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.

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.

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.

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.

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.

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.

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.

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.

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.).

Comparison of 4 Admission Blood Pressure Indexes for Predicting 30-Day Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: We compared admission systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting 30-day all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock. METHODS: A retrospective study was performed in 7,033 consecutive STEMI patients. Multivariate-adjusted hazard ratios (HRs) with a 10mm Hg increment and quartiles of each blood pressure were determined by Cox proportional hazard analyses; Wald χ (2) tests were used to compare the strength of relationships. RESULTS: Totally 593 (8.4%) patients died during follow-up. Of 4 indexes, only SBP (HR 0.94 per 10mm Hg, 95% confidence interval (CI) 0.91 to 0.98; P = 0.001) and PP (HR 0.89 per 10 mmHg, 95% CI 0.85 to 0.94; P < 0.001) were significantly associated with 30-day all-cause mortality; these in the highest vs. lowest quartiles of SBP (≥140 vs. <110mm Hg) and PP (≥60 vs. <40mm Hg) had HRs of mortality of 0.70 (95% CI 0.55 to 0.87; P = 0.003) and 0.60 (95% CI 0.47 to 0.75; P < 0.001), respectively. Compared with SBP, PP was a better predictor for mortality no matter in men (χ (2) = 5.9 for per 10mm Hg, χ (2) = 10.8 for quartiles) or women (χ (2) = 15.1 for per 10mm Hg, χ (2) = 19.5 for quartiles), and the relationship remained significant after adjustment of SBP. There was a pattern of declining risk with increasing blood pressures for mortality, and this trend was mainly observed in age groups of more than 70 years. CONCLUSIONS: Pulse pressure was an independent predictor of mortality in patients with STEMI, and low admission blood pressure should serve as a warning sign.

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.

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.

Impact of Admission Systolic Blood Pressure and Antecedent Hypertension on Short-Term Outcomes After ST-Segment Elevation Myocardial Infarction: Strobe-Compliant Article.

We evaluated the combined effect of admission systolic blood pressure (SBP) and antecedent hypertension on short-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Data were derived from a multicenter survey of 7303 consecutive patients with STEMI. Patients were divided into 4 groups according to different blood pressure status: high SBP without hypertension, high SBP with hypertension, low SBP without hypertension, and low SBP with hypertension. The primary endpoints were 7 and 30-day all-cause mortality. The prevalence of hypertension was 40.7%, and the best cutoff of admission SBP for predicting 30-day mortality was 108 mmHg by receiver-operating characteristic curve. Patients with hypertension were older, more often female, also had longer onset-to-admission time, more comorbidities, and higher Killip class. Patients with both low SBP (≤108 mmHg) and hypertension group had significantly higher 7 and 30-day mortality than those in other groups (all P < 0.001). After multivariate adjustment, low SBP with hypertension group was still an independent risk factor for predicting 7-day mortality (hazard ratios [HR] 1.86, 95% confidence interval [CI] 1.41-2.46; P < 0.001) and 30-day mortality (HR 1.88, 95% CI 1.46-2.43; P < 0.001). In patients with SBP > 108 mmHg, a history of hypertension could increase the risk of 30-day mortality by 27% (HR 1.00 vs 1.27, P = 0.012), while in patients with SBP ≤ 108 mmHg, this increased risk reached to 37% (HR 1.51 vs 1.88, P < 0.001). In conclusion, low admission SBP was the relatively dominant contributor for predicting 7 and 30-day all-cause mortality, and a concurrent antecedent hypertension increased the corresponding risk of mortality.

Association of Admission Glycaemia With High Grade Atrioventricular Block in ST-Segment Elevation Myocardial Infarction Undergoing Reperfusion Therapy: An Observational Study.

