deviations (SDs) above the mean signal intensity for normal remote myocardium and full width at half maximum (FWHM). The infarcted myocardium was delineated by PET.Sixty-three patients and 1,008 segments were analysed. Based on patient analysis, with PET as the reference standard, the 5 SD method yielded the strongest correlation (r=0.85, p0.0001) compared with the 2 SDs (r=0.42), 4 SDs (r=0.73), 6 SDs (r=0.81), 8 SDs (r=0.71), and FWHM (r=0.69; p0.001 for all comparisons). The 5 SDs threshold quantification showed high interobserver and intra-observer agreement (intraclass correlation coefficient [ICC]=0.90, p0.0001; ICC=0.93, p0.0001, respectively).Semi-automated LGE CMRI greyscale thresholding with 5 SDs above the mean signal intensity for normal remote myocardium yields the strongest correlation to the extent of LGE identified using PET and is highly reproducible in patients with CTO.

Introduction: Coronary microvascular dysfunction (CMVD), highly prevalent among patients with a mental disorder (anxiety or depression), is closely related to adverse cardiac events, including hospitalization, sudden cardiac death, and myocardial infarction. Shexiang Tongxin Dropping Pills (STDP), a traditional Chinese medicine, exerts endothelial protective function by anti-inflammation, anti-oxidative stress, and promoting blood circulation. STDP protects against CMVD in previous fundamental studies. The present trial is aiming at evaluating the effect of STDP on CMVD among depressed or anxious patients with non-obstructive coronary artery disease (NOCAD). Methods and analysis: Seventy-two depressed or anxious patients diagnosed with NOCAD combined with CMVD utilizing coronary artery angiography and stress cardiac magnetic resonance (CMR) will be recruited in the present study. These patients will be randomized into two groups, namely, Nicorandil group (Nicorandil combined with routine medicine), and STDP groups (STDP combined with routine medicine). The change of CMVD status by assessing absolute myocardial blood flow and myocardial reperfusion using stress CMR 3-month after discharge is defined as the primary endpoint. Major adverse cardiac events (MACEs), quality of life (QOL), and metal disorder improvement are defined as the secondary endpoints. Seattle angina questionnaire (SAQ) which is used to assess angina pectoris and QOL will be recorded at 1-, 3-, 6-, 9-, 12-month of follow-up. Seven-item Generalized Anxiety Disorder Scale (GAD-7) and 9-item depression module from the Patient Health Questionnaire (PHQ9) which utilized to evaluate anxiety and depression, respectively, will be recorded at 1-, 3-, 6-, 9-, 12-month of follow-up. This study will first evaluate the efficacy of STDP on CMVD among patients with a mental disorder and NOCAD, and discuss the potential mechanisms, providing therapeutic evidence for the STDP for these patients.

Background The purpose of the work was to evaluate the incremental diagnostic value of free-breathing, contrast-enhanced, whole-heart, 3 T cardiovascular magnetic resonance coronary angiography (CE-MRCA) to stress/rest myocardial perfusion imaging (MPI) and late gadolinium enhancement (LGE) imaging for detecting coronary artery disease (CAD). Methods Fifty-one patients with suspected CAD underwent a comprehensive cardiovascular magnetic resonance (CMR) examination (CE-MRCA, MPI, and LGE). The additive diagnostic value of MRCA to MPI and LGE was evaluated using invasive x-ray coronary angiography (XA) as the standard for defining functionally significant CAD (≥ 50% stenosis in vessels > 2 mm in diameter). Results 90.2% (46/51) patients (54.0 ± 11.5 years; 71.7% men) completed CE-MRCA successfully. On per-patient basis, compared to MPI/LGE alone or MPI alone, the addition of MRCA resulted in higher sensitivity (100% vs. 76.5%, p

