A prediction model for left ventricular thrombus persistence/recurrence: based on a prospective study and a retrospective study.

BACKGROUND: It remains unknown whether anticoagulation for persistent left ventricular (LV) thrombus should be continued indefinitely. Identifying patients with a high risk of thrombus unresolved may be helpful to determine the optimum anticoagulation duration. This study aimed to develop a prediction model to forecast thrombus persistence or recurrence in patients with LV thrombus. METHODS: We enrolled patients prospectively from 2020 to 2022 and retrospectively from 2013 to 2019 at the National Center of Cardiovascular Diseases of China. The two cohorts were then combined to derive predictive models of thrombus persistence/recurrence. The primary study comprised patients who received systemic oral anticoagulants and had imaging records available at the end of a 3-month follow-up period. The Lasso regression algorithm and the logistic regression were performed to select independent predictors. The calibration curve was generated and a nomogram risk prediction model was applied as a risk stratification tool. RESULTS: A total of 172 (64 in the prospective cohort and 108 in the retrospective cohort) patients were included, with 124 patients in a training set and 48 patients in a validation set. Six predictors were incorporated into the multivariate logistic regression prediction model. The area under the receiving operating characteristic was 0.852 in the training set and 0.631 in the validation set. Patients with protuberant thrombus and higher baseline D-dimer levels had a reduced risk of persistence/recurrence (OR 0.17, 95% CI 0.03-0.69, P = 0.025; OR 0.67, 95% CI 0.43-0.91, P = 0.030, separately), whereas thicker thrombus was linked to an increased rate of persistent thrombus (OR 1.11, 95% CI 1.05-1.20, P = 0.002). Additionally, patients with diverse diagnoses or receiving different antiplatelet treatments had different rates of LV thrombus persistence/recurrence at 3 months. CONCLUSIONS: This prediction model provides tools to forecast the occurrence of persistent/recurrent thrombus and allows the identification of characteristics associated with unresolved thrombus. To validate the model and determine the duration of anticoagulation in patients with persistent thrombus, prospective randomized trials are necessary.

An exploratory study of effectiveness and safety of rivaroxaban in patients with left ventricular thrombus (R-DISSOLVE).

Evidence on the treatment for left ventricular (LV) thrombus is limited and mainly derives from retrospective studies. The aim of R-DISSOLVE was to explore the effectiveness and safety of rivaroxaban in patients with LV thrombus. R-DISSOLVE was a prospective, interventional, single-arm study, conducted from Oct 2020 to June 2022 at Fuwai Hospital, China. Patients with a history of LV thrombus < 3 months and with systemic anticoagulation therapy < 1 month were included. The thrombus was quantitatively confirmed by contrast-enhanced echocardiography (CE) at baseline and follow-up visits. Eligible patients were assigned to rivaroxaban (20 mg once daily or 15 mg if creatinine clearance was between 30 and 49 mL/min) and its concentration was determined by detecting anti-Xa activity. The primary efficacy outcome was the rate of LV thrombus resolution at 12 weeks. The main safety outcome was the composite of ISTH major and clinically relevant non-major bleeding. A total of 64 patients with complete CE results were analyzed for efficacy outcomes. The mean LV ejection fraction was 25.4 ± 9.0%. The dose-response curve of rivaroxaban was satisfactory based on the peak and trough plasma levels and all concentrations were in the recommended treatment range according to NOAC guidelines. The incidence rate of thrombus resolution at 6 weeks was 66.1% (41/62, 95% CI 53.0-77.7%), and of thrombus resolution or reduction was 95.2% (59/62, 95% CI 86.5-99.0%). At 12 weeks, the thrombus resolution rate was 78.1% (50/64, 95% CI 66.0-87.5%) while the rate of thrombus resolution or reduction was 95.3% (61/64, 95% CI 86.9-99.0%). The main safety outcome occurred in 4 of 75 patients (5.3%) (2 ISTH major bleeding and 2 clinically relevant non-major bleeding). In patients with LV thrombus, we reported a high thrombus resolution rate with acceptable safety by rivaroxaban, which could be a potential option for further LV thrombus treatment.Trial registration This study was registered at ClinicalTrials.gov as NCT04970381.

