Efficacy and safety of sacubitril/valsartan after six months in patients with heart failure with reduced ejection fraction and asymptomatic hypotension

BACKGROUND It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure(HF)with reduced ejec-tion fraction(HFrEF)and low systolic blood pressure(SBP).This study aimed to investigate the efficacy and tolerability of sacu-bitril/valsartan in HFrEF patients with SBP<100 mmHg.METHODS&RESULTS An observational study was conducted on 117 patients,40.2%of whom had SBP<100 mmHg wit-hout symptomatic hypotension,and 59.8%of whom had SBP≥100 mmHg in an optimized HF follow-up management system.At the 6-month follow-up,52.4%of patients with SBP<100 mmHg and 70.0%of those with SBP≥100 mmHg successfully rea-ched the target dosages of sacubitril/valsartan.A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP<100 mmHg and SBP≥100 mmHg(1627.5 pg/mL and 1340.1 pg/mL,respectively;P=0.75).The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories,with a 10.8%increase in patients with SBP<100 mmHg(P<0.001)and a 14.0%increase in patients with SBP≥100 mmHg(P<0.001).The effects of sac-ubitril/valsartan on SBP were statistically significant and inverse across both SBP categories(P=0.001),with an increase of 7.5 mmHg in patients with SBP<100 mmHg and a decrease of 11.5 mmHg in patients with SBP≥100 mmHg.No statistically signi-ficant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension,deteriorating re-nal function,hyperkalemia,angioedema,or stroke.CONCLUSIONS Within an optimized HF follow-up management system,sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.

Target versus sub-target dose of renin–angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs)in elderly patients with heart failure(HF)with reduced ejection fraction(HErEF)remains unclear.METHODS PubMed,Embase,and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials(RCTs)and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients(≥60 years)with HErEF.The primary outcome was all-cause mortality.The secondary outcomes were cardiac mortality,HF hospitalization,and the composite endpoint of mortality or HF hospitalization.A meta-analysis was conducted to generate combined hazard ratio(HR)and 95%CI.RESULTS Seven studies(two RCTs and five observational studies)enrolling 16,634 patients were included.A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality(HR=0.92,95%CI:0.87–0.98,I2=21%)and cardiac mortality(HR=0.93,95%CI:0.85–1.00,I2=15%)but not reduced rates of HF hospitalization(HR=0.94,95%CI:0.88–1.01,I2=0)and the composite endpoint(HR=1.03,95%CI:0.91–1.15,I2=51%).However,the target dose of RASIs was associated with a similar primary outcome(HR=0.85,95%CI:0.64–1.14,I2=0)in a subgroup of very elderly patients>75 years of age.CONCLUSIONS Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs.However,the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients>75 years of age.Future high-quality and adequately powered RCTs are warranted.

Chinese consensus on the diagnosis and treatment of immunoglobulin light-chain cardiac amyloidosis

Epidemiology of Amyloid Light-Chain Cardiac Amyloidosis(AL-CA)The annual incidence of amyloid light-chain(AL)amyloidosis is 3-5/million,and the incidence in men is slightly higher than that in women.Approximately,70%of patients with newly diagnosed AL amyloidosis have cardiac involvement.

Trends and challenges of emergency and acute care in Chinese mainland:2005–2017

BACKGROUND:Emergency medical service system(EMSS)is essential in providing acute care services for health conditions.However,trends of emergency and acute care in China haven’t been studied systematically.METHODS:Relevant literature was carefully reviewed,including original and review articles,letters,government reports,yearbooks,both in Chinese and in English.Data on the number of emergency visits,physicians and beds in emergency departments(EDs),and the workforce of prehospital emergency care were summarized and analyzed from China Health and Family Planning Statistical Yearbooks(2006–2018).RESULTS:Over the past decade,the number of ED visits tripled from 51.9 million to 166.5 million;and utilization of pre-hospital emergency care increased from 3.2 million to 6.8 million.In response to rapid increases in demand,the number of licensed emergency physicians raised from 20,058 to 59,409;the beds’number increased from 10,783 to 42,367.For pre-hospital emergency care,the volume of health workforce increased from 3,687 to 8,671,with a 109%increase in the number of physicians from 1,774 to 3,712.However,overcrowding,the long length of stay in EDs,poor work environment,and work exhaustion were still the critical challenges faced by China’s EMSS.CONCLUSIONS:The number of emergency visits has grown with continual capability enhancement during the past decade.However,overcrowding,the long length of stay in EDs,poor work environment,and work exhaustion still need to be solved by China’s EMSS.These fi ndings and comparison with the USA could offer experiences and lessons to EMSS development worldwide,especially for developing countries.

