Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China / 中华医学杂志(英文版)

BACKGROUND@#Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.@*METHODS@#We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.@*RESULTS@#The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56-4.52, P 12 h) (OR 3.31, 95% CI 1.83-6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27-0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals.@*CONCLUSIONS@#Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.

Trends in mortality of emergency departments patients in China / 世界急诊医学杂志（英文）

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.

Current status and prospects of the survey of cardiac arrest and resuscitation / 中国实用内科杂志

Cardiac arrest(CA)is a common serious clinical event. The high incidence and low survival rate make it one of the important public health problems in China. We urgently need to investigate the incidence, mortality and risk factors of cardiac arrest in Chinese population. Based on epidemiological data on cardiac arrest in China, early identification of cardiac arrest and early initiation of cardiopulmonary resuscitation can significantly improve outcomes of patients with in-hospital and out-of-hospital cardiac arrest. The article summarizes the definition of cardiac arrest, the epidemiology, domestic and international gap and prospects of cardiac arrest in and out of hospital.

Mitochondrial aldehyde dehydrogenase in myocardial ischemia-reperfusion injury: from bench to bedside / 生理学报

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.

Roles of monocyte chemoattractant protein-1, RANTES and Fractalkine on promoting vulnerability of atherosclerotic plaques / 中华心血管病杂志

<p><b>OBJECTIVE</b>To elucidate the roles of monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) on the vulnerability of atherosclerotic plaques in patients with stable (SAP) and unstable angina pectoris (UAP).</p><p><b>METHODS</b>Patients with SAP (n = 50) and UAP (n = 50) underwent coronary angiography (CAG) and intravenous ultrasound (IVUS) were included in the study. Monocyte chemotaxis was assayed by the transwell chamber. Concentrations of hs-CRP, MCP-1, RANTES and Fractalkine were measured by Enzyme-linked-immunosorbent assay (ELISA). mRNA expression of MCP-1, RANTES and Fractalkine in the monocytes was detected by RT-PCR.</p><p><b>RESULTS</b>IVUS evidenced soft lipid plaques in 48% UAP patients and in 16% SAP patients (P < 0.05). SAP patients had mainly fibrous and mixed plaques. Plaque burden and vascular remodeling index were significantly higher in UAP patients than in SAP patients (P < 0.01). The averaged number of migrated monocytes in the UAP patients were higher than that in patients with SAP (P < 0.01). Concentration of hs-CRP, MCP-1, RANTES and Fractalkine were significantly higher in UAP patients than those of SAP patients (P < 0.05 or P < 0.01). mRNA expression of MCP-1, RANTES and Fractalkine in patients with UAP was significantly higher than those of SAP patients (P < 0.05).</p><p><b>CONCLUSION</b>Upregulated monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) might promote coronary plaque vulnerability in UAP patients.</p>

Reliability of transthoracic echocardiography in estimating the size of Amplatzer septal occluder and guiding percutaneous closure of atrial septal defects / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In China, transthoracic echocardiography (TTE) is popularly used for pre-intervention examination for atrial septal defect (ASD) and for guiding ASD closure. However, the ability to determine ASD size and the safety and efficacy of TTE for guiding ASD closure still has not been widely accepted. This study aimed to evaluate the efficacy and safety of TTE used before, during and after transcatheter ASD closure with Amplatzer septal occluders (ASO).</p><p><b>METHODS</b>Sixty-eight subjects (15 men and 53 women; mean age (33.7 +/- 17.3) years) were enrolled. TTE was used to measure the diameters and guide transcatheter closure of ASD. The ASD was examined by long-axis view, basal short-axis view, apical four-chamber view and the subcostal view to observe position, diameter and relation with neighbouring structures. The largest diameter was selected as the reference diameter. Patients were divided into 3 groups according to the ASD reference diameter: 22 subjects with ASD diameter 4 - 14 mm (group A); 21 subjects with ASD diameter 15 - 20 mm (group B); and 25 subjects with ASD diameter 21 - 33 mm (group C).</p><p><b>RESULTS</b>ASD was occluded successfully in groups A and B. In group C, occlusion failed in 2 cases; 1 case remained with a 3-mm residual shunt sustained until 6-month follow-up. However, at 6-month follow-up, no case of thromboembolism, ASO dislocation or death occurred in the three groups. The diameter of ASD measured by TTE could accurately predict the ASO size that could successfully occlude the ASD, especially in patients with ASD < 20 mm. The ASD diameter measured by TTE correlated well with ASO size (r = 0.925, P < 0.001; r = 0.976, P < 0.001; r = 0.929, P < 0.001 respectively).</p><p><b>CONCLUSIONS</b>ASD diameter measured by TTE can accurately estimate the size of the ASO needed for successful closure of ASD. The larger the ASD, the much larger the ASO needed. TTE is a satisfactory guiding imaging tool for ASD closure.</p>