Sex-related prognostic value of systolic blood pressure on admission in critically ill patients with acute decompensated heart failure.

The present study aimed to evaluate sex-specific association between admission systolic blood pressure (SBP) and in-hospital prognosis in patients with acute decompensated heart failure (ADHF) admitted to intensive care unit (ICU). In this retrospective, observational study, 1268 ADHF patients requiring intensive care were consecutively enrolled and divided by sex. Patients were divided into three subgroups according to SBP tertiles: high (≥ 122 mmHg), moderate (104-121 mmHg) and low (< 104 mmHg). The primary endpoint was either all-cause mortality, cardiac arrest or utilization of mechanical support devices during hospitalization. Female patients were more likely to be older, have poorer renal function and higher ejection fractions (p < 0.001). The C statistics of SBP was 0.665 (95%CI 0.611-0.719, p < 0.001) for men and 0.548 (95% CI 0.461-0.634, p = 0.237) for women, respectively. Multivariate analysis demonstrated that admission SBP as either a continuous (OR = 0.984, 95% CI 0.973-0.996) or a categorical (low vs. high, OR = 3.293, 95% CI 1.610-6.732) variable was an independent predictor in male but the risk did not statistically differ between the moderate and high SBP strata (OR = 1.557, 95% CI 0.729-3.328). In female, neither low (OR = 1.135, 95% CI 0.328-3.924) nor moderate (OR = 0.989, 95% CI 0.277-3.531) SBP had a significant effect on primary endpoint compared with high SBP strata. No interaction was detected between left ventricular ejection fraction (LVEF) and SBP (p for interaction = 0.805). In ADHF patients admitted to ICU, SBP showed a sex-related prognostic effect on primary endpoint. In male, lower SBP was independently associated with an increased risk of primary endpoint. Conversely, in female, no relationship was observed.

A new scoring system for predicting short-term outcomes in Chinese patients with critically-ill acute decompensated heart failure.

BACKGROUND: Acute decompensated heart failure (ADHF) contributes millions of emergency department (ED) visits and it is associated with high in-hospital mortality. The aim of this study was to develop and validate a multiparametric score for critically-ill ADHF patients. METHODS: In this single-center, retrospective study, a total of 1268 ADHF patients in China were enrolled and divided into derivation (n = 1014) and validation (n = 254) cohorts. The primary endpoint was any in-hospital death, cardiac arrest or utilization of mechanical support devices. Logistic regression model was preformed to identify risk factors and build the new scoring system. The assigning point of each parameter was determined according to its ß coefficient. The discrimination was validated internally using C statistic and calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit test. RESULTS: We constructed a predictive score based on six significant risk factors [systolic blood pressure (SBP), white blood cell (WBC) count, hematocrit (HCT), total bilirubin (TBIL), estimated glomerular filtration rate (eGFR) and NT-proBNP]. This new model was computed as (1 × SBP < 90 mmHg) + (2 × WBC > 9.2 × 109/L) + (1 × HCT ≤ 0.407) + (2 × TBIL > 34.2 µmol/L) + (2 × eGFR < 15 ml/min/1.73 m2) + (1 × NTproBNP ≥ 10728.9 ng/ml). The C statistic for the new score was 0.758 (95% CI 0.667-0.838) higher than APACHE II, AHEAD and ADHERE score. It also demonstrated good calibration for detecting high-risk patients in the validation cohort (χ2 = 6.681, p = 0.463). CONCLUSIONS: The new score including SBP, WBC, HCT, TBIL, eGFR and NT-proBNP might be used to predict short-term prognosis of Chinese critically-ill ADHF patients.

Increased mortality in patients with secondary diagnosis of atrial fibrillation: Report from Chinese AF registry.