Acellular porcine corneal matrix as a carrier scaffold for cultivating human corneal epithelial cells and fibroblasts in vitro

AIM：To investigate the feasibility of corneal anterior lamellar reconstruction with human corneal epithelial cells and fibroblasts,and an acellular porcine cornea matrix（APCM） in vitro.·METHODS：The scaffold was prepared from fresh porcine corneas which were treated with 0.5%sodium dodecyl sulfate（SDS）solution and the complete removal of corneal cells was confirmed by hematoxylin-eosin（HE）staining and 4’,6-diamidino-2-phenylindole（DAPI）staining.Human corneal fibroblasts and epithelial cells were cultured with leaching liquid extracted from APCM,and then cell proliferative ability was evaluated by MTT assay.To construct a human corneal anterior lamellar replacement,corneal fibroblasts were injected into the APCM and cultured for 3d,followed by culturing corneal epithelial cells on the stroma construction surface for another 10d.The corneal replacement was analyzed by HE staining,and immunofluorescence staining.·R ESULTS：Histological examination indicated that there were no cells in the APCM by HE staining,and DAPI staining did not detect any residual DNA.The leaching liquid from APCM had little influence on the proliferation ability of human corneal fibroblasts and epithelial cells.At 10d,a continuous 3 to 5 layers of human corneal epithelial cells covering the surface of the APCM was observed,and the injected corneal fibroblasts distributed within the scaffold.The phenotype of the construction was similar to normal human corneas,with high expression of cytokeratin 12 in the epithelial cell layer and high expression of Vimentin in the stroma.·CONCLUSION：Corneal anterior lamellar replacement can be reconstructed in vitro by cultivating human corneal epithelial cells and fibroblasts with an acellular porcine cornea matrix.This laid the foundation for the further transplantation in vitro.

Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS

Acetaldehyde dehydrogenase 2(ALDH2)mutations are commonly found in a subgroup of the Asian population.However,the role of ALDH2 in septic acute respiratory distress syndrome(ARDS)remains unknown.Here,we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS.Intriguingly,ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA(cfDNA)and myeloperoxidase(MPO)-DNA than ALDH2WT-ARDS patients.To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS,we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice.In clinically relevant mouse sepsis models,Aldh2-/-mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis,a specific process that releases neutrophil extracellular traps(NETs)from neutrophils.Furthermore,we discovered that NETosis strongly promoted endothelial destruction,accelerated vascular leakage,and exacerbated septic ARDS.At the molecular level,ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4(PAD4)to inhibit NETosis,which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP.Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis.Together,our data reveal a novel ALDH2-based protective mechanism against septic ARDS,and the activation of ALDH2 may be an effective treatment strategy for sepsis.

