Long-term outcomes and independent predictors of mortality in patients presenting to emergency departments with acute heart failure in Beijing: a multicenter cohort study with a 5-year follow-up.

BACKGROUND: Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors. METHODS: This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors. RESULTS: The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023-1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958-0.983), fatigue (HR: 1.127, 95% CI: 1.009-1.258), ascites (HR: 1.190, 95% CI: 1.057-1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140-1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291-1.769), heart rate (HR: 1.003, 95% CI: 1.001-1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993-0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008-1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220-1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223-1.690), serum sodium (HR: 0.980, 95% CI: 0.972-0.988), serum albumin (HR: 0.981, 95% CI: 0.971-0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073-1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183-1.614), diabetes (HR: 1.118, 95% CI: 1.010-1.237), stroke (HR: 1.252, 95% CI: 1.121-1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626-0.814), ß-blockers (HR: 0.673, 95% CI: 0.588-0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604-0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646-0.965), spironolactone (HR: 0.814, 95% CI: 0.663-0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531-0.733), nitrates (HR: 0.715, 95% CI: 0.631-0.811), and digoxin (HR: 0.579, 95% CI: 0.465-0.721). CONCLUSIONS: The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, ß-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.

Association between anemia and outcome in patients hospitalized for acute heart failure syndromes: findings from Beijing Acute Heart Failure Registry (Beijing AHF Registry).

Whether the anemia increases the risk of mortality in patients with acute heart failure (AHF) remains unclear. This study aims to explore the relationship between anemia and outcomes in patients with AHF including subgroup analysis. This study included 3279 patients with hemoglobin available from the Beijing Acute Heart Failure Registry (Beijing AHF Registry) study. The primary endpoint was all-cause mortality in 1 year, and the secondary endpoint was 1-year all-cause events including all-cause death and readmission. Logistic regression models were applied to describe related variables of anemia in patients with AHF. Multivariate Cox proportional hazards models described associations of anemia with clinical outcomes in the overall cohort and subgroups. 45.4% of the patients were found anemic. They were older and had more comorbidities than non-anemic patients. Variables including older age, female, chronic kidney dysfunction (CKD), lower hematocrit, lower albumin, with loop diuretics applied, without beta-blockers, angiotensin-converting enzyme inhibitors /angiotensin receptor blockers (ACEIs/ARBs) and spironolactone applied in the emergency department (ED) were associated with anemia in AHF patients. Anemic patients had higher 1-year mortality (38.4% vs. 27.2%, p < 0.0001) and 1-year events rates (63.2% vs. 56.7%, p < 0.0001). After adjusted for covariates, anemia was associated with the increase of 1-year mortality (hazard ratio [HR] 1.278; 95% confidence interval [CI] 1.114-1.465; p = 0.0005) and 1-year events (HR 1.136; 95% CI 1.025-1.259; p = 0.0154). The severer anemia patients had higher risks both of 1-year mortality and events. In the subgroup analysis, the independent associations of anemia with 1-year mortality were shown in the subgroups including age < 75 years, male, body mass index < 25 kg/m2 and BMI ≥ 25 kg/m2, New York Heart Association (NYHA) functional class I-II and NYHA functional class III-IV, with and without cardiovascular ischemia, heart rate (HR) < 100 bpm and HR ≥ 100 bpm, systolic blood pressure (SBP) < 120 mmHg and SBP ≥ 120 mmHg, left ventricular ejection fraction (LVEF) < 40% and LVEF ≥ 40%, serum creatinine (Scr) < 133 umol/l, and with diuretics use, with and without beta-blockers use, without ACEIs/ARBs use in the ED. Anemia is associated with older age, female, CKD, volume overload, malnutrition, with loop diuretics, without beta-blockers, ACEIs/ARBs and spironolactone administration, and higher mortality and readmission in AHF. The risk associations are particular significantly obvious in younger, male, overweight, preserved LVEF, lower Scr, with diuretics and beta-blockers, without ACEIs/ARBs administration subgroups.Clinical trial No. ChiCTR-RIC-17014222.

