Postoperative Dipping Patterns of Mean Arterial Pressure and Mortality After Coronary Artery Bypass Grafting.

Blood pressure dipping patterns have long been considered to be associated with adverse events. We aimed to investigate whether dipping patterns of postoperative MAP were related to 90-day and hospital mortality in patients undergoing CABG. Four thousand three hundred ninety-one patients were classified into extreme dippers (night-to-day ratio of MAP ≤ 0.8), dippers (0.8 < night-to-day ratio of MAP ≤ 0.9), non-dippers (0.9 < night-to-day ratio of MAP ≤ 1), and reverse dippers (> 1). Compared with non-dippers, reverse dippers were at a higher risk of 90-day mortality (aHR = 1.58; 95% CI, 1.10-2.27) and hospital mortality (aOR = 1.97; 95% CI, 1.12-3.47). A significant interaction was observed between hypertension and dipping patterns (P for interaction = 0.02), with a significant increased risk of 90-day mortality in non-hypertensive reverse dippers (aHR = 1.90; 95% CI, 1.17-3.07) but not in hypertensive reverse dippers (aHR = 1.26; 95% CI, 0.73-2.19).

Development and validation of a postoperative bleeding complications prediction model in infective endocarditis.

OBJECTIVES: Bleeding complications are one of the most serious postoperative complications after cardiac surgery and are associated with high mortality, especially in patients with infective endocarditis (IE). Our objectives were to identify the risk factors and develop a prediction model for postoperative bleeding complications in IE patients. METHODS: The clinical data of IE patients treated from October 2013 to January 2022 were reviewed. Multivariate logistic regression analysis was used to evaluate independent risk factors for postoperative bleeding complications and develop a prediction model accordingly. The prediction model was verified in a temporal validation cohort. The performance of the model was evaluated in terms of its discrimination power, calibration, precision, and clinical utility. RESULTS: A total of 423 consecutive patients with IE who underwent surgery were included in the final analysis, including 315 and 108 patients in the training cohort and validation cohort, respectively. Four variables were selected for developing a prediction model, including platelet counts, systolic blood pressure, heart failure and vegetations on the mitral and aortic valves. In the training cohort, the model exhibited excellent discrimination power (AUC = 0.883), calibration (Hosmer-Lemeshow test, P = 0.803), and precision (Brier score = 0.037). In addition, the model also demonstrated good discrimination power (AUC = 0.805), calibration (Hosmer-Lemeshow test, P = 0.413), and precision (Brier score = 0.067) in the validation cohort. CONCLUSIONS: We developed and validated a promising risk model with good discrimination power, calibration, and precision for predicting postoperative bleeding complications in IE patients.

Impact of heart failure and preoperative platelet count on the postoperative short-term outcome in infective endocarditis patients.

BACKGROUND: Heart failure (HF) and platelet count are often considered risk factors for mortality in patients with infective endocarditis (IE); however, their effects on various complications have not been elucidated. HYPOTHESIS: We speculated that HF and platelet count have significant impact on the short-term outcomes of IE. METHODS: This single-center retrospective study analyzed data from 320 IE patients who underwent surgery. A multivariate Cox proportional hazards model was used to identify the risk factors for adverse outcomes. The effect of the platelet count on the prognosis of patients with HF was determined by subgroup analysis and Kaplan-Meier analysis. RESULTS: The study population was divided into the HF group (n = 102) and the non-HF group (n = 218). The median age of the total population was 44.5 years (31-56 years), of which 227 (70.94%) patients were male. The incidence rates of 1-year all-cause mortality, cardiac outcomes, and composite outcomes were respectively almost sixfold, fourfold, and threefold higher in the HF group than in the non-HF group (all p < 0.001). In multivariate Cox regression analysis, HF was an independent risk factor for 1-year all-cause mortality, cardiac outcomes, cerebral outcomes, and composite outcomes. The Kaplan-Meier survival curves revealed that the patients with both HF and thrombocytopenia demonstrated the worst composite outcomes than the patients of the other groups (log-rank p < 0.001). In the HF group, the platelet count was significantly associated with mortality and composite outcomes. CONCLUSIONS: HF and preoperative platelet count are significantly associated with 1-year all-cause mortality and adverse outcomes postoperatively in IE patients. Patients with HF and thrombocytopenia have the worst short-term prognosis.

Predictors of short-term survival in cardiac valvular surgery patients with intra-aortic balloon pump implantation.