The relative safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and coronary artery bypass grafting (CABG) in patients with left ventricular (LV) systolic dysfunction remains controversial; therefore we conducted this meta-analysis to identify the optimal strategy for such cohorts. A comprehensive search of the electronic databases including PubMed, EMBASE, and Cochrane Library from January 1, 2003 to March 1, 2018 was performed to identify the eligible adjusted observational studies. The primary end point was all-cause death during the longest follow-up, and the generic inverse variance random-effect model was used to estimate the pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Eight adjusted observational studies involving 10,268 patients were included. Compared with CABG, PCI with DES was associated with higher risk of all-cause mortality (HR 1.36, 95% CI 1.16 to 1.60), cardiac mortality (HR 2.20, 95% CI 1.63 to 2.95), myocardial infarction (HR 1.69, 95% CI 1.28 to 2.24), and repeat revascularization (HR 4.95, 95% CI 3.28 to 7.46) in patients with coronary artery disease and LV systolic dysfunction. Besides, separate analysis of patients with LV ejection fraction

The impact of coronary collaterals on the prognosis in patients with acute ST-segment elevation myocardial infarction (STEMI) in the era of coronary revascularization remains controversial. The purpose of this meta-analysis was to investigate the effect of coronary collateral on clinical outcomes, especially mortality (≥6 months), in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. Eligible observational studies were selected by searching PubMed, EMBASE, and Cochrane Library up to August 9, 2017. Overall, 14 observational studies involving 10 411 patients were included. Coronary collaterals were found to reduce the risk of long-term mortality (≥6 months; risk ratio [RR]: 0.65, 95% confidence interval [CI]: 0.55-0.76) as well as in-hospital plus 30-day mortality (RR: 0.61, 95% CI: 0.47-0.78) in patients undergoing PCI for STEMI. In addition, pooling the risk-adjusted or propensity-matched data showed a significant reduction in long-term mortality (RR: 0.68, 95% CI: 0.49-0.95) and in-hospital plus 30-day mortality (RR: 0.27, 95% CI: 0.13-0.55) in patients with collateral circulation. However, no significant difference was found in the risk of recurrent myocardial infarction and target vessel revascularization between the 2 groups. Therefore, it was found that coronary collaterals have a beneficial effect on long-term survival (≥6 months) as well as in-hospital plus 30-day survival in patients undergoing primary PCI for STEMI.

Background A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. Methods We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine–Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). Results The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92–2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). Conclusion Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.

Whether the effect of diabetes on patients with unprotected left main coronary artery (ULMCA) disease differs according to different strategies of revascularization was unknown. This study was conducted to evaluate the impact of diabetes on patients with ULMCA disease treated with either percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG).A total of 922 patients with ULMCA disease who received drug-eluting stent (DES) (n = 465) implantation or underwent CABG (n = 457) were retrospectively analyzed. We compared the effects of these 2 treatments on clinical outcomes (death, myocardial infarction, stroke, repeat revascularization, and the composite of death, myocardial infarction, or stroke), according to diabetic status.During the median follow-up of 7.1 years (interquartile range, 5.3 to 8.2 years), no difference was found between PCI and CABG in the adjusted occurrence of death (P = 0.112) and the composite endpoints of death, myocardial infarction, and stroke (P = 0.235). Significantly higher incidence of repeat revascularization (P < 0.001) was observed in the DES group, whereas the CABG group had a significantly higher rate of stroke (P = 0.001). These trends were consistent in both diabetic and nondiabetic patients. We did not observe significant interactions between treatment outcomes and the presence or absence of diabetes after adjustment for covariates (P(interaction) = 0.580 for the composite of death, MI and stroke, P(interaction) = 0.685 for death, P(interaction) = 0.416 for MI, P(interaction) = 0.470 for stroke, and P(interaction) = 0.502 for repeat revascularization).Presence of diabetes was not important for decision-making between CABG and PCI in patients with ULMCA disease.

