Associations of 50 modifiable risk factors with atrial fibrillation using Mendelian randomization analysis.

BACKGROUND: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF. METHODS: Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses. RESULTS: Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist-hip ratio, central and peripheral fat/fat-free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity-related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF. CONCLUSIONS: This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention.

Comparison of human leukocyte antigen in patients with paroxysmal nocturnal hemoglobinuria of different clone sizes.

Glycosylphosphatidylinositol-anchored protein-deficient hematopoietic stem and progenitor cell development caused by PIGA mutations cannot fully explain the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH). Herein, patients newly diagnosed with PNH at our hospital between April 2019 and April 2021 were recruited. The human leukocyte antigen (HLA) class I and II loci were analyzed, and patients were stratified by PNH clone sizes: small (< 50%) and large (≥ 50%). In 40 patients (29 males; 72.5%), the median PNH clone size was 72%. Thirteen (32.5%) and twenty-seven (67.5%) patients harbored small and large PNH clones, respectively. DRB1*15:01 and DQB1*06:02 had higher frequencies in patients with PNH than in healthy controls (adjusted P-value = 4.10 × 10-4 and 4.10 × 10-4, respectively). Whole HLA class I and II allele contributions differed (P = 0.046 and 0.065, not significant difference) when comparing patients with small and large PNH clones. B*13:01 and C*04:01 allelic frequencies were significantly higher in patients with small clones (P = 0.032 and P = 0.032, respectively). Patients with small clones had higher class II HLA evolutionary divergence (HED) (P = 0.041) and global class I and II HED (P = 0.019). In the entire cohort, 17 HLA aberrations were found in 11 (27.5%) patients. No significant differences in HLA aberrations were found between patients with small or large clones. In conclusion, patients with small clones tended to have a higher frequency of immune attack-associated alleles. A higher HED in patients with small clones may reflect a propensity for T cell-mediated autoimmunity. HLA aberrations were similar between patients with small and large clones.

Association of stress hyperglycemia ratio and mortality in patients with sepsis: results from 13,199 patients.

BACKGROUND: The stress hyperglycemia ratio (SHR), adjusted for average glycemic status, is suggested for assessing actual blood glucose levels. Its link with adverse outcomes is known in certain populations, yet its impact on sepsis patients' prognosis is unclear. This study explores the association between SHR and mortality in sepsis. METHODS: We included 13,199 sepsis patients in this study and categorized SHR into distinct groups. Additionally, we utilized restricted cubic spline analysis to evaluate the correlation between SHR as a continuous variable and mortality. The primary outcome was 1-year all-cause mortality. Logistic regression and Cox proportional hazards models were employed to assess the associations between the SHR and both in-hospital mortality and 1-year mortality, respectively. RESULTS: Among the study participants, 4,690 (35.5%) patients died during the 1-year follow-up. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and 1-year mortality. Using an SHR of 0.99 as the reference point, the hazard ratio for predicted 1-year mortality increased by 1.17 (95% CI 1.08 to 1.27) per standard deviation above 0.99, whereas each standard deviation increase predicted the hazard ratio of 0.52 (95% CI 0.39 to 0.69) below 0.99. Furthermore, we found that SHR could enhance the predictive performance of conventional severity scores. CONCLUSION: There exists a U shaped association between SHR and mortality in sepsis patients, where both low and high SHR values are associated with an increased risk of poor outcomes.

Prognostic value of high-sensitivity C-reactive protein in patients undergoing percutaneous coronary intervention with different glycemic metabolism status.

BACKGROUND: High-sensitivity C-reaction protein (hsCRP), a biomarker of residual inflammatory risk, has been demonstrated with poor cardiovascular outcomes. We aimed to investigate the prognostic value of hsCRP in patients undergoing percutaneous coronary intervention (PCI) with or without diabetes mellitus (DM). METHODS: In this large-scale, prospective cohort study, we enrolled 8050 consecutive patients who underwent PCI for coronary artery stenosis. All subjects were stratified as high hsCRP (> 3 mg/L) and low hsCRP (≤ 3 mg/L) and were divided into four groups (hsCRP-L/non-DM, hsCRP-H/non-DM, hsCRP-L/DM, hsCRP-H/DM). The primary endpoint of the study was major adverse cardiovascular events (MACEs), including all-cause mortality, myocardial infarction, stroke, and unplanned vessel revascularization, evaluated at a 3 year follow-up. RESULTS: After 35.7 months (interquartile range: 33.2 to 36.0 months) of median follow-up time, 674 patients suffered from MACEs. We found elevated hsCRP was highly associated with an increased risk of MACEs in both diabetic (hazard ratio [HR] = 1.68, 95% confidence interval CI 1.29-2.19, P < 0.001) and non-diabetic patients (HR = 1.31, 95% CI: 1.05-1.62, P = 0.007) after adjustment for other confounding factors. Kaplan-Meier survival analysis showed the highest incidence of MACEs in hsCRP-H/DM (P < 0.001). In addition, the results of the restricted cubic spline analysis suggested a positive linear relationship between hsCRP and MACEs. CONCLUSION: Elevated hsCRP is an independent risk factors of MACEs in patients undergoing PCI irrespective of glycemic metabolism status.