Human umbilical cord mesenchymal stem cells derived exosomes exert antiapoptosis effect via activating PI3K/Akt/mTOR pathway on H9C2 cells.

BACKGROUND/OBJECTIVES: In recent years, as an alternative to stem cell therapy for cardiovascular diseases (CVD), exsomes have attracted wide attention among researchers. The present study aimed to investigate the role of human umbilical cord mesenchymal stem cells (UC-MSCs) derived exosomes play on H9C2 cells apoptosis and possible mechanisms. METHODS: Exosomes were isolated from normal UC-MSCs culture media and hypoxic preconditioning culture media. Transmission electron microscopy was used to observe the morphology of exosomes. Nanoparticle tracking analysis was used to detect the size distribution and concentration of exosomes. Western blot analysis was used to analyzed the surface marker CD63 of exosomes. H9C2 cells were induced apoptosis by hypoxia and serum deprivation (H/SD) and then were treated respectively by group. Cell Counting Kit-8 assay was used to detect viability of H9C2 cells. Apoptosis was detected by Hochest staining and annexin V-FITC/PI. The expression levels of related proteins of apoptosis, autophagy, and PI3K/Akt/mTOR pathway were analyzed by Western blot analysis. Immunofluorescence was used to analyze LC3B expression. RESULTS: Hypoxic preconditioning increased the exosomes secretion of UC-MSCs. UC-MSCs derived exosomes could inhibit H/SD-induced H9C2 cells apoptosis. Hypoxic preconditioning strengthened this antiapoptosis effect of UC-MSCs. Hypoxic preconditioning UC-MSCs derived exosomes (H-Exo) downregulated LC3B-II/I and beclin-1 and upregulated P62, p-Akt/Akt and p-mTOR/mTOR. The antiapoptotic effect of H-Exo could be attenuated by treatment with LY294002 and rapamycin. CONCLUSION: UC-MSCs derived exosomes could inhibit H9C2 cells apoptosis induced by H/SD through regulating autophagy via PI3K/Akt/mTOR pathway. Hypoxia preconditioning could enhance above effects through increasing exosomes secretion of UC-MSCs.

Exosomes derived from SDF1-overexpressing mesenchymal stem cells inhibit ischemic myocardial cell apoptosis and promote cardiac endothelial microvascular regeneration in mice with myocardial infarction.

Exosomes extracted from mesenchymal stem cells (MSCs) was reported to reduce myocardial ischemia/reperfusion damage. Besides, stromal-derived factor 1 (SDF1a) functions as cardiac repair after myocardial infarction (MI). Therefore, the present study aims to identify whether exosomes (Exo) released from SDF1-overexpressing MSCs display a beneficial effect on ischemic myocardial infarction. Initially, a gain-of-function study was performed to investigate the function of SDF1 in ischemic myocardial cells and cardiac endothelial cells. Coculture experiments were performed to measure potential exosomic transfer of SDF1 from MSCs to ischemic myocardial cells and cardiac endothelial cells. During the coculture experiments, exosome secretion was disrupted by neutral sphingomyelinase inhibitor GW4869 and upregulated exosomal SDF1 using SDF1 plasmid. Effects of Exo-SDF1 on cardiac function in MI mice were investigated in vivo. MSCs suppressed myocardial cell apoptosis and promoted microvascular regeneration of endothelial cells through secretion of exosomes. The addition of GW4869 led to increased apoptotic capacity of myocardial cells, decreased microvascular formation ability of endothelial cells, enhanced autophagy ability, and elevated Beclin-1 level as well as ratio of LC3II/LC3I. Overexpression of SDF1 and Exo-SDF1 inhibited apoptosis and autophagy of myocardial cells, but promoted tube formation of endothelial cells. The interference of PI3K signaling pathway promoted apoptosis and autophagy of myocardial cells, but inhibited tube formation of endothelial cells. SDF1 activated the PI3K signaling pathway. Exo-SDF1 protected cardiac function of MI mice and inhibited myocardial tissue damage. This study provided evidence that SDF1 overexpression in MSCs-derived exosomes inhibited autophagy of ischemic myocardial cells and promoted microvascular production of endothelial cells.