To investigate the efficacy and safety of stent versus non-stent in treating acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel disease and intermediate stenosis culprit lesions.Between September 2009 and May 2015, 475 acute STEMI patients (time from symptom onset12 hours) with single vessel disease and intermediate stenosis culprit lesions were retrospectively studied at Beijing Anzhen Hospital. The patients were divided into a stent group (n = 308) and non-stent group (n = 167) based on whether they received stent implantation or not during primary coronary angiography.During follow-up, the stent group patients had a lower major adverse cardiac and cerebrovascular event (MACCE) rate than the non-stent group: 5.5% versus 12.0%; P = 0.01; hazard ratio (HR) 0.35 [95% confidence interval (CI): 0.180.69]). The nonfatal myocardial infarction (MI) rate was lower in the stent group (2.9% versus 7.2%, P = 0.03). The cardiac death rate (1.9% versus 3%, P = 0.45) and stroke (0.6% versus 1.8%, P = 0.35) rate were similar between the stent and non-stent groups. The two groups shared similar all cause death rates: 4.9% versus 5.4%, respectively, P = 0.81; HR: 1.23 [95%CI: 0.51-2.99]. The composite ischemia outcome of death/MI/stroke was lower in the stent group (8.1% versus 14.4%, P = 0.02). The stent and non-stent groups had similar repeat revascularization rates (10.1% versus 11.4%, P = 0.67); ischemia driven readmission (19.5% versus 15.0%, P = 0.27), and bleeding (1.3% versus 1.2%, P = 1) rates.Stent implantation has a better efficacy and safety in reducing adverse ischemia events in acute STEMI patients with single vessel disease and intermediate stenosis culprit lesions.

Background Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients. Methods The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI. Results Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68–0.74) in the derivation cohort and 0.72 (95% CI 0.67–0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64–0.66) for PCI patients and 0.63 (95% CI 0.62–0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts. Conclusions The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.gov Identifier : NCT02466854

Objective.The aim of the present study was to investigate the predictive value of neutrophil count for no-reflow in patients with ST-segment elevation myocardial infarction (STEMI) who underwent successful primary percutaneous intervention (PCI).Methods.We conducted a retrospective study of 361 patients diagnosed with acute STEMI between 2011 and 2015. All patients underwent successful PCI within 12 h from the onset of symptoms. Angiographic no-reflow was diagnosed based on a post-PCI thrombolysis in myocardial infarction flow grade ≤ 2 without mechanical obstruction. According to a neutrophil count cut-off determined by receiver operating characteristic curve analysis, patients were divided into two groups: group A (neutrophil count 9/L) and group B (neutrophil count ≥ 9.14 × 109/L).Results.Compared to patients in the normal reflow group, patients with no-reflow had higher neutrophil counts (P<0.05). The incidence rate of no-reflow in group A (18, 9.3%) was significantly lower than that in group B (38). Multivariate logistic regression analysis revealed that a neutrophil count ≥ 9.14 × 109/L was independently predictive for no-reflow (odds ratio = 4.474, 95% confidence interval: 1.610–12.433,P=0.004) after adjusting for potential confounders.Conclusions.A circulating neutrophil count ≥ 9.14 × 109/L is independently associated with no-reflow in patients with acute STEMI following primary PCI.