BACKGROUND: The relationship between mortality and the primary diagnosis in AF patients is poorly recognized. The purpose of the study is to compare the differences on mortality in patients with a primary or secondary diagnosis of AF and to identify risk factors amenable to treatment. METHODS: This was a prospective cohort study using data from the Chinese AF registry. For admitted patients, a follow-up was completed to obtain the outcomes during 1 year. RESULTS: A total of 2015 patients with confirmed AF were included. AF was the primary diagnosis in 40.9% (n = 825) of them. 78.9% (n = 939) of the secondary AF diagnosis patients and 55.5% (n = 458) of the primary AF diagnosis patients were sustained AF. Compared with primary AF diagnosis group, the secondary AF diagnosis group was older with more comorbidities. At 1 year, the unadjusted mortality was much higher in the secondary AF diagnosis groups compared with the primary AF diagnosis groups. In Cox regression analysis with adjustment for confounding factors, patients with secondary AF diagnosis were associated with an increased mortality (relative risk 1.723; 95% CI: 1.283 to 2.315, p < .001). On multivariate analysis, age ≥ 75, LVSD, COPD, and diabetes were independent predictors of mortality in patients with primary AF diagnosis, while for the secondary AF diagnosis group, the risk factors were age ≥ 75, heart failure, and previous history of stroke. CONCLUSIONS: Patients presenting to ED with secondary diagnosis of AF were suffering from higher mortality risks compared with primary AF diagnosis patients. Physicians should distinguish these two groups in clinical practice.

Clinical characteristics and prognosis of heart failure with mid-range ejection fraction: insights from a multi-centre registry study in China.

BACKGROUND: Heart failure (HF) with mid-range ejection fraction (EF) (HFmrEF) has attracted increasing attention in recent years. However, the understanding of HFmrEF remains limited, especially among Asian patients. Therefore, analysis of a Chinese HF registry was undertaken to explore the clinical characteristics and prognosis of HFmrEF. METHODS: A total of 755 HF patients from a multi-centre registry were classified into three groups based on EF measured by echocardiogram at recruitment: HF with reduced EF (HFrEF) (n = 211), HFmrEF (n = 201), and HF with preserved EF (HFpEF) (n = 343). Clinical data were carefully collected and analyzed at baseline. The primary endpoint was all-cause mortality and cardiovascular mortality while the secondary endpoints included hospitalization due to HF and major adverse cardiac events (MACE) during 1-year follow-up. Cox regression and Logistic regression were performed to identify the association between the three EF strata and 1-year outcomes. RESULTS: The prevalence of HFmrEF was 26.6% in the observed HF patients. Most of the clinical characteristics of HFmrEF were intermediate between HFrEF and HFpEF. But a significantly higher ratio of prior myocardial infarction (p = 0.002), ischemic heart disease etiology (p = 0.004), antiplatelet drug use (p = 0.009), angioplasty or stent implantation (p = 0.003) were observed in patients with HFmrEF patients than those with HFpEF and HFrEF. Multivariate analysis showed that the HFmrEF group presented a better prognosis than HFrEF in all-cause mortality [p = 0.022, HR (95%CI): 0.473(0.215-0.887)], cardiovascular mortality [p = 0.005, HR (95%CI): 0.270(0.108-0.672)] and MACE [p = 0.034, OR (95%CI): 0.450(0.215-0.941)] at 1 year. However, no significant differences in 1-year outcomes were observed between HFmrEF and HFpEF. CONCLUSION: HFmrEF is a distinctive subgroup of HF. The strikingly prevalence of ischemic history among patients with HFmrEF might indicate a key to profound understanding of HFmrEF. Patients in HFmrEF group presented better 1-year outcomes than HFrEF group. The long-term prognosis and optimal medications for HFmrEF require further investigations.

[Clinical characteristics of infective endocarditis: analysis of 368 cases].