BACKGROUND: Intro-aortic balloon pump (IABP) is widely used in cardiac surgery patients nowadays. This study aimed to analyze the predictor of short-term survival in cardiac valvular surgery patients with intra-aortic balloon pump implantation. METHODS: This was a retrospective study and a total of 102 cardiac valvular surgery patients who received intra-aortic balloon pump implantation were consecutively included. We retrospectively collected the baseline characteristics and short-term outcomes. Baseline characteristics were compared between survivors with non-survivors, and logistic regression was performed to identify predictors for short-term mortality. RESULTS: Among all the patients, there were 71 (69.6%) patients successfully weaned from IABP and survived to discharge, the other 31 (30.4%) patients failed to wean from IABP and died within the first 30 days after surgery. When compared with non-survivors, survivors had a higher proportion of males (62% vs 32.3%, p = 0.006), a lower rate of Atrial fibrillation (38% vs 62%, p < 0.03). After IABP implantation, vasoactive drug use was significantly lower in survivors compared with non-survivors, and survivors showed significant improvements in cardiac function and urine volume. Univariate and multivariate logistic regression analysis indicated that atrial fibrillation and combined use of continuous renal replacement therapy (CRRT) were significant independent predictors for short-term mortality. CONCLUSION: Timely implantation of IABP can improve patients' cardiac and renal function and reduce the dosage of vasoactive drugs. Atrial fibrillation and combined use of CRRT are independent predictors for short-term mortality in patients who underwent cardiac valvular surgery with IABP implantation.

Risk factors for mortality in surgical patients on combined continuous renal replacement therapy and extracorporeal membrane oxygenation: single-center retrospective study.

OBJECTIVE: In patients receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT) is increasingly being used for renal replacement and fluid management. However, critically ill surgical patients receiving combined ECMO and CRRT tend to have a high mortality rate, and there are limited studies on this population. Therefore, we aimed to investigate the risk factors for mortality in surgical patients receiving combined ECMO and CRRT. METHODS: Data of surgical patients who underwent ECMO between December 2013 and April 2023 were retrospectively reviewed. Univariate and multivariate logistic regression analysis were used to identify the risk variables. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of albumin and age to predict death. RESULTS: A total of 199 patients on ECMO support were screened, of which 105 patients were included in the final analysis. Of 105 patients, 77 (73.33%) were treated with CRRT. Veno-arterial ECMO was performed in 97 cases (92.38%), and the rest were veno-venous ECMO (n = 8, 7.62%). Cardiovascular-related surgery was performed in the main patients (n = 86, 81.90%) and other types of surgery in 19 patients. In surgical patients on ECMO support, the logistic regression analysis showed that CRRT implantation, male sex, and age were the independent risks factors for mortality. Furthermore, the ROC curve analysis showed that age 48.5 years had the highest Youden index. In surgical patients on combined CRRT and ECMO, age, valvular heart disease, and albumin were the independent risk factors for prognosis. Albumin had the highest Youden index at a cutoff value of 39.95 g/L for predicting mortality, though the overall predictive value was modest (area under ROC 0.704). Age had the highest Youden index at a cutoff value of 48.5 years for predicting mortality. CONCLUSIONS: In our cohort of surgical patients requiring ECMO, which consisted mostly of patients undergoing cardiovascular surgery requiring VA-ECMO, the need for CRRT was an independent risk factor for mortality. In the subset of patients on combined CRRT and ECMO, independent risk factors for mortality included higher age, lack of valvular heart disease, and lower serum albumin.

Clinical Effects of Surgical Left Atrial Reduction and Concomitant Mitral Valve Replacement in Patients with Giant Left Atrium.

INTRODUCTION: A giant left atrium may cause respiratory dysfunction and hemodynamic disturbance postoperatively. This retrospective study aimed to evaluate clinical effects of surgical left atrial reduction in concomitant cardiac valves operations. METHODS: One hundred and thirty-five patients with heart valve diseases and giant left atriums from January 2004 to July 2021 were enrolled into this research. They were divided into the folded group (n=63) and the unfolded group (n=72). Patients in the folded group had undergone cardiac valve operations concomitantly with left atrial reductions. The perioperative characteristics were compared between both groups, and subgroup analysis was performed. RESULTS: There were five deaths in the folded group and 25 deaths in the unfolded group (P<0.001). Complications including pneumonia, sepsis, multiple organs dysfunction syndrome, low cardiac output syndrome, and the use of continuous renal replacement therapy were significantly fewer in the folded group. The receiver operating characteristic curve of left atrial max. diameter predicting mortality was significant (area under the curve=0.878, P=0.005), and the cutoff point was 96.5 mm. The stratified analysis for sex showed that more female patients died in the unfolded group. Logistic regression for mortality showed that the left atrium unfolded, left atrial max. diameter, cardiopulmonary bypass time, and mechanical ventilation time increased the risk of death. CONCLUSION: Surgical left atrial reduction concomitantly with valves replacement could decrease mortality and was safe and effective in giant left atrium patients.

