When Glanzmann thrombasthenia encounters antithrombin defi ciency: how do we balance the risk and benefi t of antithrombotic therapy?

Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).

An extended analysis of cardiovascular benefits of indoor air filtration intervention among elderly:a randomized crossover trial(Beijing indoor air purifier study,BIAPSY)

Objective Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results In the analysis,average levels of indoor PM with aerodynamic diameters<2.5µm(PM2.5)decreased significantly by 59.2%(from 59.6 to 24.3µg/m3,P<0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by−84.6%(95%confidence interval[CI]:−90.7 to−78.6),growth differentiation factor-15 by−48.1%(95%CI:−31.2 to−25.6),osteoprotegerin by−65.4%(95%CI:−56.5 to−18.7),interleukin-4 by−46.6%(95%CI:−62.3 to−31.0)and myeloperoxidase by−60.3%(95%CI:−83.7 to−3.0),respectively.Conclusion Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable populations at risks.

Animal exercise studies in cardiovascular research:Current knowledge and optimal design--A position paper of the Committee on Cardiac Rehabilitation,Chinese Medical Doctors’Association

Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated.Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection.However,standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective,high-quality animal studies using exercise to prevent and treat cardiovascular diseases.In our review,we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training,emphasizing the appropriate measurements and analysis in these chronic exercise models.We also provide recommendations for optimal design of animal exercise studies in cardiovascular research,including the choice of exercise models,control of exercise protocols,exercise at different stages of disease,and other considerations,such as age,sex,and genetic background.We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.

An analysis of patients receiving emergency CAG without PCI and the value of GRACE score in predicting PCI possibilities in NSTE-ACS patients

Background There are patients who underwent emergency coronary angiography （CAG） but did not receive percutaneous coronary intervention （PCI）. The aim of this study was to analyze these reasons. Methods This is a single-center retrospective study. We recruited 201 consecutive patients who received emergency CAG but did not receive PCI. To investigate the value of the Global Registry of Acute Coronary Events （GRACE） score in predicting PC1 possibilities in non-ST segment elevation acute coronary syndrome （NSTE-ACS） pa- tients, we recruited 80 consecutive patients who presented with NSTE-ACS and received emergency CAG as well as emergency PC1. Re- sults Among the 201 patients who received emergency CAG but did not receive PCI, 26% patients had final diagnosis other than coronary heart disease. In the patients with significant coronary artery stenosis, 23 patients （11.5%） were recommended to coronary artery bypass grafting （CABG）, one patient （0.5%） refused PCI; 13 patients （6.5%） with significant thrombus burden were treated with glycoprotein IIb/IIIa receptor antagonist; 74 patients （36.8%） were treated with drug therapy because no severe stenosis （〉 70%） was present in the crime vessel. Moreover, 80 of the 201 patients were presented with NSTE-ACS （excluding those patients with final diagnosis other than coronary heart disease, excluding those patients planned for CABG treatment）, referred as non PCI NSTE-ACS. When comparing their GRACE scores with 80 consecutive patients presented with NSTE-ACS who received emergency CAG as well as emergency PCI （referred as PCI NSTE-ACS）, we found that PCI NSTE-ACS patients had significantly higher GRACE scores compared with non PCI NSTE-ACS patients. We then used Receiver Operator Characteristic Curve （ROC） to test whether the GRACE score is good at evaluating the possibilities of PCI in NSTE-ACS patients. The area under the curve was 0.854 ~ 0.030 （P 〈 0.001）, indicating good predictive value. Furthermore, we analyzed results derived from ROC statistics, and found that a GRACE score of 125.5, as a cut-off, has high sensitivity and specificity in evaluating PCI possibilities in NSTE-ACS patients. Conclusions Our findings indicate that the GRACE score has predictive value in determining whether NSTE-ACS patients would receive PCI.

Prognostic value of coronary artery calcium score in patients with stable an-gina pectoris after percutaneous coronary intervention