OBJECTIVE: This retrospective study is performed to analyze the epidemiological and clinical features of patients with infective endocarditis (IE) hospitalized in Fuwai Cardiovascular Hospital during the latest 7 years. METHODS: This retrospective study included a cohort of 368 infective endocarditis patients hospitalized in Fuwai Hospital form August 2005 to August 2012. Predisposing cardiac diseases, causative organisms, clinical features and outcomes were analyzed. Risk factors related to outcome including NYHA classes, causative organisms and complications, were evaluated. RESULTS: Among the IE patients, 6.8% (25/368) patients had rheumatic heart diseases 31.8% (117/368) had congenital heart diseases, 22.8% (84/368) were post-PCI or operative endocarditis and IE developed in 14.1% (52/368) patients without previous cardiac diseases. Blood culture positive rate was 46.2% (170/368). Streptococci viridians [27.6% (47/170) ]were the most common causative organisms, followed by coagulase-negative staphylococci [15.9% (27/170) ]. Fever and cardiac murmur were the most common clinical presentations. Congestive heart failure was the most common complication [87.8% (323/368)]. Systemic and pulmonary embolism occurred in 16.0% patients, 80.9% IE was detected by echocardiography. In-hospital mortality rate was 6.7%, mostly due to refractory congestive heart failure and sepsis. Subgroup analysis showed that incidence of post-PCI or operative endocarditis was significantly higher in IE patients hospitalized after 2009 compared to IE patients hospitalized before 2009 (27.5% vs. 19.2%, P < 0.05) . Higher incidence of staphylococcal infection was evidenced in mechanical valves than in native valves (44.4% vs. 19.8%, P < 0.05). CONCLUSION: During the past decade, there is a significant change on epidemiology and clinical features of IE in China. Incidence of post-surgical and interventional IE increased significantly. Staphylococcal and Gram negative bacilli infection are major pathorganisms of endocarditis of mechanical valves. Due to the lower positive rate of blood culture, echocardiography serves as the most important diagnostic tool for infective endocarditis.

Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development.

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.

Association of inflammatory gene polymorphisms with ischemic stroke in a Chinese Han population.

BACKGROUND: Inflammatory mechanisms are important in stroke risk, and genetic variations in components of the inflammatory response have been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in a Chinese Han population. METHODS: A total of 1,124 ischemic stroke cases and 1,163 controls were genotyped with inflammatory panel strips containing 51 selected inflammatory gene polymorphisms from 35 candidate genes. We tested the genotype-stroke association with logistic regression model. RESULTS: We found two single nucleotide polymorphisms (SNPs) in CCL11 were associated with ischemic stroke. After adjusting for multiple testing using false discovery rate (FDR) with a 0.20 cut-off point, CCL11 rs4795895 remained statistically significant. We further stratified the study population by their hypertension status. In the hypertensive group, CCR2 rs1799864, CCR5 rs1799987 and CCL11 rs4795895 were nominally associated with increased risk of stroke. In the non-hypertensive group, CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 and CCL11 rs4795895 were associated with ischemic stroke. After correction for multiple testing, CCR2 rs1799864 and CCR5 rs1799987 remained significant in the hypertensive group, and CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253 remained significant in the non-hypertensive group. CONCLUSIONS: Our results indicate that inflammatory genetic variants are associated with increased risk of ischemic stroke in a Chinese Han population, particularly in non-hypertensive individuals.

[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.

[Clinical characteristics, treatments and outcome of diabetic patients with non-ST elevation acute coronary syndromes in China].