The Efficacy and Safety of Tolvaptan in Heart Failure Patients with Congestive Signs:A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective:The aim of this study was to investigate the efficacy and safety of tolvaptan,as well as the impact of its treatment dose and duration in heart failure patients with congestive signs.Methods:The PubMed,Embase,Cochrane Library,and ClinicalTrials.gov databases were searched to collect data from all randomized controlled trials(RCT)examining the efficacy and safety of tolvaptan in heart failure patients with congestive signs compared with placebo or blank control until March 4,2021.Urine volume,change in body weight,improvement in dyspnea,and reduction of edema were evaluated as efficacy indicators.All-cause mortality,worsening heart failure,and adverse events were considered safety indicators.The quality of eligible publications was assessed using the Cochrane risk of bias for RCTs.Results:Ten RCTs with 5,980 patients were included in this analysis.Compared with control,tolvaptan significantly reduced weight in the short term(day 1,7 RCTs,weighted mean difference(WMD):-1.09,95%confidence interval(CI):-1.27 to-0.91;day 2,2 RCTs,WMD:-1.67,95%CI:-3.00 to-0.33;day 7,4 RCTs,WMD:-0.95,95%CI:-1.25 to-0.66),increased urine volume(WMD:1,825.72,95%CI:1,438.38-2,213.07),and relieved dyspnea(risk ratio(RR):1.12,95%CI:1.05-1.19)without increasing the mortality rate(RR:0.96,95%CI:0.87-1.06).Furthermore,the weight loss and increase in urine volume were not dose-dependent effects,and prolonged medication did not lead to sustained weight loss.In addition,there seemed to be more adverse events(RR:1.17,95%CI:1.03-1.32)after treatment with tolvaptan.Further analysis revealed that patients treated with tolvaptan were more likely to report thirst(RR:6.09,95%CI:3.37-11.00)and dry mouth(RR:6.36,95%CI:4.09-9.90),as well as develop hypernatremia(RR:12.76,95%CI:3.52-46.32).Conclusions:The meta-analysis shows that tolvaptan can improve congestion with no increase in mortality rate,but should be used to guard against adverse events.Deserve to be mentioned,the number of RCTs included was limited,suggesting that the observed results should be interpreted with caution.Additional robust clinical studies are warranted to validate the present findings.

Trends in mortality of emergency departments patients in China

BACKGROUND: Emergency medical service system (EMSS) in China is becoming more important. However, studies on mortality of emergency departments (EDs) patients in tertiary hospitals and on the trends in mortality of ED patients all over China are stagnant. The objective of this study was to quantify and describe the trends in mortality of ED patients in China. METHODS: Nine tertiary teaching hospitals were selected from tertiary teaching hospitals in different regions. The annual numbers of ED visits and deaths of these hospitals in 2004, 2009 and 2014 were recorded and analyzed. Chi-square test was used to compare the mortality of the EDs’ visits. Moreover, data on the mortality of ED patients in China from 2005 to 2015 were summarized and analyzed from the China Health and Family Planning Statistical Yearbooks (2006–2016). RESULTS: From 2004 to 2014, the overall annual mortalities in EDs increased among the tertiary hospitals (P<0.001). However, the overall annual mortality in EDs all over China decreased from 0.12% in 2005 to 0.08% in 2015. And the mortalities of EDs patients in the eastern, central and western regions of China all decreased. In addition, the average mortality of EDs patients in northern China was obviously higher than that in southern China (P<0.05). CONCLUSION: The ED mortality was increased in tertiary hospitals while decreased all over China during the past decade, which may be partly caused by some critical challenges faced by China’s EMSS, such as overcrowding and long length of stay in EDs of tertiary hospitals.

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenationinduced cardiomyocyte injury

BACKGROUND:Disturbance of mitochondrial fi ssion and fusion(termed mitochondrial dynamics)is one of the leading causes of ischemia/reperfusion(I/R)-induced myocardial injury.Previous studies showed that mitochondrial aldehyde dehydrogenase 2(ALDH2)conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes.However,whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown.METHODS:In the present study,we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation(H/R)as an in vitro model of myocardial I/R injury.RESULTS:Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation(OGD/R),and ALDH2 activation largely decreased the cardiomyocyte apoptosis.Additionally,we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R.Furthermore,we found that ALDH2 dominantly suppressed dynamin-related protein 1(Drp1)phosphorylation(Ser616)and adenosine monophosphate-activated protein kinase(AMPK)phosphorylation(Thr172)but not interfered with the expression levels of mitochondrial shaping proteins.CONCLUSIONS:We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.