M2b macrophages protect against doxorubicin induced cardiotoxicity via alternating autophagy in cardiomyocytes.

OBJECTIVE: Doxorubicin (DOX) is an anthracycline antibiotic which is widely used for the treatment of various cancers, while the dose-related cardiotoxicity limits its potential therapeutic application. The underlying mechanism of DOX induced cardiotoxicity is complex and remains elusive. Our previous studies have shown that M2b macrophage plays an important role in reducing inflammation due to ischemic reperfusion injury in the myocardium. The purpose of this study was to investigate the potential protective role of M2b macrophages in DOX induced cardiotoxicity. METHODS: In vivo, we conducted DOX induced cardiac injury in C57BL/6 mice and treated them with M2b macrophages. Then, the mice were examined by echocardiography. The heart specimens were harvested for histological examination, transmission electron microscope analysis, and autophagy molecules evaluation. In vitro, HL-1 cardiac cell lines treated with DOX were cocultured with or without M2b macrophages. Then, Autophagy related genes and protein expression were assessed by real-time quantitative PCR and western blot; cell proliferation was assessed by cell counting kit-8. RESULTS: We found that M2b macrophages can improve cardiac function and alleviate cardiac injury in DOX induced cardiac injury mice. M2b macrophages can enhance cardiac autophagy levels both in vivo and in vitro in DOX induced cardiac injury model. In addition, this protective effect can be blocked by an autophagy inhibitor. CONCLUSION: Our study shows that M2b macrophages can help attenuate the DOX induced cardiotoxicity by regulating the autophagy level of cardiomyocytes.

L1 cell adhesion molecule may be a protective molecule for atrial fibrillation in patients with valvular heart disease.

Background: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia. L1 cell adhesion molecule (L1CAM) served as a crucial regulator of signaling pathways. This research sought to examine the clinical value and functions of soluble L1CAM in the serum of AF patients. Methods: In total, 118 patients (valvular heart disease patients [VHD, total: n = 93; AF: n = 47; sinus rhythm (SR): n = 46] and healthy controls [n = 25]) were recruited in this retrospective study. Plasma levels of L1CAM were detected by enzyme-linked immunosorbent assays. The Pearson's correlation approach, as applicable, was used for analyzing the correlations. The L1CAM was shown to independently serve as a risk indicator of AF in VHD after being analyzed by the multivariable logistic regression. To examine the specificity and sensitivity of AF, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used. A nomogram was developed for the visualisation of the model. We further evaluate the prediction model for AF using calibration plot and decision curve analysis. Results: The plasma level of L1CAM was substantially decreased in AF patients as opposed to healthy control and SR patients (healthy control = 46.79 ± 12.55 pg/ml, SR = 32.86 ± 6.11 pg/ml, AF = 22.48 ± 5.39 pg/ml; SR vs. AF, P < 0.001; control vs. AF, P < 0.001). L1CAM was significantly and negatively correlated with LA and NT-proBNP (LA: r = -0.344, P = 0.002; NT-proBNP: r = -0.380, P = 0.001). Analyses using logistic regression showed a substantial correlation between L1CAM and AF in patients with VHD (For L1CAM, Model 1: OR = 0.704, 95%CI = 0.607-0.814, P < 0.001; Model 2: OR = 0.650, 95% CI = 0.529-0.798, P < 0.001; Model 3: OR = 0.650, 95% CI = 0.529-0.798, P < 0.001). ROC analysis showed that inclusion of L1CAM in the model significantly improved the ability of other clinical indicators to predict AF. The predictive model including L1CAM, LA, NT-proBNP and LVDd had excellent discrimination and a nomogram was developed. The model had good the calibration and clinical utility. Conclusion: L1CAM was shown to independently serve as a risk indicator for AF in VHD. In AF patients with VHD, the prognostic and predictive effectiveness of models incorporating L1CAM was satisfactory. Collectively, L1CAM may be a protective molecule for atrial fibrillation in patients with valvular heart disease.