OBJECTIVE: To observe the clinical characteristics, treatment options and outcome of diabetic patients with non-ST elevation acute coronary syndromes (NSTEACS). METHODS: Consecutive patients admitted with NSTEACS from 38 centers in north China were enrolled. Medical histories, clinical characteristics, treatments and outcomes were evaluated and follow-up was made at 6, 12, and 24 months after their initial hospital admission. Cumulative event rates were compared between diabetic and non-diabetic patients. RESULTS: There were 420 diabetic patients out of 2294 NSTEACS patients (18.3%). Diabetic patients were older [(64.9 ± 6.7) years vs. (62.3 ± 8.6) years, P < 0.01], more often women (48.1% vs. 35.3%, P < 0.05) and were associated with higher baseline comorbidities such as previous hypertension, myocardial infarction, congestive heart failure and stroke than non-diabetic patients. The incidence of antiplatelet therapy (92.1% vs. 95.0%, P < 0.05), coronary angiography (30.0% vs. 36.3%, P < 0.05) and revascularization (12.1% vs.18.8%, P < 0.05) was lower in patients with diabetes than non-diabetic patients. In hospital and 2-year mortality as well as the incidence of congestive heart failure and composite outcomes of myocardial infarction, stroke, congestive heart failure and death were substantially higher in diabetic patients compared with non-diabetic patients. Multivariate Cox regression analysis revealed that age ≥ 70 years, diabetes, previous myocardial infarction, previous congestive heart failure, systolic blood pressure less than 90 mm Hg (1 mm Hg = 0.133 kPa) and heart rate more than 100 bpm at admission were risk factors for 2-year death. CONCLUSION: In NSTEACS, diabetes is associated with higher rate of in-hospital and 2-year death, congestive heart failure and composite outcomes of myocardial infarction, stroke, congestive heart failure and death. Diabetes mellitus is a major independent predictor of 2-year mortality post NSTEACS. Status of antiplatelet therapy, coronary angiography and revascularization should be improved for diabetic patients with NSTEACS during hospitalization.

Elevated Plasma Big Endothelin-1 at Admission Is Associated With Poor Short-Term Outcomes in Patients With Acute Decompensated Heart Failure.

Objective: We aimed to evaluate the association between plasma big endothelin-1 (ET-1) at admission and short-term outcomes in acute decompensated heart failure (ADHF) patients. Methods: In this single-center, retrospective study, a total of 746 ADHF patients were enrolled and divided into three groups according to baseline plasma big ET-1 levels: tertile 1 (<0.43 pmol/L, n = 250), tertile 2 (between 0.43 and 0.97 pmol/L, n = 252), and tertile 3 (>0.97 pmol/L, n = 244). The primary outcomes were all-cause death, cardiac arrest, or utilization of mechanical support devices during hospitalization. Logistic regression analysis and net reclassification improvement approach were applied to assess the predictive power of big ET-1 on short-term outcomes. Results: During hospitalization, 92 (12.3%) adverse events occurred. Etiology, arterial pH, lactic acid, total bilirubin, serum creatine, serum uric acid, presence of atrial fibrillation and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with plasma big ET-1 level, whereas systolic blood pressure, serum sodium, hemoglobin, albumin, and estimated glomerular filtration rate were negatively correlated. In multivariate logistic regression, tertile 3 compared with tertile 1 had a 3.68-fold increased risk of adverse outcomes [odds ratio (OR) = 3.681, 95% confidence interval (CI) 1.410-9.606, p = 0.008]. However, such adverse effect did not exist between tertile 2 and tertile 1 (OR = 0.953, 95% CI 0.314-2.986, p = 0.932). As a continuous variable, big ET-1 level was significantly associated with primary outcome (OR = 1.756, 95% CI 1.413-2.183, p < 0.001). The C statistic of baseline big ET-1 was 0.66 (95% CI 0.601-0.720, p < 0.001). Net reclassification index (NRI) analysis showed that big ET-1 provided additional predictive power when combining it to NT-proBNP (NRI = 0.593, p < 0.001). Conclusion: Elevated baseline big ET-1 is an independent predictor of short-term adverse events in ADHF patients and may provide valuable information for risk stratification.

Fulminant Giant Cell Myocarditis vs. Lymphocytic Myocarditis: A Comparison of Their Clinical Characteristics, Treatments, and Outcomes.

Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM). Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0-10.2) mg/L vs. 13.6 (12.6-14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0-3.2) ng/ml vs. 14.6 (3.0-64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0-61.5) IU/L vs. 997.0 (50.0-3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761-0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213-0.9964). Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.

Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors.