Background Drug-eluting balloon (DEB) has become an alternative option to drug-eluting stent (DES) for the treatment of in-stent restenosis (ISR). However, the effect of drug-eluting balloon with regular bare-mental stent (BMS) in de novo coronary artery disease (CAD) is unclear. This meta-analysis aimed to evaluate the efficacy of DEB with regular BMS compared to BMS or DES in de novo CAD. Methods Randomized controlled trials (RCTs) assessing the efficacy of DEB+BMS in comparison with BMS or DES were obtained by searching the PubMed, EMBASE, and Cochrane Library databases through January 2016. Primary endpoints were major adverse cardiac events (MACEs) and late lumen loss (LLL). Secondary endpoints included death, myocardial infarction (MI), target lesion revascularization (TLR), stent thrombosis (ST), binary restenosis, and minimum lumen diameter (MLD). Dichotomous and continuous data were presented as odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs), respectively, and analyzed using a random-effects model. Results A total of 14 RCTs involving 2281 patients were included in this meta-analysis. DEB+BMS showed significantly less MACEs (OR: 0.67, 95%CI 0.45 to 0.99, P = 0.04) and reduced LLL (MD: -0.30 mm, 95%CI: -0.48 mm to -0.11 mm, P = 0.001) compared with BMS. Meanwhile, treatment with DEB+BMS had disadvantages over DES in terms of MACEs (OR: 1.94, 95%CI 1.24 to 3.05, P = 0.004), LLL (MD: 0.20 mm, 95%CI: 0.07 mm to 0.33 mm, P = 0.003), TLR (OR: 2.53, 95% CI 1.36 to 4.72, P = 0.003), and MLD (MD: -0.25 mm, 95%CI: -0.42 mm to -0.09 mm, P = 0.003). Conclusions This limited evidence demonstrated that treatment with DEB+BMS appears to be effective in de novo CAD. In addition, DEB+ BMS clearly showed superiority to BMS, but is inferior to DES in the treatment of patients with de novo CAD. Hence, DES (especially new generation DES) should be recommended for patients with de novo CAD.

Aims: The benefit of complete or incomplete percutaneous coronary Intervention (PC in patients with myocardial infarction and multivessel disease remains debated. The aim of our study was to compare a complete vs. a "culprit only" revascularisation strategy hi patients with myocardial infarction distinguishing the different clinical subsets (STEM and NSTEMI) and to provide one-year clinical outcome from the "real-life" BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry. Methods and results: We conducted a multicentre study including all patients with myocardial infarction and multivessel coronary disease included in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronae Syndrome) registry. They were divided into two groups, complete revascularisation (CR) and incomplete revascularisation (IR). The primary end-point was the death rate at one-year follow-up. Secondary end-points were in-hospital repeat myocardial infarction (re-AM1), in-hospital heart failure (111:), major adverse cardiovascular events (MACE) and myocardial infarction at one year. Four thousand five hundred and twenty patients were included in our analysis, with a diagnosis of STEMI in 67.7% and NSTEMI in 32.3%. CR was performed in 27.2% and 42.4%, respectively. At univariate analysis, in-hospital and one-year outcomes were similar between CR and IR hi STEMI patients (all p-values >0.05). In NSTEMI patients, CR was associated with a lower one-year death rate (4.5% vs. 8.5%; 1)p=0.002), re-AMI (3.7% vs. 6.6%; p=0.016) and MACE (8.1% vs. 13.9%; p=0.001). After propensity score matching, CR also reduced events in STEM patients, including one-vear mortality (5.3% vs. 13.8%; p

OBJECTIVE The no-reflow phenomenon is associated with a worse prognosis at follow-up for ST-segment elevation myocardial infarction (STEMI) patients with a primary percutaneous coronary intervention. To date, there is no effective method to predict no-reflow. The aim of this study was to establish a predictive system to evaluate the risk of no-reflow by integrating multiple types of information using Bayesian methods. PATIENTS AND METHODS STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the symptom onset between January 2008 and May 2013 were initially screened from the registry database of Anzhen Hospital (Beijing, China). Baseline clinical data, laboratory studies, and procedural characteristics were recorded. The Bayesian Model and Ten-Factor Model were used and compared with the Single-Factor Models. A receiver operating characteristic curve was used to show the efficacy by presenting both sensitivity and specificity for different cutoff points. RESULTS A total of 1059 consecutive STEMI patients were enrolled. Seventy-nine factors were collected to assess the confidence of the no-reflow phenomenon. The combined likelihood ratios were used to measure the reliability of the no-reflow phenomenon. The area under the curve (AUC) was 0.85 and 0.79 for the Bayesian Model and Ten-Factors Model, respectively, whereas the Single-Factor Model yielded a maximum AUC of 0.67. CONCLUSION The Bayesian Model showed high sensitivity and good specificity in predicting true relations between multiple factors and the no-reflow outcome.