Protective effect of luomaishutong on acute myocardial ischemia reperfusion injury in rabbits / 中华急诊医学杂志

Objective To evaluate the protective effect and mechanism of luomaishutong(LMST)on acute myocardial ischemia-reperfusion injury in rabbits.Method Twenty-four New Zealand white rabbits were randomly divided into 3 groups:the LMST group,the control group and the sham-operated group.The AMI reperfusion model was established by removing the blockade after the occlusion of coronary artery for 2 hours.The changes of hemodynamics,oxygen free radical and clearance system were measured in all rabbits.Results (1)Compared with the control group,left ventricular systolic pressure(LVSP)and maximal changing rate of left ventricular innner pressure(?dp/dt_(max))increased remarkably in the LMST group after reperfusion,meanwhile, LVEDP decreased significantly.(2)In the control group,MDA level of cardiocyte was noticeably higher,while SOD and NOS levels were lower than in the sham-operated group.Compared with the control group,MDA level in the LMST group was significantly lower.Furthermore,SOD and NOS levels were higher in LMST group,and the infarcted area was smaller in the LMST group as well.Conclusions LMSF can protect myocardium after ischemia-repcrfusioninjury and improve cardiac function through inhibiting induced by oxygen free radicals.

Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS).</p><p><b>METHODS</b>One hundred and fifteen patients with NSTEACS were randomized into two groups: group A (aspirin alone, n =58) and group B (aspirin plus clopidogrel, n =57). Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls (group C).</p><p><b>RESULTS</b>Baseline levels of hs-CRP and TNF-alpha in group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A: (6.15 +/- 1.39) mg/L vs (9.18 +/- 1.62) mg/L, P <0.01; Group B:(4.99 +/- 1.62) mg/L vs (10.29 +/- 1.47) mg/L, P <0.01]. Similarly, levels of TNF- alpha in both groups decreased at 7 days compared to baseline [Group A: (90.99 +/- 28.91) pg/ml vs (117.20 +/- 37.13) pg/ml, P <0.01; Group B: (74.32 +/- 21.83) pg/ml vs (115.27 +/- 32.11) pg/ml, P <0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to (3.49 +/- 1.53) mg/L, and (2.40 +/- 1.17) mg/L respectively (P <0.01 for both comparisons). Levels of TNF-alpha in groups A and B also decreased significantly between 7 and 30 days, to 63.28 +/- 29.01 pg/ml (group A) and (43.95 +/- 17.10) pg/ml (group B; P <0.01 for both comparisons). Significantly lower levels of hs-CRP and TNF-alpha were observed in group B compared to Group A at thirty days after initiating drug treatment (P <0.05).</p><p><b>CONCLUSIONS</b>Aspirin plus clopidogrel treatment reduced levels of serum hs-CRP and TNF-alpha in patients with NSTEACS significantly more than aspirin alone. Because both aspirin and clopidogrel produce important anti-inflammatory effects, these results suggest the possibility that long-term treatment with aspirin plus clopidogrel may produce greater clinical benefits compared to treatment with aspirin alone.</p>

The role of atherosclerotic plaque stability and inflammation in the pathogenesis of acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To elucidate the effect of inflammation and coronary atherosclerotic plaque destabilization in the pathogenesis of acute coronary syndromes (ACS).</p><p><b>METHODS</b>Twenty-eight patients with ACS and 13 patients with stable angina pectoris (SA) were examined by intravascular ultrasound (IVUS). Coronary plaque morphology and areas in culprit lesions were analyzed. The serum levels of hs-CRP, MMP-9, TIMP-1, sCD40L were also measured.</p><p><b>RESULTS</b>Soft plaques were dominant in culprit lesions of ACS patients (71.4%, 20/28), and hard plaques were dominant in culprit lesions of SA patients [76.9% (10/13), P = 0.004]. At the culprit site, plaque area, plaque burden and remodeling index were all significantly larger in culprit lesions of ACS patients than those of SA patients (all P < 0.05). Positive remodeling was more frequent in ACS patients than in SA patients, whereas negative remodeling was more frequent in SA patients (P < 0.05). The serum levels of hs-CRP, MMP-9, sCD40L were higher in ACS group compared with SA group (P < 0.05, respectively). Moreover, hs-CRP level was positively correlated with MMP-9 (r = 0.671, P = 0.000) and sCD40L (r = 0.494, P = 0.008), respectively, in ACS patients. There was no difference in TIMP-1 between two groups (P = 0.234).</p><p><b>CONCLUSIONS</b>These results suggest that structurally vulnerable plaques are essential element in the pathogenesis of ACS and inflammation might play an important role in plaque vulnerability.</p>