Characteristics, Management, and Outcomes of Acute Heart Failure in the Emergency Department: A Multicenter Registry Study with 1-year Follow-up in a Chinese Cohort in Beijing.

BACKGROUND: The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF. METHODS: This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables. RESULTS: The median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively. CONCLUSIONS: Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.

Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ±â€Š5.95 vs -1.82 ±â€Š4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

Cerebral infarction caused by a heart-breaking needle: a case report.

BACKGROUND: In this report, we describe a case of cerebral infarction caused by cardiac foreign body-induced infective endocarditis. We discuss the paradox of the treatment we used and highlight the need for careful examination of patients without histories and complaints of cardiac disease. CASE PRESENTATION: Our patient was a 48-year-old Asian woman who presented with symptoms of cerebral infarction without any characteristic features of infective endocarditis. Appropriate treatment had been delayed, which made her therapy a little bit complicated. The optimal treatment of our patient was apparently surgery. However, the appropriate timing of her operation is still argued among surgeons at our department because of her acute cerebral infarction. CONCLUSIONS: Patients with cardiac foreign bodies need timely surgery, especially patients who display symptoms of nervous system or cardiovascular system imbalance. In this case report, we share our experiences with treating such a patient, which may have some clinical implications in a contradictory situation. To the best of our knowledge, this report is the first of its kind and will broaden understanding of the clinical diagnosis of this type of case.

Human umbilical cord blood derived mesenchymal stem cells improve cardiac function in cTnT(R141W) transgenic mouse of dilated cardiomyopathy.

Cell transplantation is a promising strategy in regenerative medicine. Beneficial effects of bone marrow mesenchymal stem cells (BM-MSCs) on heart disease have been widely reported. However, the MSCs in these studies have been mainly derived from autologous animals, and data on MSCs from human umbilical cord blood (UCB-MSCs) are still scarce. We investigated whether intramyocardial xenogeneic administration of UCB-MSCs is beneficial for preserving heart function in a cTnT(R141W) transgenic mouse of dilated cardiomyopathy (DCM). Cultured UCB-MSCs, which were identified by there morphology, differentiation and cell surface markers, were transplanted into cTnT(R141W) transgenic mice to examine apoptosis, fibrosis, vasculogenesis and the associated Akt pathway. Moreover, we measured the expression levels of VEGF and IGF-1, which are growth factors required for differentiation into cardiomyocytes, and are also involved in cardiac regeneration and improving heart function. One month after transplantation, MSCs significantly decreased chamber dilation and contractile dysfunction in the cTnT(R141W) mice. MSCs transplanted hearts showed a significant decrease in cardiac apoptosis and its regulation by the Akt pathway. Cardiac fibrosis and cytoplasmic vacuolisation were significantly attenuated in the MSCs group. Importantly, the levels of VEGF and IGF-1 were increased in the MSCs transplanted hearts. In vitro, the MSC-conditioned medium displayed anti-apoptotic activity in h9c2 cardiomyocytes subjected to hypoxia. These results further confirm the paracrine effects of MSCs. In conclusion, UCB-MSCs preserve cardiac function after intramyocardial transplantation in a DCM mouse, and this effect may be associated with reductions in cellular apoptosis, inflammation, hypertrophy and myocardial fibrosis; in addition to; up-regulation of Akt, VEGF and IGF-1; and enhanced angiogenesis.

Trimetazidine protects umbilical cord mesenchymal stem cells against hypoxia and serum deprivation induced apoptosis by activation of Akt.