Brain tumor is the leading cause of cancer related death in children. Clinically relevant animals are critical for new therapy development. To address the potential impact of animal gender on tumorigenicity rate, xenograft growth and in vivo drug responses, we retrospectively analyzed 99 of our established patient derived orthotopic xenograft mouse models (orthotopic PDX or PDOX). From 27 patient tumors, including 5 glioblastomas (GBMs), 11 medulloblastomas (MBs), 4 ependymomas (EPNs), 4 atypical teratoid/rhabdoid tumors (ATRTs) and 3 diffuse intrinsic pontine gliomas (DIPGs), that were directly implanted into matching locations in the brains of approximately equal numbers of male and female animals (n = 310) in age-matched (within 2-week age-difference) SCID mice, the tumor formation rate was 50.6 ± 21.5% in male and 52.7 ± 23.5% in female mice with animal survival times of 192.6 ± 31.7 days in male and 173.9 ± 34.5 days in female mice (P = 0.46) regardless of pathological diagnosis. Once established, PDOX tumors were serially subtransplanted for up to VII passage. Analysis of 1,595 mice from 59 PDOX models (18 GBMs, 18 MBs, 5 ATRTs, 6 EPNs, 7 DIPGs and 5 PENTs) during passage II and VII revealed similar tumor take rates of the 6 different tumor types between male (85.4 ± 15.5%) and female mice (84.7 ± 15.2%) (P = 0.74), and animal survival times were 96.7 ± 23.3 days in male mice and 99.7 ± 20 days in female (P = 0.25). A total of 284 mice from 7 GBM, 2 MB, 1 ATRT, 1 EPN, 2 DIPG and 1 PNET were treated with a series of standard and investigational drugs/compounds. The overall survival times were 106.9 ± 25.7 days in male mice, and 110.9 ± 31.8 days in female mice (P = 0.41), similar results were observed when different types/models were analyzed separately. In conclusion, our data demonstrated that the gender of SCID mice did not have a major impact on animal model development nor drug responses in vivo, and SCID mice of both genders are appropriate for use.

[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.

[Predictive value of admission amino-terminal pro-B-type natriuretic peptide on in-hospital mortality in patients with decompensated heart failure].

OBJECTIVE: To evaluate the predictive value of admission plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) on in-hospital mortality in patients with decompensated heart failure. METHODS: Plasma NT-proBNP levels were measured in patients with decompensated heart failure within 24 hours after admission with ELISA method. The NT-proBNP levels were compared between survivals and dying patients in hospital. ROC analyses were performed to evaluate the predictive value of admission plasma NT-proBNP on in-hospital mortality and to identify the optimal NT-proBNP cut-point for predicting in-hospital mortality. A binary logistic regress analyses was used to evaluate if NT-proBNP was an independent predictor for in-hospital mortality. RESULTS: A total of 804 patients with decompensated heart failure were enrolled in his study (293 valvular heart diseases, 219 ischemic cardiomyopathy, 141 dilated cardiomyopathy, 14 hypertrophic cardiomyopathy, 21 restrictive cardiomyopathy, 39 hypertensive heart disease, 41 chronic pulmonary heart disease and 36 adult congenital heart disease) and 96 patients were in class II, 450 in class III and 258 in cases IV according to NYHA Classification. During hospitalization, 64 deaths were recorded and the on admission plasma NT-proBNP levels of patients died during hospitalization were significantly higher than those of survivals [4321.1 (3063.8, 6606.5) pmol/L vs. 1921.6 (873.9, 3739.2) pmol/L, P<0.01]. Area under receiver operating characteristic curve (AUC) of NT-proBNP to predict in-hospital death was 0.772 (95% CI: 0.718 - 0.825, P<0.01), the optimal plasma NT-proBNP cut-point for predicting in-hospital mortality was 3500 pmol/L, with a sensitivity of 70.3%, a specificity of 72.0%, an accuracy of 71.9%, a positive predictive value of 17. 8% and a negative predictive value of 96.6%. Patients whose NT-proBNP levels were equal or more than 3500 pmol/L had a much higher in-hospital mortality (17.8%) compared with those with NT-proBNP levels of less than 3500 pmol/L (3.4%), P<0.01. Binary logistic regress analyses demonstrated that admission plasma NT-proBNP, pneumonia, heart rate and NYHA class were independent predictors for in-hospital mortality in patients with decompensated heart failure (P<0.05 or 0.01) and admission plasma NT-proBNP was the strongest predictor for in-hospital mortality. CONCLUSIONS: Admission plasma NT-proBNP level was an independent predictor for in-hospital mortality in patients with decompensated heart failure. The optimal NT-proBNP cut-point for predicting in-hospital mortality was 3500 pmol/L in this patient cohort.