Evolution, coronary artery bypass surgery and outcomes of right ventricular dysfunction in ischaemic cardiomyopathy.

OBJECTIVES: Whether the presence or evolution of right ventricular dysfunction (RVD) affects the prognosis and the therapeutic choice between coronary artery bypass grafting (CABG) or medical therapy alone in patients with ischaemic cardiomyopathy (ICM) remains unclear. We investigate the prognostic and therapeutic implications of RVD in patients with ICM. METHODS: Patients with baseline echocardiographic right ventricular (RV) assessment were included from the Surgical Treatment of Ischaemic Heart Failure trial. The primary outcome was all-cause mortality. RESULTS: Of 1212 patients enrolled in the Surgical Treatment of Ischaemic Heart Failure trial, 1042 patients were included, with 143 (13.7%) mild RVD and 142 (13.6%) moderate-to-severe RVD. After a median follow-up of 9.8 years, compared with patients with normal RV function, patients with RVD had a higher risk of mortality [mild RVD: adjusted hazard ratio (aHR) 1.32; 95% confidence interval (CI) 1.06-1.65; moderate-to-severe RVD: aHR, 1.75; 95% CI 1.40-2.19]. Among patients with moderate-to-severe RVD, CABG provided no additional survival benefits compared to medical therapy alone (aHR: 0.98; 95% CI: 0.67-1.43). Among 746 patients with pre- and post-therapeutic RV assessment, a gradient risk for death increased from patients with consistent normal RV function, to patients with recovery from RVD, new-onset RVD and persistent RVD. CONCLUSIONS: RVD was associated with a worse prognosis in patients with ICM, and CABG provided no additional survival benefits to patients with moderate-to-severe RVD. The evolution of RV function had important prognostic implications, which emphasized the importance of both pre- and post-therapeutic RV assessment.

Systolic blood pressure time in target range and long-term outcomes in patients with ischemic cardiomyopathy.

BACKGROUND: The relationship between the degree of systolic blood pressure (SBP) control and outcomes remains unclear in patients with ischemic cardiomyopathy (ICM). Current control metrics may not take into account the potential effects of SBP fluctuations over time on patients. METHODS: This study was a post-hoc analysis of the surgical treatment of ischemic heart failure trial which enrolled 2,136 participants with ICM. Our SBP target range was defined as 110 to 130 mm Hg and the time in target range (TTR) was calculated by linear interpolation. RESULTS: A total of 1,194 patients were included. Compared with the quartile 4 group (TTR 77.87%-100%), the adjusted hazard ratios and 95% confidence intervals of all-cause mortality were 1.32 (0.98-1.78) for quartile 3 group (TTR 54.81%-77.63%), 1.40 (1.03-1.90) for quartile 2 group (TTR 32.59%-54.67%), and 1.53 (1.14-2.04) for quartile 1 group (TTR 0%-32.56%). Per 29.28% (1-SD) decrement in TTR significantly increased the risk of all-cause mortality (1.15 [1.04-1.26]). Similar results were observed in the cardiovascular (CV) mortality and the composite outcome of all-cause mortality plus CV rehospitalization, and in the subgroup analyses of either coronary artery bypass grafting or medical therapy, and different baseline SBP. CONCLUSIONS: In patients with ICM, the higher TTR was significantly associated with decreased risk of all-cause mortality, CV mortality and the composite outcome of all-cause mortality plus CV rehospitalization, regardless of whether the patient received coronary artery bypass grafting or medical therapy, and the level of baseline SBP. TTR may be a surrogate metric of long-term SBP control in patients with ICM.

Reduced Angiopoietin Factor 2 Levels Are Correlated with Better Cardiac Function and Prognosis in Valvular Heart Disease

ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

Reduced Angiopoietin Factor 2 Levels Are Correlated with Better Cardiac Function and Prognosis in Valvular Heart Disease.