AIM To compare cardiac magnetic resonance imaging (MRI) and positron-emission tomography (PET) assessment of myocardial viability in patients with coronary chronic total occlusion (CTO). MATERIALS AND METHODS Eighty patients with coronary CTO underwent cardiac MRI and PET. Cardiac MRI images were analysed using a 17-segment model, and late gadolinium enhancement (LGE) and wall motion were scored. PET was used to classify myocardial viability via myocardial perfusion and 18F-fluorodeoxyglucose, digital superscript uptake. RESULTS With PET as the reference standard, the sensitivity of cardiac MRI in detecting myocardial viability was 95.3%, specificity was 87.5%, positive predictive value was 96.8%, negative predictive value was 84.2%, and accuracy was 93.8% on a per patient basis. The receiver operator characteristic curve was used to analyse the performance of cardiac MRI in the detection of myocardial viability on a per-patient basis and the area under the curve was 0.910 (95% confidence interval 0.805 to 1). Cardiac MRI had the highest sensitivity and specificity for differentiating viable and non-viable myocardium as defined by PET when the cut-off value of LGE was 50%. The motion consistency and correlation of cardiac MRI and PET were analysed and kappa was 0.788 (r=0.825; p CONCLUSION Compared with PET, cardiac MRI assessment of myocardial viability in patients with coronary CTO has high sensitivity, specificity, and accuracy. Therefore, cardiac MRI can be used as an important method for evaluating myocardial viability in coronary CTO patients.

To study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (, MKC) on platelet aggregation rate and long-term prognosis of patients with acute coronary syndrome after percutaneous coronary intervention (PCI).A total of 236 patients with acute coronary syndrome, who received successful PCI, were randomly assigned to a trial group (116 cases) and a control group (120 cases) according to random numbers; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent forms. In the trial group, the patients were treated with MKC combined with routine medication, and in the control group the patients were treated with routine medication. The therapeutic course for the two groups was 12 months and the follow-up was 12 months. The levels of ADP-induced platelet aggregation rate and serum high-sensitive C-reactive protein (hs-CRP) were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of cardio-/cerebrovascular events was recorded during the 12-month follow-up.Compared with before PCI, the levels of ADP-induced platelet aggregation rate and serum hs-CRP were significantly higher at 12 h after PCI (P0.05). They were significantly reduced after 30-day-treatment of MKC, showing statistical differences when compared with those in the control group (P0.05). During the 12-month follow-up, the incidence of cardio-/cerebrovascular events was significantly lower in the trial group than in the control group (6.9% vs. 12.5%, P0.01).ADP-induced platelet aggregation function was significantly elevated after PCI. MKC improved the prognosis of patients with acute coronary syndrome, possibly through inhibiting the platelet aggregation, fighting against inflammation, and protecting the vascular endothelial function.

Hypertension affects one billion people worldwide and is an independent risk factor for death after acute coronary syndrome (ACS). The aim of this study was to examine the prevalence and medical treatment of hypertension among 1,301 ACS patients enrolled into the Chinese registry of acute coronary events (CRACE) trial. Analyses were performed by gender, with both genders combined and according to international practice. Multivariable models identified factors associated with use of different classes of antihypertensive medication, and examined the correlation between hypertension and gender with mortality. The use of angiotensin‑converting enzyme inhibitors (ACEI), β-blockers, calcium channel blockers (CCBs) and diuretics increased in both genders during management of presenting ACS. Hypertensive men were more likely to have been receiving β-blockers when they were discharged (77.2%) than women (69.2%). Hypertensive women were more likely to have received diuretics when they were discharged (28.4%) than men (22%). ACEI use increased by ~60% (absolute increase) in both women and men as a result of ACS treatment, but remained similar between the genders, and the same phenomenon was observed in the use of CCBs. Moreover, hypertensive women were less likely to receive evidence‑based medication to treat their acute coronary event than men (for women and men, respectively: β-blocker, 69.2 vs. 77.2%; ACEI, 85.8 vs. 87.5%). Hypertension is more prevalent in women than in men with ACS, and its medical management varies with gender, but it has a similar association with mortality in both genders. Opportunities exist to improve medical therapy and outcomes for women with hypertension.