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy.

BACKGROUND: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy. METHODS: Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy. RESULTS: A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified. CONCLUSIONS: We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

[The Chinese registry on reperfusion strategies and outcomes in ST-elevation myocardial infarction].

OBJECTIVE: To analyze the current use of reperfusion strategies and the outcomes of patients with ST elevation acute coronary syndromes (ACS) in China. METHODS: A total of 518 consecutive patients (371 male and 147 females, mean age 65 +/- 11) with ST elevation ACS or newly discovered left bundle branch block were registered from 20 hospitals from 5 regions (ranging from large regional centre hospitals to small county hospitals) in China. Patient general characteristics, reperfusion patterns and outcomes were analyzed. Patients were followed up for 3 months. RESULTS: The median time from pain onset to presentation at the hospital was 4 hours. Pre-hospital delay > 12 hours was found in 20% patients. Fifty-six percent patients (292/518) underwent reperfusion therapy (134 with primary percutaneous coronary intervention and 158 with fibrinolysis). The median time from admission to reperfusion (door-to-needle) was 65 min in fibrinolysis group and 110 min (door-to-cath) in primary PCI group respectively. Urokinase was used in 67% (106/158) patients underwent fibrinolysis. Multivariate logistic regression analysis showed that age >/= 75 years (P < 0.01), previous myocardial infarction (P < 0.01) and history of congestive heart failure (P < 0.05) were associated with no reperfusion therapy. Mortality and congestive heart failure rates were significantly higher in patients with no reperfusion therapy not only at discharge (P < 0.01) but also at 3 months (P < 0.01) compared to patients underwent reperfusion. The incidence of combined outcomes (death or MI, and death, MI or Strobe) was also higher in patients without reperfusion therapy at 3 months (all P < 0.01) compared to patients underwent reperfusion. There were no differences on combined outcomes between fibrinolysis and primary PCI subgroups. CONCLUSION: Reperfusion therapy was the primary treatment of choice to improve the outcomes of patients with ST elevation ACS. Strategies to increase reperfusion therapy rate for ST elevation ACS are urgently needed in China.

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.

Serum Potassium Levels and Short-Term Outcomes in Patients With ST-Segment Elevation Myocardial Infarction.

Current guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L (1 mEq/L = mmol/L) in patients with acute myocardial infarction. However, these guidelines are based on studies conducted before the ß blocker and reperfusion era. We retrospectively analyzed 6613 patients diagnosed with ST-segment elevation myocardial infarction (STEMI) who presented without renal insufficiency. Patients were categorized into 5 groups according to mean serum potassium levels: <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/L. Patients with potassium levels of 4.0 to <4.5 mEq/L had the lowest predefined event rates, which were 6.4% for 7-day malignant arrhythmia, 3.7% for 7-day mortality, and 5.3% for 30-day mortality. Compared with the reference group (4.0 to <4.5 mEq/L), multivariate regression analysis revealed significantly higher 30-day mortality risk in patients with potassium level of 4.5 to <5.0 (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.17-1.98; P = .002) and even higher risk in patients with potassium level of ≥5.0 mEq/L (HR: 1.80, 95% CI: 1.22-2.66; P = .002). The lowest 30-day mortality was observed in patients with STEMI having potassium levels between 4.0 and 4.5 mEq/L, and a level >4.5 mEq/L significantly increased mortality risk.