INTRODUCTION: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. METHODS: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. RESULTS: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients - but not NYHA III/IV patients - was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). CONCLUSION: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

Clinical Effects of Surgical Left Atrial Reduction and Concomitant Mitral Valve Replacement in Patients with Giant Left Atrium

ABSTRACT Introduction: A giant left atrium may cause respiratory dysfunction and hemodynamic disturbance postoperatively. This retrospective study aimed to evaluate clinical effects of surgical left atrial reduction in concomitant cardiac valves operations. Methods: One hundred and thirty-five patients with heart valve diseases and giant left atriums from January 2004 to July 2021 were enrolled into this research. They were divided into the folded group (n=63) and the unfolded group (n=72). Patients in the folded group had undergone cardiac valve operations concomitantly with left atrial reductions. The perioperative characteristics were compared between both groups, and subgroup analysis was performed. Results: There were five deaths in the folded group and 25 deaths in the unfolded group (P<0.001). Complications including pneumonia, sepsis, multiple organs dysfunction syndrome, low cardiac output syndrome, and the use of continuous renal replacement therapy were significantly fewer in the folded group. The receiver operating characteristic curve of left atrial max. diameter predicting mortality was significant (area under the curve=0.878, P=0.005), and the cutoff point was 96.5 mm. The stratified analysis for sex showed that more female patients died in the unfolded group. Logistic regression for mortality showed that the left atrium unfolded, left atrial max. diameter, cardiopulmonary bypass time, and mechanical ventilation time increased the risk of death. Conclusion: Surgical left atrial reduction concomitantly with valves replacement could decrease mortality and was safe and effective in giant left atrium patients.

Quantification of Gut Microbiota Dysbiosis-Related Organic Acids in Human Urine Using LC-MS/MS.

Urine organic acid contains water-soluble metabolites and/or metabolites­derived from sugars, amino acids, lipids, vitamins, and drugs­which can reveal a human's physiological condition. These urine organic acids­hippuric acid, benzoic acid, phenylacetic acid, phenylpropionic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyl acetic acid, 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl propionic acid, and 3-indoleacetic acid­were the eligible candidates for the dysbiosis of gut microbiota. The aim of this proposal was to develop and to validate a liquid chromatography−tandem mass spectrometry (LC-MS/MS) bioanalysis method for the nine organic acids in human urine. Stable-labeled isotope standard (creatinine-d3) and acetonitrile were added to the urine sample. The supernatant was diluted with deionized water and injected into LC-MS/MS. This method was validated with high selectivity for the urine sample, a low limit of quantification (10−40 ng/mL), good linearity (r > 0.995), high accuracy (85.8−109.7%), and high precision (1.4−13.3%). This method simultaneously analyzed creatinine in urine, which calibrates metabolic rate between different individuals. Validation has been completed for this method; as such, it could possibly be applied to the study of gut microbiota clinically.

Machine Learning-Based Risk Model for Predicting Early Mortality After Surgery for Infective Endocarditis.

Background The early mortality after surgery for infective endocarditis is high. Although risk models help identify patients at high risk, most current scoring systems are inaccurate or inconvenient. The objective of this study was to construct an accurate and easy-to-use prediction model to identify patients at high risk of early mortality after surgery for infective endocarditis. Methods and Results A total of 476 consecutive patients with infective endocarditis who underwent surgery at 2 centers were included. The development cohort consisted of 276 patients. Eight variables were selected from 89 potential predictors as input of the XGBoost model to train the prediction model, including platelet count, serum albumin, current heart failure, urine occult blood ≥(++), diastolic dysfunction, multiple valve involvement, tricuspid valve involvement, and vegetation >10 mm. The completed prediction model was tested in 2 separate cohorts for internal and external validation. The internal test cohort consisted of 125 patients independent of the development cohort, and the external test cohort consisted of 75 patients from another center. In the internal test cohort, the area under the curve was 0.813 (95% CI, 0.670-0.933) and in the external test cohort the area under the curve was 0.812 (95% CI, 0.606-0.956). The area under the curve was significantly higher than that of other ensemble learning models, logistic regression model, and European System for Cardiac Operative Risk Evaluation II (all, P<0.01). This model was used to develop an online, open-access calculator (http://42.240.140.58:1808/). Conclusions We constructed and validated an accurate and robust machine learning-based risk model to predict early mortality after surgery for infective endocarditis, which may help clinical decision-making and improve outcomes.

Belumosudil, ROCK2-specific inhibitor, alleviates cardiac fibrosis by inhibiting cardiac fibroblasts activation.