Our objective was to define the most appropriate treatment for acute coronary syndrome (ACS) in patients with malignancy. The BleeMACS project is a worldwide multicenter observational prospective registry in 16 hospitals enrolling patients with ACS undergoing percutaneous coronary intervention. Primary endpoints were death, re-infarction, and major adverse cardiac events (MACE; composite of death and re-infarction) after 1 year of follow-up. The secondary endpoint was bleeding events during follow-up. We performed sub-study analyses according to whether β-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), statins, or proton pump inhibitors (PPIs) were prescribed at discharge. We also calculated the propensity score for optimal medical therapy (OMT; combination of BB, ACEI/ARB, and statins). The study included 926 patients. According to the multivariate analysis, ACEIs/ARBs (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36–1.94; p = 0.03) and statins (HR 0.37, 95 % CI 0.23–0.61; p

The optimal method of coronary revascularization for patients with coronary artery disease (CAD) and left ventricular (LV) systolic dysfunction is unclear. The purpose of this meta-analysis was to compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in these patients. Two investigators independently searched PubMed, EMBASE, and the Cochrane Controlled Trials Register databases for relevant studies. Four prospective and 5 retrospective studies, published before March 2015, involving 6082 patients were included. Compared with PCI, CABG was significantly associated with lower long-term death (odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.70-0.96, P = .01, I2 = 0%), myocardial infarction (OR: 0.58, 95% CI: 0.36-0.95, P = .03, I2 = 44%), and repeat revascularization (OR: 0.17, 95% CI: 0.14-0.22, P < .001, I2 = 32%). The short-term death rate was comparable between CABG and PCI (OR: 2.09, 95% CI: 0.80-5.45, P = .13, I2 = 9%). Coronary artery bypass grafting has long-term benefits compared with PCI in patients with CAD and LV dysfunction.

Background: In the setting of the Acute Coronary Syndrome (ACS), differences in response to prasugrel and ticagrelor between East Asian and European patients have not been investigated yet. Methods: This is a sub-analysis of the "BleeMACS registry". Patients admitted for ACS and underwent PCI from between 2012 and 2014 were stratified first according to their provenance, Europe vs. East Asia (China and Japan), and then by country. The adjusted rate of 1-year serious bleeding - safety end-point-and 1-year death/re-infarction -effectiveness endpoint-of the new P2Y12r inhibitors were compared. Results: Data of 10004 patients in Europe and 2332 patients in East Asia were collected. At baseline prior stroke (6% vs 9%, p

Bleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital events and absence of patients treated with new antiplatelet agents in the current era of widespread use of percutaneous coronary intervention. The BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) project is a multicenter investigator-initiated international retrospective registry that enrolled more than 15 000 patients discharged with a definitive diagnosis of acute coronary syndrome and treated with percutaneous revascularization. The primary end point is the incidence of major bleeding events requiring hospitalization and/or red cell transfusion concentrates within 1 year. An integer risk score for bleeding within the first year after hospital discharge will be developed from a multivariate competing-risks regression. The BleeMACS registry collaborative will allow development and validation of a risk score for prediction of major bleeding during follow-up for patients receiving contemporary therapies for acute coronary syndrome