Prognostic significance of the stress hyperglycemia ratio in critically ill patients.

BACKGROUND: The stress hyperglycemia ratio (SHR) has demonstrated a noteworthy association with unfavorable cardiovascular clinical outcomes and heightened in-hospital mortality. Nonetheless, this relationship in critically ill patients remains uncertain. This study aims to elucidate the correlation between SHR and patient prognosis within the critical care setting. METHODS: A total of 8978 patients admitted in intensive care unit (ICU) were included in this study. We categorized SHR into uniform groups and assessed its relationship with mortality using logistic or Cox regression analysis. Additionally, we employed the restricted cubic spline (RCS) analysis method to further evaluate the correlation between SHR as a continuous variable and mortality. The outcomes of interest in this study were in-hospital and 1-year all-cause mortality. RESULTS: In this investigation, a total of 825 (9.2%) patients experienced in-hospital mortality, while 3,130 (34.9%) individuals died within the 1-year follow-up period. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and both in-hospital and 1-year mortality. Specifically, within the SHR range of 0.75-0.99, the incidence of adverse events was minimized. For each 0.25 increase in the SHR level within this range, the risk of in-hospital mortality rose by 1.34-fold (odds ratio [OR]: 1.34, 95% CI: 1.25-1.44), while a 0.25 decrease in SHR within 0.75-0.99 range increased risk by 1.38-fold (OR: 1.38, 95% CI: 1.10-1.75). CONCLUSION: There was a U-shaped association between SHR and short- and long-term mortality in critical ill patients, and the inflection point of SHR for poor prognosis was identified at an SHR value of 0.96.

Treatment of refractory or relapsed myelodysplastic neoplasms with luspatercept: a multicenter Chinese study.

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67 years: range 29 to 80 years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9 weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8 weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84 g/L, and patients had significantly higher hemoglobin concentrations after 12 weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500 IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

Outcomes of catheter ablation in high-risk patients with Brugada syndrome refusing an implantable cardioverter defibrillator implantation.

AIMS: The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation. METHODS AND RESULTS: A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation-triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5-73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012). CONCLUSION: Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population.

The causal associations of non-alcoholic fatty liver disease with blood pressure and the mediating effects of cardiometabolic risk factors: A Mendelian randomization study.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is prevalent in hypertensive people, but the causal effect remains unclear. We employed Mendelian randomization (MR) approach to assess the causality between NAFLD and different blood pressure (BP) parameters. METHOD AND RESULTS: Instrumental variables for genetically predicted NAFLD, including chronically elevated serum alanine aminotransferase levels (cALT) and imaging and biopsy-confirmed NAFLD, were obtained from a genome-wide association study (N = 164,197). Multiple MR methods were implemented, including Inverse variance weighted, MR-Egger, Maximum likelihood, Weighted median, Simple median, Penalised weighted median, MR-RAPS, and cML-MA. Outliers were detected using MR-PRESSO, and pleiotropy was assessed using MR-Egger intercept and Phenoscanner. Heterogeneity was quantified using Cochran's Q and Rucker's Q' tests. Potential shared risk factors were analyzed to reveal the mediating effect. A higher genetic predisposition to cALT was causally associated with an increased risk of elevated BP levels, resulting in 0.65 mmHg (95% CI, 0.42-0.87), 0.38 mmHg (95% CI, 0.25-0.50) and 0.33 mmHg (95% CI, 0.22-0.44) higher for systolic BP, diastolic BP and pulse pressure, respectively. When more stringent criteria were used, imaging and biopsy-confirmed NAFLD showed a 1.12 mmHg (95% CI, 0.94-1.30) increase in SBP and a 0.55 mmHg (95% CI, 0.39-0.70) increase in DBP. Risk factor and mediation analyses suggested type 2 diabetes and fasting insulin levels might mediate the causal relationship between NAFLD and BP. CONCLUSION: The two-sample MR analyses showed robust causal effects of genetically predicted NAFLD on 3 different BP indices. The shared genetic profile between NAFLD and BP may suggest important therapeutic targets and early interventions for cardiometabolic risk factors.