Changes of neutrophil myeloperoxidase in coronary circulation among patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the changes of neutrophil myeloperoxidase (MPO) blood concentration gradient between the systemic circulation and the coronary circulation among patients with acute coronary syndrome and its clinical value.</p><p><b>METHODS</b>Fifty patients underwent coronary angiography, which including 10 patients in AMI group, 20 patients in UA group, 10 patients in SA group and 10 subjects served as control. The levels of MPO and hs-CRP were measured in the serum of blood collected from femoral vein, aortic artery root and coronary sinus.</p><p><b>RESULTS</b>Compared with the control, concentrations of LDL in the AMI, UA and SA groups were significantly increased, while the latter three groups did not differ from each other. In the UA patients, the in-gate percentage of MPO decreased in the coronary sinus compared with that in the root of aortic artery (P < 0.01); the in-gate percentage of MPO decreased through coronary circulation more than through systemic circulation (P < 0.001); the average fluorescent intensity of MPO and the concentrations of hs-CRP showed no difference between samples from the coronary sinus and that from the root of aortic artery. In the AMI patients, the average fluorescent intensity of MPO in the coronary sinus was weakened compared with that in the root of aortic artery (P < 0.05); it decreased through coronary circulation more than through systemic circulation (P < 0.001); neither the in-gate percentage of MPO nor the concentrations of hs-CRP showed significant difference between samples from the coronary sinus and that from the root of aortic artery. In the control and SA groups, samples from the femoral vein, the root of aortic artery, and the coronary sinus did not show differences at the serum level of MPO and hs-CRP. In the UA group, the in-gate percentage of MPO correlated positively with the concentration of hs-CRP (r = 0.78, P < 0.01), and with the level of LDL as well (r = 0.52, P < 0.05); In the AMI group, the average fluorescent intensity of MPO correlated negatively with the concentration of hs-CRP (r = -0.80, P < 0.01), and showed no correlation with the level of LDL (r = 0.22, P > 0.05).</p><p><b>CONCLUSIONS</b>MPO is a better marker for inflammation of the local plaques. It may be one of the mechanisms that MPO induces the transforming from LDL to ox-LDL in plaques vulnerability.</p>

Safety and immunogenicity of Bilive combined hepatitis A and B vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the safety and immunogenicity of the Bilive combined hepatitis A and B vaccine produced by Sinovac Biotech Co., Ltd.</p><p><b>METHODS</b>Samples were selected from first year students of a senior high school (adults group) and first to fifth grade 1-5 students of 3 primary schools (children group). Those who were susceptible to both hepatitis A virus (HAV) and hepatitis B virus (HBV), HAV only or HBV only were assigned to group AB, A and B respectively and were vaccinated with three doses (0, 1 and 6 month schedule) of Bilive combined hepatitis A and B vaccine, inactivated hepatitis A vaccine and recombined hepatitis B vaccine respectively. The dosage for adult group was 500 U hepatitis A antigen and/or 10 micro g hepatitis B surface antigen and the dosage for children group was half the dosage of adult group. The potential adverse effects were observed within 72 hours after vaccination. Serum samples were collected for testing anti-HAV and anti-HBs at month 2 and 7 after the initial dose.</p><p><b>RESULTS</b>The rates of local adverse effects were 0.58% and 2.56% in children AB group and adults AB group and the general adverse effects rates were 9.88% and 5.45% respectively. Both local and general adverse effect rates were not significantly different to the control group. The sero-conversion rate of anti-HAV in children and adults AB group reached 100%, one month after 3 doses. The geometric mean titer (GMTs) reached 33,910 mIU/ml and 23,435 mIU/ml respectively, significant higher than that in control group (group A). The sero-conversion rates of anti-HBs were 97.30% and 96.63%, and GMTs were 103 mIU/ml and 102 mIU/ml in children and adults AB group respectively. No significant difference on sero-conversion and GMT was observed when compared with control group.</p><p><b>CONCLUSION</b>The Bilive combined hepatitis A and B vaccine had good safety profile, and the immunogenicity both on anti-HAV and anti-HBs was similar to that of separated components.</p>