Objective: We tested the hypothesis that the plasma levels of fibrinogen and macrophage inflammatory protein (MIP)-1β are synergistic predictive markers of the prognosis of intermediate coronary artery lesions. Methods: A prospective study was performed on 670 patients with intermediate coronary artery lesions. Fibrinogen and MIP-1β were measured. Major adverse cardiac event (MACE) was defined as a composite of cardiovascular death, nonfatal myocardial infarction, revascularization and readmission due to angina pectoris. Results: During follow-up, 72 events occurred; 5 patients died, 7 patients suffered a nonfatal myocardial infarction, 11 patients underwent revascularization and 49 patients were readmitted for angina pectoris. In patients with above-median levels of MIP-1β, a 2.62-fold risk of a MACE [95% confidence interval (CI) 1.53–4.48] was predicted compared with patients with below-median levels of MIP-1β. However, the strongest risk prediction was achieved by assessing MIP-1β and fibrinogen together. After adjusting for traditional risk factors, a multivariate Cox proportional hazards analysis showed that patients with both MIP-1β and fibrinogen above the median had a 4.37-fold risk of a MACE (95% CI 1.89–10.11). Conclusion: MIP-1β accurately predicted MACEs. Considering MIP-1β and fibrinogen together may improve long-term risk assessment. These two biomarkers have a synergistic effect for assessing long-term risk in patients with intermediate coronary artery lesions.

Few studies have assessed the incremental usefulness of multimarkers as predictors of cardiovascular events in patients with mild to moderate coronary artery lesions.We examined 9 plasma inflammatory cytokines (cathepsin S, CXCL16, sopluble CD40 ligand, interleukin-10, placental growth factor, GDF15, matrix metalloproteinase 9, monocyte chemoattractant protein-1, and high-sensitivity C-reactive protein) in 964 patients showing mild to moderate lesions and assessed their association with risk of cardiovascular events during 3 years of follow-up (median 17 months).In a backward Cox regression procedure, Cystatin S (hazard ratio [HR]: 1.788, 95% CI: 1.233 to 2.593, P = 0.02), soluble CD40 ligand (HR: 1.255, 95% CI: 1.054 to 1.494, P = 0.011), placental growth factor (HR: 1.194, 95% CI: 0.976 to 1.461, P = 0.035), and GDF15 (HR: 0.725, 95% CI: 0.550 to 0.956, P = 0.023) were significantly related to cardiovascular events. Compared with multimarker score (according to regression coefficients of significant biomarkers) in the lowest two quintiles, patients in the highest quintile had a higher risk of cardiovascular events after adjustment for traditional risk factors (HR: 2.77, 95% CI: 1.30 to 5.87, P = 0.008). Adding the multimarker score to traditional risk factors contributed significantly to the prediction of cardiovascular events (AUC increased from 0.67 to 0.72).A multimarker approach added to the predictive information obtained from traditional risk factors in patients with mild to moderate coronary artery lesions.

Background: Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily and plays an important regulatory role in the skeletal, immune, and vascular systems. Intermediate coronary artery lesions that have a diameter stenosis of approximately 20%–70% might cause serious consequences. However, the prognostic value of plasma OPG levels in patients with intermediate coronary artery lesions has been less reported. Hypothesis: We hypothesized that OPG is a predictive marker of prognosis of intermediate coronary artery lesions. Methods: A prospective study was performed on 890 patients with intermediate (20%–70%) coronary lesions. The median age was 62 years (25th and 75th percentiles, 55 and 70 years, respectively) and 67.2% were male. Fasting blood was sampled at baseline. The primary clinical endpoint was a composite of readmission due to angina pectoris, nonfatal myocardial infarction, revascularization, and cardiovascular death. Results: During a median follow-up of 24 months, events occurred in 11.1% of the patients. Of these patients, 7.9% were readmitted for angina pectoris, 1.5% received revascularization, 0.7% suffered nonfatal myocardial infarction, and 1.0% died. The plasma levels of OPG (median, 5304.7 pg/mL vs 2993.4 pg/mL, P