Deficiency of programmed cell death 4 results in increased IL-10 expression by macrophages and thereby attenuates atherosclerosis in hyperlipidemic mice

Programmed cell death 4 （Pdcd4） is a newly defined inhibitor of transcription and translation and a tumor suppressor. Recent studies have suggested that Pdcd4 may also be involved in some inflammatory diseases, However, its role in atherosclerosis, a chronic inflammation of the arterial wall, remains to be investigated. Here, we found that Pdcd4 deficiency in mice increased the expression of IL-10 in macrophages and decreased the expression of IL-17 in T cells in the presence of an atherosclerosis-associated stimulator in vitro and in high fat-induced atherosclerotic plaques. Importantly, knocking out Pdcd4 led to a decrease in atherosclerotic lesions in Apoe-/- mice fed a high fat diet. This effect could be partly reversed by blocking IL-10 with a neutralizing antibody but not by the application of exogenous IL-17. Further mechanistic studies revealed that Pdcd4 negatively regulated the expression of IL-10 in an ERK1/2- and p38-dependent manner. These results demonstrate that Pdcd4 deficiency attenuates atherosclerosis in hyperlipidemic mice in part through the upregulation of the anti-inflammatory cytokine IL-10. This indicates that endogenous Pdcd4 promotes atherosclerosis and therefore represents a potential therapeutic target for patients with atherosclerosis.

Mendelian randomization studies on atherosclerotic cardiovascular disease: evidence and limitations

Epidemiological research has revealed a galaxy of biomarkers, such as genes, molecules or traits, which are associated with increased risk of atherosclerotic cardiovascular diseases(ASCVD). However, the etiological basis remains poorly characterized.Mendelian randomization(MR) involves the use of observational genetic data to ascertain the roles of disease-associated risk factors and, in particular, differentiate those reflecting the presence or severity of a disease from those contributing causally to a disease. Over the past decade, MR has evolved into a fruitful approach to clarifying the causal relation of a biomarker with ASCVD and to verifying potential therapeutic targets for ASCVD. In this review, we selected high-quality MR studies on ASCVD, examined the causal relationship of a series of biomarkers with ASCVD, and elucidated the role of MR in validating biomarkers as a therapeutic target by comparing the results from MR studies and randomized clinical trials(RCTs) for the treatment of ASCVD. The good agreement between the results derived by MR and RCTs suggests that MR could be performed as a screening process before novel drug development. However, when designing and interpreting a MR study, the assumptions and limitations inherent in this approach should be taken into account. Novel methodological developments, such as sensitivity analysis, will help to strengthen the validity of MR studies.

Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice

Angiotensin-converting enzyme 2(ACE2)has proven beneficial in attenuating diabetic cardiomyopathy(DCM)but has been found to be a substrate of a disintegrin and metalloprotease protein-17(ADAM17).However,whether ADAM17 plays a role in the pathogenesis and intervention of DCM is obscure.In this study,we created cardiomyocyte-specific knockout of ADAM17(A17^(α-MHCKO))mice,and left ventricular dimension,function,pathology and molecular biology were assessed in ADAM17^(fl/fl) control,A17^(α-MHCKO) control,ADAM17^(fl/fl) diabetic and A17^(α-MHCKO) diabetic mice.Both differentiated H9c2 cells and neonatal rat cardiomyocytes(NRCMs)were used to explore the molecular mechanisms underlying the effect of ADAM17 on DCM.The results showed that protein expression and activity of ADAM17 were upregulated whereas the protein expression of ACE2 was downregulated in the myocardium of diabetic mice.Cardiomyocyte-specific knockout of ADAM17 mitigated cardiac fibrosis and cardiomyocyte apoptosis and ameliorated cardiac dysfunction in mice with DCM.Bioinformatic analyses detected a number of genes enriched in metabolic pathways,in particular the AMPK signaling pathway,expressed differentially between the hearts of A17^(α-MHCKO)and ADAM17^(fl/fl)diabetic mice.The mechanism may involve activated AMPK pathway,increased autophagosome formation and improved autophagic flux,which reduced the apoptotic response in cardiomyocytes.In addition,hypoxia-inducible factor-1α(HIF-1α)might act as an upstream mediator of upregulated ADAM17 and ADAM17 might affect AMPK signaling viaα1 A-adrenergic receptor(ADRA1A).These results indicated that ADAM17 activity and ACE2 shedding were enhanced in DCM,which was reversed by cardiomyocyte-specific ADAM17 knockout.Thus,inhibition of ADAM17 may provide a promising approach to the treatment of DCM.