Objectives To evaluate the prognostic value of the coronary artery calcium （CAC） score in patients with stable angina pectoris （SAP） who underwent percutaneous coronary intervention （PCI）. Methods A total of 334 consecutive patients with SAP who underwent first PCI following multi-slice computer tomography （MSCT） were enrolled from our institution between January 2007 and June 2012. The CAC score was calculated according to the standard Agatston calcium scoring algorithm. Complex PCI was defined as use of high pressure bal-loon, kissing balloon and/or rotablator. Procedure-related complications included dissection, occlusion, perforation, no/slow flow and emer-gency coronary artery bypass grafting. Main adverse cardiac events （MACE） were defined as a combined end point of death, non-fatal myo-cardial infarction, target lesion revascularization and rehospitalization for cardiac ischemic events. Results Patients with a CAC score〉300 （n=145） had significantly higher PCI complexity （13.1%vs. 5.8%, P=0.017） and rate of procedure-related complications （17.2%vs. 7.4%, P=0.005） than patients with a CAC score≤300 （n=189）. After a median follow-up of 22.5 months （4-72 months）, patients with a CAC score≤300 differ greatly than those patients with CAC score＆gt;300 in cumulative non-events survival rates （88.9 vs. 79.0%, Log rank 4.577, P=0.032）. After adjusted for other factors, the risk of MACE was significantly higher [hazard ratio （HR）：4.3, 95%confidence inter-val （95%CI）：2.4-8.2, P=0.038] in patients with a CAC score〉300 compared to patients with a lower CAC score. Conclusions The CAC score is an independent predictor for MACE in SAP patients who underwent PCI and indicates complexity of PCI and proce-dure-related complications.

Comparison of intraosseous access and central venous catheterization in Chinese adult emergency patients: A prospective, multicenter, and randomized study

BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.

A case of applying left bundle branch pacing combined with atrioventricular node ablation to treat atrial fibrillation-induced heart failure

The core treatment of rapid arrhythmiainduced heart failure(HF)is to control the ventricular rate to an optimized lower level,which is usually achieved with various anti-arrhythmic drugs.However,arrhythmias may not respond well to pharmaceutical treatment for various reasons.Iatrogenic atrioventricular(AV)node ablation needs to be performed under these extreme conditions to lower the patient’s heart rate.

Perspectives of genetic management strategy for inherited cardiovascular diseases in China

Inherited cardiovascular diseases(CVDs)threaten human health and pose an enormous economic burden worldwide.Genetic alteration is a major risk factor for many CVDs.These disorders are usually controlled by a pair of alleles,affecting offspring according to the Mendelian principle,regardless of isolated primary damage or secondary injury from other syndromes or deficiency.To date,there are hundreds of inherited CVDs.With advances in nextgeneration sequencing(NGS)technologies,rapid and accurate molecular diagnosis of patients with inherited CVDs is clinically practical.Besides,great improvements have been made in recent years,and targeted therapy and assist devices have been used in clinical practice.Yet there is still no totally efficient strategy for dealing with inherited CVDs.Accordingly.

Analysis of risk factors for early stent thrombosis in the Chinese population:A multicenter restrospective study

BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.

Animal models of coronary heart disease

Cardiovascular disease,predominantly coronary heart disease and stroke,leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions.The dominant pathologic foundation for cardiovascular disease is atherosclerosis and,as to coronary heart disease,coronary atherosclerosis and resulting lumen stenosis,even total occlusions.In translational research,several animals,such as mice,rabbits and pigs,have been used as disease models of human atherosclerosis and related cardiovascular disorders.However,coronary lesions are either naturally rare or hard to be fast induced in these models,hence,coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions,thus unrepresentative of human coronary heart disease progression and pathology.In this review,we describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.

Hige namine as a Potential Pharmacologic Stress Age nt in the Detection of Coro nary Artery Disease

Myocardial perfusion imaging(MPI) is valuable for the diagnosis,prognosis,and management of coronary artery disease(CAD).The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents.However,these agents have contraindications and may cause adverse effects in some patients.Thus,other stress agents feasible for more patients are required.Higenamine(HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction.It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies.This review summarizes the application of HG on MPI,including its mechanism of action,stress protocol,efficacy,and safety.

Normalization of plasma growth hormone alleviated malignant ventricular tachycardia in acromegaly

Acromegaly is an insidious endocrine disease character- ized by chronic elevation of growth hormone （GH） and insulin-like growth factor-1 （IGF-1）.Ell Persistent excess se- cretion of GH and IGF-1 damages both cardiac structure and function, leading to acromegalic cardiomyopathy, which is one of the most common causes of increased mortality in acromegaly and can result in an average of 10-year reduction in life expectancy.I2＇31 In patients with acromegaly, approximately 3% have been reported having a unique cardiomyopathy characterized by biventricular hypertrophy, myocardial necrosis, lymphocytic infiltration, interstitialfibrosis.