Cardiac fibrosis is thought to be the hallmark of pathological hypertrophic remodeling, of which the myofibroblast transdifferentiation is the key cell biological event. However, there is still no specific and effective therapeutic agent approved for cardiac fibrosis. To investigate the effects of belumosudil, the first ρ-associated kinase-2 (ROCK2)-specific inhibitor, on cardiac hypertrophy, fibrosis, and dysfunction induced by pressure overload, the transverse aortic constriction (TAC) or sham operation was carried out on wild-type C57BL/6 mice (male, 6-8 wk old) under pentobarbital anesthesia. After that, mice were randomly divided into three groups: sham operation + vehicle, TAC + vehicle, TAC + 50 mg·kg-1·day-1 belumosudil. We found that belumosudil effectively ameliorated cardiac hypertrophy, fibrosis, and dysfunction in TAC mice. To elucidate the underlying mechanism, we inhibited the expression of ROCK2 in vitro by either belumosudil or siRNA. We showed that the inhibition of ROCK2 by either belumosudil or knockdown suppressed cardiac fibroblasts activation and proliferation significantly induced by transforming growth factor-ß1 (TGF-ß1). Furthermore, our study confirmed ROCK2 mediates cardiac fibrosis by interacting with TGF-ß1/mothers against decapentaplegic homolog 2 (Smad2) pathway. Taken together, we demonstrated that belumosudil ameliorates cardiac hypertrophy and fibrosis induced by TAC via inhibiting cardiac fibroblasts activation. In conclusion, belumosudil may be a promising therapeutic drug for cardiac hypertrophy and fibrosis induced by myocardial pressure overload.NEW & NOTEWORTHY Although ρ-associated kinase-2 (ROCK2) is the main isoform of ρ-associated kinases (ROCKs) in the heart and more important in cardiac hypertrophy and fibrosis than ρ-associated kinase-1 (ROCK1), there has not been any pharmacological approach to inhibit ROCK2 selectively. Our study demonstrates for the first time that belumosudil, the first ROCK2-specific inhibitor, effectively ameliorates cardiac hypertrophy, fibrosis, and dysfunction induced by TAC via inhibiting cardiac fibroblasts activation.

Abnormal Liver Function Tests Were Related to Short- and Long-Term Prognosis in Critically Ill Patients With Primary Pulmonary Hypertension.

Aim: The aim of this study was to examine the utility of liver function tests (LFTs) in predicting the prognosis of critically ill patients with primary pulmonary hypertension (PPH) with/without liver disease. Methods: We retrieved the Medical Information Mart for Intensive Care III (MIMIC-III) database to acquire clinical data. From the database, we recruited adult patients that were equal to or older than 18 years with primary pulmonary hypertension (PPH) discharge from intensive care unit (ICU). Then, the relationship between LFTs and duration of hospitalization and ICU stays was examined based on the Spearman correlation. The chi-square assessment was conducted to examine the correlation between LFTs and death rates. Survival curves were plotted with the aid of the Kaplan-Meier technique, and the curves were subsequently compared utilizing the log-rank test. The LFTs were identified as independent predictive variables of death according to the results of multivariable logistic regression. The specificity and sensitivity for mortality were calculated utilizing receiver operating characteristic (ROC) curves and the area under the curve (AUC). Results: In total, 198 patients satisfying the inclusion criteria were recruited, among which there were 23 patients with liver disease. Only ALB was correlated with the length of ICU stay in the total PPH group. ALB independently served as a risk variable for hospital mortality and 90-day mortality and was significantly associated with 90-day and 4-year survival rates in both total PPH and PPH without liver disease. AST was correlated with hospital mortality and 90-day survival curves in both total PPH and PPH without liver disease and independently served as a risk factor for hospital and 90-day mortality only in the total PPH group. ALT independently acted as a risk variable for hospital mortality and total bilirubin was correlated with hospital mortality in the total group. The diagnostic performance of the predictive model combining the LFTs was moderately good for the hospital, 90-day, and 4-year mortality. Both Modeli End-Stage iLiveri Disease (MELD) score and albumin-bilirubin (ALBI) score were independent risk factors for short- and long-term prognosis. And they were also significantly associated with short- and long-term prognosis. Conclusion: Among critically ill patients with PPH and with or without liver illness, aberrant LFT was linked to short- and long-term prognoses.

Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat.