Development and Validation of Machine Learning-Based Models to Predict In-Hospital Mortality in Life-Threatening Ventricular Arrhythmias: Retrospective Cohort Study.

BACKGROUND: Life-threatening ventricular arrhythmias (LTVAs) are main causes of sudden cardiac arrest and are highly associated with an increased risk of mortality. A prediction model that enables early identification of the high-risk individuals is still lacking. OBJECTIVE: We aimed to build machine learning (ML)-based models to predict in-hospital mortality in patients with LTVA. METHODS: A total of 3140 patients with LTVA were randomly divided into training (n=2512, 80%) and internal validation (n=628, 20%) sets. Moreover, data of 2851 patients from another database were collected as the external validation set. The primary output was the probability of in-hospital mortality. The discriminatory ability was evaluated by the area under the receiver operating characteristic curve (AUC). The prediction performances of 5 ML algorithms were compared with 2 conventional scoring systems, namely, the simplified acute physiology score (SAPS-II) and the logistic organ dysfunction system (LODS). RESULTS: The prediction performance of the 5 ML algorithms significantly outperformed the traditional models in predicting in-hospital mortality. CatBoost showed the highest AUC of 90.5% (95% CI 87.5%-93.5%), followed by LightGBM with an AUC of 90.1% (95% CI 86.8%-93.4%). Conversely, the predictive values of SAPS-II and LODS were unsatisfactory, with AUCs of 78.0% (95% CI 71.7%-84.3%) and 74.9% (95% CI 67.2%-82.6%), respectively. The superiority of ML-based models was also shown in the external validation set. CONCLUSIONS: ML-based models could improve the predictive values of in-hospital mortality prediction for patients with LTVA compared with traditional scoring systems.

Analysis of and Experimental Research on a Hydraulic Traction System Based on a Digital Hydraulic Transformer.

In this study, we designed a new type of digital hydraulic transformer using four gear-pump/motor units with a displacement ratio of 20:21:22:23 and two control valve groups that consist of four solenoid directional valves. The driving gear shafts of the four gear-pump/motor units are fixedly connected to achieve synchronous rotation. The two control valve groups are respectively installed through an integrated valve block on the inlet and outlet of each gear-pump/motor unit. With the objective of reducing the installed power and energy consumption of hydraulic traction systems, we propose a new energy-saving hydraulic system based on a digital hydraulic transformer. This hydraulic system uses a digital hydraulic transformer as a pressure/flow control element. By controlling the power on/off states of eight solenoid directional valves, the digital hydraulic transformer can realize a change in output flow and then a change in speed of the hydraulic cylinder piston rod. Through the theoretical derivation and simulation analysis of the hydraulic system pressure/flow change process, and the experimental verification of the built hydraulic traction system based on the experimental platform, a conclusion is drawn that the proposed digital hydraulic transformer can change the output pressure/flow of a hydraulic system through a binary digital control, verifying the feasibility of the pressure change principle of the designed digital hydraulic transformer and the rationality of the hydraulic traction system circuit.

Research on Shipborne Helicopter Electric Rapid Secure Device: System Design, Modeling, and Simulation.

The research objective of this paper is to propose a new type of ERSD to solve the problem of the uncontrollable velocity of the claw in the current RSD. Firstly, the working characteristics of the RSD in ASIST are analyzed, and the design scheme of the transmission system of the ERSD is provided. The control system is designed by combining the vector control algorithm with the fuzzy adaptive PID control algorithm. On this basis, the trajectory planning of claw capture velocity is completed. Finally, the dynamics model of the transmission system of the ERSD is built by power bond graph theory, and the system simulation is carried out. The results show that the maximum capture time, velocity, and force were reduced by 47%, 53%, and 80%. In addition, when the ERSD is towing the helicopter, the mechanical claw can still provide good velocity tracking performance under a maximum interference load of 34,000 N.

Active Disturbance Rejection Position Synchronous Control of Dual-Hydraulic Actuators with Unknown Dead-Zones.