BACKGROUND: Mesenchymal stem cell (MSC) transplantation is a promising therapy for cardiac repair. However, the efficacy is limited by the poor viability of MSCs in the infarcted heart. Recent findings have implicated that trimetazidine (TMZ) enhanced the survival of the stem cells under various conditions. However, as the stem cells in these studies were animal-derived, little information is available about the effects of TMZ on human MSCs. Herein, we propose that TMZ may protect human MSCs against apoptosis induced by Hypoxia/Serum deprivation (H/SD). METHODS: Human umbilical cord MSCs (UC-MSCs) from Wharton's jelly were pretreated with 10µM TMZ of H/SD with or without the Akt inhibitor LY294002. The morphological changes were assessed using Hoechst 33342. Apoptosis was evaluated via Annexin V/PI staining; and apoptosis-related proteins were detected using Western-blot. Protein chip technology was used to screen for differences between the cell supernatants. RESULTS: TMZ had a significant protective effect against H/SD-induced apoptosis, accompanied by an increase in Bcl-2 and p-Akt. The TMZ-mediated anti-apoptotic effect on MSCs could be attenuated by treatment with LY294002. Moreover, protein chip assays showed that TMZ treatment increased the paracrine functions of MSCs. CONCLUSION: Trimetazidine protects human UC-MSCs from H/SD-induced apoptosis via the Akt pathway and may therefore be a potentially useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction.

[Short-term prognosis and risk factors of ventricular septal rupture following acute myocardial infarction].

OBJECTIVE: To analyze the short-term prognosis and risk factors of ventricular septal rupture (VSR) following acute myocardial infarction (AMI). METHODS: A total of 70 consecutive VSR patients following AMI hospitalized in our hospital from January 2002 to October 2010 were enrolled in this study. We compared the clinical characteristics of patients with VSR who survived ≤ 30 days (n = 39) and survived > 30 days (n = 31) post AMI. A short-term prognosis index of VSR (SPIV) was established based on the logistic regression analysis. RESULTS: The single factor analysis showed that the risk factors of death within 30 days of VSR patients were female, anterior AMI, Killip class 3 or 4, apical VSR and non-aneurysm (all P < 0.05). Logistic regression analysis revealed that female (P = 0.013), anterior AMI (P = 0.023), non-aneurysm (P = 0.023), non-diabetes (P = 0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days (P = 0.027) were independent risk determinants for death within 30 days post VSR. Patients with SPIV ≥ 9 were associated with high risk [77.4% (24/31)] of dying within 30 days post AMI. SPIV ≤ 8 were associated with low risk as the 30 days mortality is 28.6% (8/28). CONCLUSION: Female gender, anterior AMI, non-aneurysm, non-diabetes, Killip class 3 or 4 and time from AMI to VSR less than 4 days are independent risk factors of short-term mortality of VSR.

[Clinical characteristics of 22 cases of fungal infective endocarditis].

OBJECTIVE: To explore the clinical characteristics, treatment regimens and outcomes of the patients with fungal infective endocarditis. METHODS: An observational study was conducted at our hospital and recruited 22 consecutive patients with a definite diagnosis of fungal infective endocarditis. Their overall characteristics, treatments, complications and outcomes were analyzed. RESULTS: The mean age at presentation was 45 years with a slight male preponderance. Among them, 13 cases had healthcare-associated infective endocarditis and 1 patient was an intravenous drug user. Aortic valve (40.9%) was most commonly affected and it was followed by mitral valve (13.6%). The most common etiological agent was Candida (68.2%), followed by Aspergillus (22.7%). Risk factors include the prosthetic valve replacement surgery, impaired immune function, and so on. Major complications during the acute infective phase were also recorded, including heart failure, embolic events, uncontrolled infections and renal dysfunction. The overall hospital mortality rate was 40.9%. There were 15 patients with antifungal treatment, which including fluconazole, itraconazole, caspofungin acetate and voriconazole itraconazole. The remaining 7 patients (31.8%) underwent valve replacement surgery, including 3 cases of cardiac valve re-replacement. A better outcome was observed in patients on a combined regimen of medical and surgical therapies. CONCLUSIONS: Fungal endocarditis is associated with more invasive interventions and immunocompromised patients. The incidence of embolic events and in-hospital mortality is still high in patients with fungal endocarditis, and the larger vegetation is more common. Heart failure, sepsis and repeated arterial embolization are the most common cause of death.