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers improved the outcome of patients with severe COVID-19 and hypertension

Dear Editor.Hypertension was reportedly the most common coexisting condition of COVID-19 as 15%-31.2%patients with COVID-19 had hypertension,and the incidence of hypertension reached 58.3%in COVID-19 patients requiring ICU care(Wang et al.,2020).However,it remains unclear whether combined hypertension carries an increased risk for a worse outcome in patients with COVID-19 and what clinical factors independently predict death in these patients.

Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

Vulnerable atherosclerotic plaque rupture lead-ing to thrombosis is the major cause of acute coronary syndrome(ACS).Studies on the pathophysiologic mechanism of both ACS and plaque stabilizing treatment are driving the development of animal models of vulnerable plaque.In our laboratory,we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque rupture.Potential mechanisms involved in plaque vulnerability were studied from the inflammation-immunity,proliferation-apoptosis,oxidative stress and biomechanics aspects.Imaging markers and biomarkers were used to detect vulnerable plaques,including high frequency duplex ultrasound,intravascular ultrasound(IVUS),intravascular ultrasound elastography,magnetic resonance imaging(MRI)and inflammatory markers.Effective gene and drug strategies to treat vulnerable plaques were explored.

The role of lipotoxicity in cardiovascular disease

Fatty acids are the primary fuel for cardiac muscle.The physiological equilibrium of lipid uptake and oxidation may aid in the prevention of excessive lipid accumulation.Several pathological states,such as myocardial ischemia,obesity,and insulin resistance,are routinely associated with disorders of lipid metabolism.There is growing evidence that certain types of lipids trigger cardiac lipotoxicity and ultimately heart failure.This review focuses on recent advances in the pathogenesis of lipotoxic cardiomyopathy and the treatment prospects for the repair of cardiac damage caused by lipotoxicity.

The optimal anticoagulation strategy for COVID-19,prophylactic or therapeutic?:a meta-analysis,trial sequential analysis,and meta-regression of more than 27,000 participants

Background:Anticoagulants are promising regimens for treating coronavirus disease 2019(COVID-19).However,whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion.Methods:We comprehensively searched PubMed,Embase,Scopus,Web of Science,Cochrane Library,ClinicalTrials,and MedRxiv databases on April 26,2022.Two independent researchers conducted literature selection and data extraction separately according to predetermined criteria.Notably,this is the first meta-analysis on COVID-19,taking serious consideration regarding the dosage overlap between the 2 comparison groups of prophylactic anticoagulation(PA)and intermediate-to-therapeutic anticoagulation(I-TA).Results:We included 11 randomized controlled trials(RCTs)and 36 cohort studies with 27,051 COVID-19 patients.By analyzing all the RCTs,there was no significant difference in mortality between the PA and I-TA groups,which was further confirmed by trial sequential analysis(TSA)(odds ratio[OR]:0.93;95%confidence interval[CI]:0.71–1.22;P=0.61;TSA adjusted CI:0.71–1.26).The rate of major bleeding was remarkably higher in the I-TA group than in the PA group,despite adjusting for TSA(OR:1.73;95%CI:1.15–2.60;P=0.009;TSA adjusted CI:1.09–2.58).RCTs have supported the beneficial effect of I-TA in reducing thrombotic events.After including all studies,mortality in the I-TA group was significantly higher than in the PA group(OR:1.38;95%CI:1.15–1.66;P=0.0005).The rate of major bleeding was similar to the analysis from RCTs(OR:2.24;95%CI:1.86–2.69;P<0.00001).There was no distinct difference in the rate of thrombotic events between the 2 regimen groups.In addition,in both critical and noncritical subgroups,I-TA failed to reduce mortality but increased major bleeding rate compared with PA,as shown in meta-analysis of all studies,as well as RCTs only.Meta-regression of all studies suggested that there was no relationship between the treatment effect and the overall risk of mortality or major bleeding(P=0.14,P=0.09,respectively).Conclusion:I-TA is not superior to PA for treating COVID-19 because it fails to lower the mortality rate but increases the major bleeding rate in both critical and noncritical patients.