In this paper, an integrated control strategy of position synchronization control for dual-electro-hydraulic actuators with unknown dead-zones is proposed. The unified control scheme consists of two parts: One is adaptive dead-zone inverse controllers of each hydraulic actuator to offset the unknown dead-zones. The other is the linear active disturbance rejection controller (LADRC) for position synchronization error. First, the model of the electro-hydraulic proportional position control system (EPPS) was identified by the forgetting factor recursive least square (FFRLS) algorithm. Next, the model reference dead-zone inverse adaptive controller (MRDIAC) was developed to compensate for the delay of actuator response caused by unknown proportional valve dead-zones. Meanwhile, the validity of the adaptive law was proven by the Lyapunov theory. Therefore, the position control accuracy of each hydraulic actuator is guaranteed. Besides, to improve the precision of position synchronization control of dual-hydraulic actuators, a simple and elegant synchronous error-based LADRC was adopted, which applies the total disturbances design concept to eliminate and compensate for motion coupling rather than cross-coupling technology. The performance of the proposed control solution was investigated through extensive comparative experiments based on a hydraulic test platform. The experimental results successfully demonstrate the effectiveness and practicality of the proposed method.

Design, synthesis and biological evaluation of six dinuclear platinum(II) complexes.

Six dinuclear platinum(II) complexes with a chiral tetradentate ligand, (1R,1'R,2R,2'R)-N1,N1'-(1,4-phenylenebis(methylene))dicyclohexane-1,2-diamine, have been designed, synthesized and characterized. In vitro cytotoxicity evaluation of these metal complexes against human A549, HCT-116, MCF-7 and HepG-2 cell lines have been carried out. All compounds showed antitumor activity to HepG-2, HCT-116 and A549. Particularly, compounds A1 and A2 exhibited significant better activity than other four compounds and A2 even showed comparable cytotoxicity to cisplatin against HepG-2 cell line.

Clinical Decision Support Requirements for Ventricular Tachycardia Diagnosis Within the Frameworks of Knowledge and Practice: Survey Study.

BACKGROUND: Ventricular tachycardia (VT) diagnosis is challenging due to the similarity between VT and some forms of supraventricular tachycardia, complexity of clinical manifestations, heterogeneity of underlying diseases, and potential for life-threatening hemodynamic instability. Clinical decision support systems (CDSSs) have emerged as promising tools to augment the diagnostic capabilities of cardiologists. However, a requirements analysis is acknowledged to be vital for the success of a CDSS, especially for complex clinical tasks such as VT diagnosis. OBJECTIVE: The aims of this study were to analyze the requirements for a VT diagnosis CDSS within the frameworks of knowledge and practice and to determine the clinical decision support (CDS) needs. METHODS: Our multidisciplinary team first conducted semistructured interviews with seven cardiologists related to the clinical challenges of VT and expected decision support. A questionnaire was designed by the multidisciplinary team based on the results of interviews. The questionnaire was divided into four sections: demographic information, knowledge assessment, practice assessment, and CDS needs. The practice section consisted of two simulated cases for a total score of 10 marks. Online questionnaires were disseminated to registered cardiologists across China from December 2022 to February 2023. The scores for the practice section were summarized as continuous variables, using the mean, median, and range. The knowledge and CDS needs sections were assessed using a 4-point Likert scale without a neutral option. Kruskal-Wallis tests were performed to investigate the relationship between scores and practice years or specialty. RESULTS: Of the 687 cardiologists who completed the questionnaire, 567 responses were eligible for further analysis. The results of the knowledge assessment showed that 383 cardiologists (68%) lacked knowledge in diagnostic evaluation. The overall average score of the practice assessment was 6.11 (SD 0.55); the etiological diagnosis section had the highest overall scores (mean 6.74, SD 1.75), whereas the diagnostic evaluation section had the lowest scores (mean 5.78, SD 1.19). A majority of cardiologists (344/567, 60.7%) reported the need for a CDSS. There was a significant difference in practice competency scores between general cardiologists and arrhythmia specialists (P=.02). CONCLUSIONS: There was a notable deficiency in the knowledge and practice of VT among Chinese cardiologists. Specific knowledge and practice support requirements were identified, which provide a foundation for further development and optimization of a CDSS. Moreover, it is important to consider clinicians' specialization levels and years of practice for effective and personalized support.

Electrocardiographic tracking of left ventricular hypertrophy in hypertension: incidence and prognostic outcomes from the SPRINT trial.