Comparison of characteristics and short-term outcome from fungal infective endocarditis in prosthetic valve endocarditis versus native valve endocarditis.

Fungal infective endocarditis (IE) is a rare, serious, and potentially lethal disease, yet its clinical characteristics and short-term outcomes remain poorly understood. A detailed comparative analysis of fungal prosthetic valve endocarditis (PVE) and native valve endocarditis (NVE) has not been performed. This study was designed to explore the general characteristics, treatment patterns, and outcomes of patients with fungal IE in a Chinese hospital and compare these data between PVE and NVE. Four hundred ninety-three patients were admitted to Fuwai hospital from January 2002 to December 2010. Fungal IE accounted for 7% (32 cases) of cases. Of these patients, 19 (59%) patients had NVE, 12 (37%) PVE, and 1 (3%) cardiac device-related infective endocarditis (CDRIE). Candida albicans remained the predominant causative pathogen (47% of all IE). Patients with NVE, compared with PVE patients, were older (50 years vs 37 years, p = 0.034), had less frequent history of previous endocarditis (0 vs 25%, p = 0.049), and were more likely to have a history of diabetes (37% vs 0, p = 0.026) and be in an immunocompromised state (37% vs 0, p = 0.026). Nearly half of the patients died of refractory heart failure, followed by severe sepsis and stroke. In-hospital mortality rate was 38%, and the 3-month cumulative mortality rate was 47%. Recurrence of IE was more common in fungal PVE patients (42% vs 5%, p = 0.022) during the 90-day follow-up. In conclusion, fungal IE is associated with high mortality and recurrence rates. Surgery performed in selected cases may improve the outcomes, but the recurrence rate remains high.

Telmisartan, ramipril, or both in high-risk Chinese patients: analysis of ONTARGET China data.

BACKGROUND: The results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China. METHODS: A total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years. RESULTS: The mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1.6% and 1.0%). CONCLUSIONS: There was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

[Influencing factors for the plasma concentration of N-terminal brain natriuretic peptide precursor in patients with heart failure due to various heart diseases].