Early identification of STEMI patients with emergency chest pain using lipidomics combined with machine learning

OBJECTIVES To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction(STEMI)and patients with emergency chest pain and excluded coronary artery disease(CAD),and establish the predictive model which could predict STEMI in the early stage.METHODS We conducted a single-center,nested case-control study using the emergency chest pain cohort of Peking Univer-sity Third Hospital.Untargeted lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid molecules.RESULTS Fifty-two STEMI patients along with 52 controls were enrolled.A total of 1925 lipid molecules were detected.There were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group,while in the negative ion mode,there were 73 differentially expressed lipid molecules.In the positive ion mode,the differentially expressed lipid subclasses were mainly diacylglycerol(DG),lysophophatidylcholine(LPC),acylcarnitine(CAR),lysophospha-tidyl ethanolamine(LPE),and phosphatidylcholine(PC),while in the negative ion mode,significantly expressed lipid subclasses were mainly free fatty acid(FA),LPE,PC,phosphatidylethanolamine(PE),and phosphatidylinositol(PI).LASSO regression se-lected 22 lipids while XGBoost combined with greedy algorithm selected 10 lipids.PC(15:0/18:2),PI(19:4),and LPI(20:3)were the overlapping lipid molecules selected by the two feature screening methods.Logistic model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set(AUC:0.972)and an internal validation set(AUC:0.967).In 19 STEMI patients with normal cardiac troponin,18 patients were correctly diagnosed using lipid model.CONCLUSIONS The differentially expressed lipids were mainly DG,CAR,LPC,LPE,PC,PI,PE,and FA.Using lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish model could accurately predict STEMI even in the more earlier stage.

Development and validation of a nomogram predicting oneyear mortality in patients undergoing percutaneous coronary intervention

OBJECTIVE To formulate a nomogram to predict the risk of one-year mortality after percutaneous coronary intervention(PCI)based on a large-scale real-world Asian cohort.METHODS This study cohort included consecutive patients undergoing PCI in the National Center for Cardiovascular Diseases of China.The endpoint was all-cause mortality.Least absolute shrinkage and selection operator Cox regression and backward stepwise regression were used to select potential risk factors.A nomogram based on the predictors was accordingly constructed to predict one-year mortality.The performance of the nomogram was evaluated.Patients were stratified into low-,intermediate-and high-risk groups according to the tertile points in the nomogram and compared by the Kaplan-Meier analysis.RESULTS A total of 9603 individuals were included in this study and randomly divided into the derivation cohort(60%)and the validation cohort(40%).Six variables were selected to formulate the nomogram,including age,renal insufficiency,cardiac dysfunction,previous cerebrovascular disease,previous PCI,and TIMI 0–1 before PCI.The area under the curve of this nomogram regarding one-year mortality risks were 0.792 and 0.754 in the derivation cohort and validation cohort,respectively.Kaplan-Meier curve successfully stratified the patients according to three risk groups.This nomogram calibrated well and exhibited satisfactory clinical utility in the decision curve analysis.CONCLUSIONS This study developed and validated a simple-to-use nomogram predicting one-year mortality risk in Asian patients undergoing PCI and could help clinicians make risk-dependent decisions.

Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

Risk factors for cardiovascular disease in the Chinese population:recent progress and implications

Cardiovascular disease(CVD)is the leading cause of death in both urban and rural areas of China.The current evidence regarding CVD risk factors was primarily established in Western countries,with limited generalizability to the Chinese population.In China,a growing number of population-based prospective cohort studies have emerged that have yielded substantial research data on CVD risk factors in the past five years.The research studies have covered biological risk factors(e.g.,blood lipids,blood pressure,blood glucose,adiposity),lifestyle risk factors(e.g.,smoking,alcohol,diet,physical activity),environmental risk factors(e.g.,ambient and indoor air pollution),and risk prediction.This study aimed to systematically review the research progress on CVD risk factors in the Chinese population in the past five years.Prospective studies in China have identified biological,lifestyle,and environmental risk factors for CVD and its main subtypes,along with some protective factors unique to the Chinese(e.g.,spicy food and green tea).This review aimed to provide high-quality evidence for achieving the Outline of Healthy China 2030,developing disease prevention guidelines and measures,and deepening efforts for popularization of health knowledge.

The mechanism and therapy of aortic aneurysms

Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.

A time sequential microfluid sensor with Tesla valve channels

The concentration of biomarkers in sweat can be used to evaluate human health,making efficient sweat sensing a focus of research.While flow channel design is often used to detect sweat velocity,it is rarely incorporated into the sensing of biomarkers,limiting the richness of sensing results.In this study,we report a time sequential sensing scheme for uric acid in sweat through a sequential design of Tesla valve channels.Graphene electrodes for detecting uric acid and directional Tesla valve flow channels were fabricated using laser engraving technology to realize time sequential sensing.The performance of the channels was verified through simulation.The time sequential detection of uric acid concentration in sweat can help researchers improve the establishment of human health management systems through flexible wearable devices.