BACKGROUND: This study explores the impact of intensive blood pressure (BP) control on left ventricular hypertrophy (LVH) incidence and evaluates the prognostic implications of LVH status (pre-existing/new-onset/persistent/regression) using Systolic Blood Pressure Intervention Trial (SPRINT) Electrocardiogram Data. METHODS: Poisson regression was used to assess new-onset LVH and LVH regression rates. Multivariable-adjusted Cox proportional hazard models determined the risk of adverse cardiovascular events (ACE), a composite of myocardial infarction (MI), non-MI acute coronary syndrome, stroke, heart failure, or cardiovascular death, alongside safety adverse events. RESULTS: In 8,016 participants, intensive BP control significantly reduced new-onset LVH (8.27 vs. 14.79 per 1000-person years; adjusted p<0.001) and increased LVH regression (14.89 vs. 11.89 per 1000-person years; adjusted p<0.001). Elevated ACE risk was notable in participants with pre-existing LVH [adjusted HR: 1.94 (95% CI: 1.25-2.99); p = 0.003], new-onset LVH [adjusted 1.74 (95% CI: 1.16-2.60); p = 0.007], and persistent LVH[adjusted HR: 1.96 (95% CI: 1.11-3.46); p = 0.020], compared to those without LVH. Intriguingly, LVH regression attenuated this risk increment [adjusted HR: 1.57 (95% CI: 0.98-2.53); p = 0.062]. Achieving a BP target of < 120/80 mmHg nullified the increased ACE risk in those with pre-existing LVH. CONCLUSIONS: Intensive BP control is instrumental in both reducing the emergence of LVH and fostering its regression. Pre-existing, new-onset LVH and persistent LV remain a predictor of adverse cardiovascular prognosis, whereas LVH regression and achieving on-treatment BP < 120/80 mmHg in pre-existing LVH individuals may further mitigate residual cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov Unique Identifier: NCT01206062.

Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope.

BACKGROUND: Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce. METHODS: This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed. RESULTS: After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype (P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure (n = 6, 16.7%), followed by mixed (n = 26, 30.6%) and vasodepressive (n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve (P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type (P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC ≥ 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02). CONCLUSIONS: Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC ≥ 8.4 ms might benefit from CNA.

U-shaped association between stress hyperglycemia ratio and risk of all-cause mortality in cardiac ICU.

BACKGROUND: Stress hyperglycemia has been associated with poor prognosis in patients admitted to the cardiac intensive care unit (ICU). Recently, the stress hyperglycemia ratio (SHR) has been proposed to reflect true acute hyperglycemic. This study aimed to investigate the relationship between SHR and prognosis of patients in the cardiac ICU. METHODS: A retrospective analysis was conducted on a cohort of 5,564 patients admitted to the cardiac ICU. The participants were divided into seven groups based on their SHR levels. SHR was calculated as admission blood glucose/[(28.7 × HbA1c %) - 46.7]. The primary outcomes of this study were 28-day all-cause mortality. RESULTS: During the follow-up period, 349 (6.3%) patients succumbed within 28 days. A U-shaped correlation between SHR and mortality persisted, even after adjusting for other confounding variables, with a discernible inflection point at 0.95. When SHR surpassed 0.95, each standard deviation (SD) increase corresponded to a 1.41-fold elevation in the risk of mortality (odds ratio [OR]: 1.41, 95% CI: 1.25 to 1.59). In contrast, when SHR fell below 0.95, each SD increment correlated with a significantly reduced risk of mortality (OR: 0.56, 95% CI: 0.34 to 0.91). CONCLUSION: There was a U-shaped association between SHR and short -term mortality in patients in the cardiac ICU. The inflection point of SHR for poor prognosis was identified at an SHR value of 0.95.