OBJECTIVE: To compare the plasma concentrations of N-terminal brain natriuretic peptide precursor (NT-proBNP) in patients with heart failure due to various heart diseases and analyze the influencing factors. METHODS: We enrolled a total of 804 heart failure patients due to various heart diseases, including valvular heart disease (VHD), dilated cardiomyopathy (DCM), ischemic heart diseases (IHD), restrictive cardiomyopathy (RCM), hypertensive heart disease (HHD), hypertrophic cardiomyopathy (HCM), pulmonary heart disease (PHD) and adult congenital heart disease (CHD). The plasma concentration of NT-proBNP was measured by enzyme-linked immunosorbent assay (ELISA). Multiple linear regression analysis was used to detect the influencing factors for the plasma concentration of NT-proBNP. RESULTS: The plasma concentration of NT-proBNP had no significant difference between patients with VHD, DCM, IHD, RCM, HCM, PHD, HHD and CHD. The median (25 percent, 75 percent) values were 1866 (803 - 3973), 2247 (1087 - 3865), 2400 (1182 - 4242), 2456 (1385 - 5839), 2204 (1053 - 3186), 2285 (1155 - 3424), 2313 (655 - 3850) and 2768 (795 - 4371) pmol/L respectively (P > 0.05). It increased with New York Heart Association (NYHA) class from II through III to IV. The median (25 percent, 75 percent) values were 646 (447 - 1015), 2160 (1118 - 3750) and 3342 (1549 - 5455) pmol/L respectively (P < 0.01). The patients with a body mass index (BMI) of ≥ 25 kg/cm(2) had a lower NT-proBNP concentration than those with a BMI of < 25 kg/cm(2). The median (25 percent, 75 percent) values were 1468 (784 - 3177) and 2424 (1090 - 4213) pmol/L respectively (P < 0.01). Patients with a serum creatinine concentration of ≥ 107 µmol/L had a higher NT-proBNP concentration than those < 107 µmol/L. The median (25 percent, 75 percent) values were 3337 (1470 - 5380) and 1644 (781 - 3375) pmol/L respectively (P < 0.01). Multiple linear regression analysis demonstrated that NYHA class, creatinine, BMI, hepatic damage and diastolic pressure were independently associated with the plasma concentration of NT-proBNP (all P < 0.01). CONCLUSION: The plasma concentration of NT-proBNP has no significant difference between heart failure patients due to various heart diseases. Its level may be affected by NYHA class, serum creatinine, BMI, hepatic damage and diastolic pressure.

Atorvastatin attenuates Coxsackie virus B3m-induced viral myocarditis in mice.

In the present study, we determined the therapeutic efficacy of atorvastatin on Coxsackievirus B3m (CVB3m)-induced myocarditis. Mice were administered Eagle minimal essential medium, virus solution, atorvastatin, or virus plus atorvastatin. Atorvastatin was given 3 days after viral challenge, and the treatment lasted for 14 days. On days 3, 7, 10, 14, 21, and 30 after virus inoculation (same days for the atorvastatin only group), echocardiograms were performed, and blood samples were collected for cardiac troponin I analysis. Myocardial inflammation, cell apoptosis, and Fas expression were detected by histology and immunohistochemistry. Hematoxylin and eosin staining and transmission electron microscopy revealed significant improvement of quantitative pathological features in the CVB3m-infected group treated with atorvastatin. Immunohistochemistry also showed a marked decrease in apoptosis of cardiac cells in the atorvastatin-treated group compared with infected animals without treatment. The differences in the values of cardiac troponin I between the atorvastatin treated and untreated virus-challenged mice were statistically significant (P < 0.05). Reverse transcription-polymerase chain reaction and western blotting revealed that the virus induced marked increases in Fas messenger RNA and protein expression, which was reversed by atorvastatin. These results demonstrate that atorvastatin reduces the histological and functional severity of CVB3m-induced myocarditis and inhibits apoptosis and Fas expression in the myocardium of type B Coxsackie virus-infected mice.

[Value of admission NT-proBNP in predicting in-hospital mortality in decompensated systolic heart failure].

OBJECTIVE: To evaluate the value of NT-proBNP in predicting in-hospital mortality in patients with decompensated systolic heart failure. METHODS: Plasma NT-proBNP levels within 24 hours of admission were obtained in 366 patients with decompensated systolic heart failure. The levels were compared between dying patients in hospital and survival patients at discharge. ROC analyses were performed to evaluate if NT-proBNP was a predictor for in-hospital mortality and identify the optimal NT-proBNP cut-off point for predicting in-hospital mortality. A binary logistic regression analysis was used to evaluate if NT-proBNP was an independent predictor for in-hospital mortality. RESULTS: 19 cases of the 366 patients died in hospital. NT-proBNP levels of the dying cases were much higher than those of the survivals 3970 (3452, 6934) pmol/L vs 2340 (1132, 4002) pmol/L respectively, P < 0.01). ROC analysis of NT-proBNP to predict in-hospital mortality had an area under the curve (AUC) of 0.762 (95% CI: 0.657-0.857, P < 0.01), the optimal NT-proBNP cut-off point for predicting in-hospital mortality was 3500 pmol/L with a sensitivity of 73.7%, a specificity of 66.9%, an accuracy of 67.6% and a negative predictive value of 97.9%. Patients whose NT-proBNP levels were equal or more than 3500 pmol/L had an in-hospital mortality of 10.9%, compare with 2.1% in those NT-proBNP levels less than 3500 pmol/L (P < 0.01). Binary logistic regression analysis demonstrated that NT-proBNP was an independent predictor for in-hospital mortality in patients with decompensated systolic heart failure (P < 0.01). CONCLUSION: Admission plasma NT-proBNP level is an independent predictor for in-hospital mortality in patients with decompensated systolic heart failure. The optimal NT-proBNP cut-off point for predicting in-hospital mortality is 3500 pmol/L.