New insights into the roles of RGC-32

During the last few years,the expression patterns and roles of response gene to complement 32(RGC-32)in various cells and diseases have been hot topics.1 RGC-32 can act as a cell cycle regulator and is involved not only in cell proliferation2 but also in cell differentiation.RGC-32 was found to be essential for TGF-β-induced vascular smooth muscle cell differentiation from neural crest cells.3 The RGC-32 expression levels were significantly higher in unstimulated peripheral CD14+cells from hyper-immunoglobulin E syndrome patients compared with those from healthy controls.4 Moreover,RGC-32 was identified to be co-localized with CD68+cells in multiple sclerosis plaques.5 The above studies and importance of monocytes/macrophages in immune regulation drove us to explore the expression and function of RGC-32 in monocytes/macrophages.

An intersegmental single-cell profile reveals aortic heterogeneity and identifies a novel Malat1+vascular smooth muscle subtype involved in abdominal aortic aneurysm formation

The developmental origin,anatomical location,and other factors contribute to aortic heterogeneity in a physiological state.On this basis,vascular diseases occur at different ratios based on position specificity,even with the same risk factor.However,the continuous intersegmental aortic profile has been rarely reported at the single-cell level.To reveal aortic heterogeneity,we identified 15 cell subtypes from five continuous aortic segments by marker genes and functional definitions.

Plasma biomarkers and plaque strain predict long-term cardiovascular events in patients with acute coronary syndrome

To test whether circulating and intracoronary biomarkers and coronary plaque strain have additive values to Global Registry of Acute Coronary Events(GRACE) score for predicting long-term cardiovascular events in ACS patients. One hundred ACS patients were enrolled and the GRACE score and plasma levels and intracoronary gradients of a number of biomarkers were measured. Coronary plaque burden and morphology in non-critical stenotic plaques were determined by intravascular ultrasound(IVUS) technique, and the maximal shear strain(SSmax) and maximal area strain(ASmax) were determined by intravascular ultrasound elastography(IVUSE) technique. Patients were followed for cardiovascular events and the predictive values of clinical characteristics, plasma biomarkers and plaque parameters were compared with GRACE score, and the incremental values of these measurements to the GRACE score were assessed. GRACE score, plasma biomarkers and plaque strain were independent predictors of cardiovascular events. Combination of GRACE score, plasma biomarkers and plaque strains significantly improved the predictive value of the GRACE score alone with the receiver-operating characteristic area increased from0.457 to 0.667(P=0.014). The combination of circulating and intracoronary biomarkers, plaque strain and GRACE score provides a better predictive tool than GRACE score alone in patients with ACS.

Biomarkers with Potential Predictive Value for Cardiotoxicity in Anticancer Treatments

Rapid development of anticancer treatments in recent years has greatly improved prognosis of cancer patients.However,with extension of survival time of cancer patients,various short-term and long-term side effects brought about by anticancer treatments,especially cardiotoxicity,have become increasingly prominent.Nonetheless,at present,there is few diagnostic methods with extremely high sensitivity and specificity to detect and accurately predict whether patients with anticancer treatment will experience cardiovascular complications.Inflammation,fibrosis and oxidative stress are considered to be important mechanisms involved in cardiotoxicity anticancer treatments.The cardiovascular biomarkers having the ability to predict and detect cardiovascular dysfunction earlier than clinical symptoms as well as left ventricular ejection fraction monitored by echocardiography,are of great value to timely treatment adjustment and prognosis evaluation.Cardiac troponin T/I and brain natriuretic peptide/N-terminal prohormone of brain natriuretic peptide have been routinely used in clinical practice to monitor cardiotoxicity,and some new biomarkers such as soluble suppression of tumorigenecity-2,myeloperoxidase,growth differentiation factor-15,galectin-3,endothelin-1,have potential in this area.In the future,larger-scale experimental studies are needed to provide sufficient evidences,and how to detect them quickly and at low cost is also a problem to be dealed with.