Efficacy of catheter ablation for ventricular tachycardia in ischemic cardiomyopathy patients without an ICD implantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) prevents sudden cardiac death in patients with ischemic cardiomyopathy (ICM). Catheter ablation has been shown to effectively reduce ventricular tachycardia (VT) recurrence, yet its efficacy in patients without an ICD implantation remains uncertain. OBJECTIVE: We aimed to investigate the outcomes of ablation for VT in patients with ICM without a backup ICD. METHODS: Patients with ICM who received ablation for VT without an ICD implantation were included in this study. Ablation was guided by either activation mapping or substrate mapping. Endocardial ablation was the primary strategy; epicardial access was considered when endocardial ablation failed. The primary end point was VT recurrence during follow-up; secondary end points included cardiovascular rehospitalization, all-cause mortality, and a composite of these events. RESULTS: A total of 114 patients were included, with the mean age of 58.2 ± 11.1 years, 102 of whom (89.5%) were male. Twelve patients (10.5%) underwent endo-epicardial ablation, whereas the rest received endocardial ablation. With a median follow-up of 53.8 months (24.8-84.2 months), VT recurred in 45 patients (39.5%), and 6 patients (5.3%) died, including 2 sudden cardiac deaths. The recurrence rate of VT was significantly lower in patients undergoing endo-epicardial ablation than in those with endocardial ablation only (8.3% vs 43.1%; log-rank P = .032). After multivariate adjustment, epicardial ablation remained associated with a reduced risk of VT recurrence (hazard ratio, 0.14; 95% confidential interval, 0.02-0.98; P = .048). CONCLUSION: Patients with ICM undergoing VT ablation without a backup ICD experienced a notably low rate of arrhythmic death. Most recurrences proved nonlethal.

Lupeol alleviates autoimmune myocarditis by suppressing macrophage pyroptosis and polarization via PPARα/LACC1/NF-κB signaling pathway.

BACKGROUND: Autoimmune myocarditis, with increasing incidence and limited therapeutic strategies, is in urgent need to explore its underlying mechanisms and effective drugs. Pyroptosis is a programmed cell death that may contribute to the pathogenesis of myocarditis. Nonetheless, no direct evidence validated the role of pyroptosis in autoimmune myocarditis. Lupeol (Lup), a pentacyclic triterpene, possesses various biological activities such as antidiabetic properties. However, the effects of Lup on autoimmune myocarditis and pyroptosis remain unelucidated. PURPOSE: This study aimed to reveal the role of pyroptosis in autoimmune myocarditis and explore the protective effects of Lup, and its engaged mechanisms. METHODS: The experimental autoimmune myocarditis (EAM) mouse model was established by immunization with a fragment of cardiac myosin in Balb/c mice. Lup and MCC950 were administered after EAM induction. The protective effects were assessed by inflammation score, cardiac injury, chronic fibrosis, and cardiac function. Mechanistically, the effects of Lup on the M1 polarization and pyroptosis of macrophages were evaluated. Transcriptome sequencing and molecular docking were subsequently employed, and the underlying mechanisms of Lup were further explored in vitro with small interfering RNA and adenovirus. RESULTS: Administration of Lup and MCC950 alleviated EAM progression. Western blotting and immunofluorescence staining identified macrophages as the primary cells undergoing pyroptosis. Lup inhibited the expression of pyroptosis-associated proteins in macrophages during EAM in a dose-dependent manner. Furthermore, Lup suppressed pyroptosis in both bone marrow-derived macrophages (BMDMs) and THP-1-derived macrophages in vitro. In addition, Lup inhibited the M1 polarization of macrophages both in vivo and in vitro. Mechanistically, the protective effects of Lup were demonstrated via the suppression of the nuclear factor-κΒ (NF-κB) signaling pathway. Transcriptome sequencing and molecular docking revealed the potential involvement of peroxisome proliferator-associated receptor α (PPARα). Subsequently, we demonstrated that Lup activated PPARα to reduce the expression level of LACC1, thereby inhibiting the NF-κB pathway and pyroptosis. CONCLUSION: Our findings indicated the crucial role of macrophage pyroptosis in the pathogenesis of EAM. Lup ameliorated EAM by inhibiting the M1 polarization and pyroptosis of macrophages through the PPARα/LACC1/NF-κB signaling pathway. Thus, our results provided a novel therapeutic target and agent for myocarditis.

Parameter adaptive sliding mode trajectory tracking strategy with initial value identification for the swing in a hydraulic construction robot.

A novel trajectory tracking strategy is developed for a double actuated swing in a hydraulic construction robot. Specifically, a nonlinear hydraulic dynamics model of a double actuated swing is established, and a parameter adaptive sliding mode control strategy is designed to enhance the trajectory tracking performance. When an object is grabbed and unloaded, the moment of inertia of a swing considerably changes, and the performance of the estimation algorithm is generally inadequate. Thus, it is necessary to establish an algorithm to identify the initial value of the moment of inertia of the object. To this end, this paper proposes a novel initial value identification algorithm based on a two-DOF robot gravity force identification method combined with stereo vision information. The performance of the identification algorithm is enhanced. Simulations and experiments are performed to verify the effect of the novel control scheme.