[Clinical characteristic analysis of the first human case infected by influenza A (H5N1) in Jiangxi Province].

OBJECTIVE: To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis. METHODS: The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed. RESULTS: The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed. CONCLUSION: The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.

Herpes simplex virus type 2 infection is a risk factor for hypertension.

Herpes simplex virus type 2 (HSV-2), which has been recognized as a potential cardiovascular pathogen and implicated in carotid atherosclerosis and coronary artery disease, is independently associated with the future risk of cardiovascular death. Investigations have demonstrated that hypertension may be related to inflammation, and inflammation is one of the symptoms of HSV-2 infection. This cross-sectional study investigated the correlation between HSV-2 infection and essential hypertension. One thousand two hundred and forty four inpatients (488 patients with essential hypertension and 756 normotensives) were investigated serologically for the specific immunoglobulin G (IgG) to HSV-2 by enzyme-linked immunosorbent assay. Patients diagnosed with pheochromocytoma, primary aldosteronism, aorto-arteritis or renal artery stenosis were excluded. The prevalence of HSV-2 IgG seropositivity was significantly higher in the hypertensive group than in the normotensive group (38.3% vs. 29.8%, p =0.002). After adjustment for confounding factors, an association of HSV-2 IgG seropositivity with essential hypertension was found on binary logistic regression analysis. The adjusted odds ratio of essential hypertension was 1.4 (95% confidence intervals, 1.1 to 1.8; p =0.005) for HSV-2 infection; the adjusted covariates included age, male sex, smoking, body mass index, dyslipidemia, diabetes and coronary artery disease. The results of this study indicated that HSV-2 infection might be an independent risk factor for essential hypertension.

[Chlamydia pneumoniae infection increases the risk of coronary artery disease in the patients with dyslipidemia].

OBJECTIVE: To investigates the role of chlamydia pneumoniae (CP) infection in the development of coronary artery disease (CAD) in the patients with dyslipidemia, and to examine the gender related differences in this role. METHODS: 523 inpatients with dyslipidemia and 1196 inpatients without dyslipidemia tested for specific CP IgG by enzyme-linked immunoassay. Multivariate analyses were performed in the patients with and without dyslipidemia, and in the subgroups of male and female dyslipidemic patients to get the adjusted odds ratio (OR) (95% confidence intervals) of CAD for a given risk factor. RESULTS: After adjusting for age over 55 years, male sex, smoking, hypertension and diabetes, the OR of CAD associated with CP infection was 2.5 (1.4 to 4.6, P = 0.002) in the patients with dyslipidemia, and was 0.967 (0.7 - 1.4, P = 0.851) in those without dyslipidemia. In comparison with the male patients with dyslipidemia, the adjusted OR of CAD was 2.1 (1.1 to 4.1) for CP infection and 3.3 (1.9 - 5.9) for smoking; only CP infection was significantly contributed to CAD in female dylipidemic patients, with an adjusted OR of 4.4 (1.4 to 14.6). CONCLUSION: CP infection increases the risk of CAD only in patients with dyslipidemia, and this increase was greater in women than in men.