Introduction: Current targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of traditional Chinese medicine Qiang-Huo (Notopterygium incisum), had shown the antiproliferative and anti-inflammatory properties in previous studies, we hypothesized that it could play a role in ameliorating PAH. Methods: In vivo, we conducted monocrotaline (MCT) induced PAH rats and treated them with notopterol for 3 weeks. Then, the rats were examined by echocardiography and RV catheterization. The heart and lung specimens were harvested for the detection of gross examination, histological examination and expression of inflammatory molecules. In vitro, human pulmonary arterial smooth muscle cells (HPASMCs) were treated with notopterol after hypoxia; then, cell proliferation was assessed by cell counting kit-8 and Edu assay, and cell migration was detected by wound healing assays. Results: We found that notopterol improved mortality rate and RV function while reducing right ventricular systolic pressure in MCT-induced PAH rats. Furthermore, notopterol reduced right ventricular hypertrophy and fibrosis, and it also eased pulmonary vascular remodeling and MCT-induced muscularization. In addition, notopterol attenuated the pro-inflammatory factor (IL-1ß, IL-6) and PCNA in the lungs of PAH rats. For the cultured HPASMCs subjected to hypoxia, we found that notopterol can inhibit the proliferation and migration of HPASMCs. Conclusion: Our studies show that notopterol exerts anti-inflammatory and anti-proliferative effects in the pulmonary arteries, which may contribute to prevention of PAH.

Disheveled binding antagonist of ß-catenin 1 interacted with ß-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.

Previously, we demonstrated that the disheveled binding antagonist of ß-catenin 1 (DACT1) was involved in atrial fibrillation by regulating the reorganization of connexin 43 and ß-catenin in cardiomyocytes. Little is known, however, about DACT1 in human normal myocardial cells. Therefore, we used cardiomyocytes (CMs) derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to investigate the role of DACT1 and its connection with ß-catenin and connexin 43. While the ESC-CMs and iPSC-CMs were differentiated using commercial differentiation kits, the cardiac-specific markers were detected by immunofluorescence. The expression level of DACT1 was detected using western blotting, whereas the interaction of DACT1 and connexin 43 or ß-catenin was detected by immunofluorescence and co-immunoprecipitation (co-IP) assays. Both H1-CMs and SF-CMs were immunostained for cardiac-specific markers, including Troponin I, Troponin T, α-actinin, NKX2.5, and GATA6. While DACT1 was not expressed in both H1 ESCs and SF-iPSCs, it was, however, highly expressed in differentiated CMs, being also localized in the cytoplasm and the nucleus of differentiated CMs. Interestingly, the DACT1 expression in different nuclei was different in the same multinucleated cell. Moreover, DACT1 colocalized with ß-catenin in both the cytoplasm and nucleus of differentiated CMs, and it also colocalized with connexin 43 in the perinuclear region and the gap junctions of differentiated CMs. Co-IP results showed that DACT1 could directly bind to ß-catenin and connexin 43. Taken together, DACT1 interacted with ß-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.

Postoperative Serum Creatinine Serves as a Prognostic Predictor of Cardiac Surgery Patients.

BACKGROUND: Serum creatinine, an important diagnostic indicator for acute kidney injury (AKI), was considered to be a risk factor for cardiovascular disease. This study aimed to investigate the significance of postoperative serum creatinine in predicting the prognosis of cardiac surgery patients. METHODS: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to extract the clinical data. Adult (≥18 years) cardiac surgery patients in the database were enrolled. The correlation of postoperative serum creatinine with lengths of intensive care unit (ICU) stay was analyzed with Spearman correlation, and the association of postoperative serum creatinine with hospital mortality was analyzed with chi-square tests. Multivariable logistic regression was used to identify postoperative serum creatinine as an independent prognostic factor for hospital mortality. RESULTS: A total of 6,001 patients were enrolled in our study, among whom, 108 patients (1.8%) died in the hospital. Non-survivors had much higher postoperative serum creatinine levels (initial: 0.8 vs. 1.2 mg/dl, P < 0.001; maximum: 1.1 vs. 2.8 mg/dl, P < 0.001; minimum: 0.8 vs.1.1 mg/dl, P < 0.001). Positive correlations were observed between postoperative serum creatinine (P < 0.001) and lengths of ICU stay. For all models, postoperative initial creatinine, postoperative maximum creatinine, and postoperative minimum creatinine were all positively associated with hospital mortality (all P < 0.001). The predictive performance of postoperative serum creatinine was moderately good (area under the curve (AUC) for initial creatinine = 0.7583; AUC for maximum creatinine = 0.8413; AUC for minimum creatinine = 0.7063). CONCLUSIONS: This study demonstrated the potential to use postcardiac surgery serum creatinine as an outcome indicator.