Several studies have demonstrated the association between elevated admission glycaemia (AG) and the occurrence of some arrhythmias such as atrial fibrillation, ventricular tachycardia, and ventricular fibrillation after myocardial infarction. However, the impact of elevated AG on the high grade atrioventricular block (AVB) occurrence after ST-segment elevation myocardial infarction (STEMI) remains unclear. Included were 3359 consecutive patients with STEMI who received reperfusion therapy. The primary endpoint was the development of high grade AVB during hospital course. Patients were divided into non-diabetes mellitus (DM), newly diagnosed DM, and previously known DM according to the hemoglobin A1c level. The optimal AG value was determined by receiver operating characteristic curves analysis with AG predicting the high grade AVB occurrence. The best cut-off value of AG for predicting the high grade AVB occurrence was 10.05 mmol/L by ROC curve analysis. The prevalence of AG ≥ 10.05 mmol/L in non-DM, newly diagnosed DM, and previously known DM was 15.7%, 34.1%, and 68.5%, respectively. The incidence of high grade AVB was significantly higher in patients with AG ≥ 10.05  mmol/L than <10.05  mmol/L in non-DM (5.7% vs. 2.1%, P < 0.001) and in newly diagnosed DM (10.2% vs.1.4%, P < 0.001), but was comparable in previously known DM (3.6% vs. 0.0%, P = 0.062). After multivariate adjustment, AG ≥ 10.05  mmol/L was independently associated with increased risk of high grade AVB occurrence in non-DM (HR = 1.826, 95% CI 1.073-3.107, P = 0.027) and in newly diagnosed DM (HR = 5.252, 95% CI 1.890-14.597, P = 0.001). Moreover, both AG ≥ 10.05  mmol/L and high grade AVB were independent risk factors of 30-day all cause-mortality (HR = 1.362, 95% CI 1.006-1.844, P = 0.046 and HR = 2.122, 95% CI 1.154-3.903, P = 0.015, respectively). Our study suggested that elevated AG level (≥10.05  mmol/L) might be an indicator of increased risk of high grade AVB occurrence in patients with STEMI.

Impact of initial 24-h urine output on short-term outcomes in patients with ST-segment elevation myocardial infarction admitted without cardiogenic shock and renal dysfunction.

OBJECTIVES: Our study aims to evaluate the prognostic value of initial 24-h urine output (UO) in patients with ST-segment elevation myocardial infarction (STEMI) admitted without cardiogenic shock and renal dysfunction, and to determine the additional risk stratification offered by adding initial 24-h UO to TIMI risk score (TRS). METHODS: Data from 7078 consecutive STEMI patients in a multi-center registry were retrospectively analyzed. Patients were divided into 4 groups according to initial 24-h UO quartiles. The primary endpoints were 7- and 30-day all-cause mortality. RESULTS: Patients in the lowest UO quartile (≤1020 mL) had significantly higher 7- and 30-day all-cause mortality rates, cardiogenic shock, and major adverse cardiovascular events (MACE) than those in other groups (all P<0.05). After multivariate adjustment, initial 24-h UO≤1020 mL was independently associated with an increased risk in 7-day all-cause mortality (HR=4.649, 95%CI 3.348-6.455) and 30-day all-cause mortality (HR=3.775, 95%CI 2.891-4.931) as well as 7-day MACE (HR=1.845, 95%CI 1.563-2.179) and 30-day MACE (HR=1.818, 95%CI 1.553-2.127). Initial 24-h UO provided additional risk stratification across all TRS groups and improved the discriminatory ability of TRS with respect to 7-day all-cause mortality (c-statistic from 0.704 to 0.764) and 30-day all-cause mortality (c-statistic from 0.706 to 0.743). CONCLUSION: Reduced initial 24-h UO (≤1020 mL) was associated with an increased risk in 7- and 30-day all-cause mortality and MACE in STEMI patients admitted without cardiogenic shock and renal dysfunction. The combination of initial 24-h UO and TRS improved short-term outcome prediction when compared to TRS alone, particularly in patients with initial 24-h UO≤1020 mL.

One-Year Outcomes of Emergency Department Patients With Atrial Fibrillation: A Prospective, Multicenter Registry in China.

There is lack of data about patient characteristics, practice patterns, and long-term adverse outcomes in patients with atrial fibrillation (AF) attending emergency departments (EDs) in China. A total of 2016 patients from 20 representative EDs were included. During 1 year, all-cause mortality was 291 (14.6%) cases, stroke/noncentral nervous system systemic embolism rate was 159 (8.0%) cases, and major bleeding was 26 (1.3%) cases. Heart failure, the major cause of mortality, accounted for 43.0% of deaths. Of 375 (18.6%) patients who used warfarin at baseline, only 217 (57.9%) patients were still on anticoagulation therapy during 1-year follow-up. Compared with the patients who continued on warfarin, the mortality rate was higher in those who did not continue (15.9% vs 5.5%, P < .001). Patients seen in ED with AF appear to have a high incidence rate of long-term all-cause mortality and inadequate anticoagulation rate.