Interpretable machine learning model for new-onset atrial fibrillation prediction in critically ill patients: a multi-center study.

BACKGROUND: New-onset atrial fibrillation (NOAF) is the most common arrhythmia in critically ill patients admitted to intensive care and is associated with poor prognosis and disease burden. Identifying high-risk individuals early is crucial. This study aims to create and validate a NOAF prediction model for critically ill patients using machine learning (ML). METHODS: The data came from two non-overlapping datasets from the Medical Information Mart for Intensive Care (MIMIC), with MIMIC-IV used for training and subset of MIMIC-III used as external validation. LASSO regression was used for feature selection. Eight ML algorithms were employed to construct the prediction model. Model performance was evaluated based on identification, calibration, and clinical application. The SHapley Additive exPlanations (SHAP) method was used for visualizing model characteristics and individual case predictions. RESULTS: Among 16,528 MIMIC-IV patients, 1520 (9.2%) developed AF post-ICU admission. A model with 23 variables was built, with XGBoost performing best, achieving an AUC of 0.891 (0.873-0.888) in validation and 0.769 (0.756-0.782) in external validation. Key predictors included age, mechanical ventilation, urine output, sepsis, blood urea nitrogen, percutaneous arterial oxygen saturation, continuous renal replacement therapy and weight. A risk probability greater than 0.6 was defined as high risk. A friendly user interface had been developed for clinician use. CONCLUSION: We developed a ML model to predict the risk of NOAF in critically ill patients without cardiac surgery and validated its potential as a clinically reliable tool. SHAP improves the interpretability of the model, enables clinicians to better understand the causes of NOAF, helps clinicians to prevent it in advance and improves patient outcomes.

Genetically predicted hypothyroidism, thyroid hormone treatment, and the risk of cardiovascular diseases: a mendelian randomization study.

BACKGROUND: In this study, we explored the impact of hypothyroidism and thyroid hormone replacement therapy on the risk of developing cardiovascular diseases, including myocardial infarction, heart failure, and cardiac death, via Mendelian randomization analysis. METHODS: Genetic instrumental variables related to hypothyroidism, levothyroxine treatment (refer to Participants were taking the medication levothyroxine sodium) and adverse cardiovascular events were obtained from a large publicly available genome-wide association study. Two-sample Mendelian randomization analysis was performed via inverse-variance weighting as the primary method. To ensure the reliability of our findings, we performed MR‒Egger regression, Cochran's Q statistic, and leave-one-out analysis. Additionally, multivariable Mendelian randomization was employed to regulate confounding factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), diabetes, cholesterol, low-density lipoprotein (LDL), triglycerides and metformin. A mediation analysis was conducted to assess the mediating effects on the association between exposure and outcome by treating atrial fibrillation and stroke as mediator variables of levothyroxine treatment and bradycardia as mediator variables of hypothyroidism. RESULTS: Genetically predicted hypothyroidism and levothyroxine treatment were significantly associated with the risk of experiencing myocardial infarction [levothyroxine: odds ratio (OR) 3.75, 95% confidence interval (CI): 1.80-7.80; hypothyroidism: OR: 15.11, 95% CI: 2.93-77.88]. Levothyroxine treatment was also significantly related to the risk of experiencing heart failure (OR: 2.16, 95% CI: 1.21-3.88). However, no associations were detected between hypothyroidism and the risk of experiencing heart failure or between hypothyroidism or levothyroxine treatment and the risk of experiencing cardiac death. After adjusting for confounding factors, the results remained stable. Additionally, mediation analysis indicated that atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction. CONCLUSION: The results of our study suggest a positive association between hypothyroidism and myocardial infarction and highlight the potential effects of levothyroxine treatment, the main thyroid hormone replacement therapy approach, on increasing the risk of experiencing myocardial infarction and heart failure.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Formation control of fixed-wing UAVs with communication delay.

Fixed-wing unmanned aerial vehicles (UAVs) possess high speed and non-hovering capabilities, rendering them uniquely advantages for reconnaissance and detection. The focus of this paper is to addressing the problem of formation control for fixed-wing UAVs in the presence of communication delay. To tackle this problem, for the non-holonomic kinematic model, we propose an intuitive and practical control law based on the leader-follower method to ensure that UAVs maintain a predetermined geometric formation. The stability analysis of the system with communication delay is conducted by constructing a strict Lyapunov-Krasovskii function. Furthermore, we consider the impact of communication delay on formation accuracy and present a prediction algorithm capable of forecasting the actual position of each UAV. To validate our theoretical findings, both digital simulation and hardware-in-loop experiment are conducted.

Lead I R-wave indexes: A novel electrocardiographic criterion for distinguishing the origin of idiopathic premature ventricular contractions from the three subregions of the aortic sinus cusps.

PURPOSE: The current study was conducted to investigate the electrocardiographic (ECG) characteristics of idiopathic premature ventricular contractions (PVCs) originating from the aortic sinus cusp (ASC) and establish a novel ECG criterion to discriminate PVCs originating from the right coronary cusp (RCC), left coronary cusp (LCC), and the left and right coronary cusp junction (LRJ). METHODS: A retrospective analysis was performed on a total of 133 patients with idiopathic PVCs who underwent successful mapping and ablation. The sites of origin (SOO) were confirmed using fluoroscopy and a three-dimensional mapping system during radiofrequency catheter ablation (RFCA). Among the patients, 69 had PVCs originating from the LCC, 39 from the RCC, and 25 from the LRJ. Characteristics of surface 12­lead electrocardiograms (ECGs) recorded during PVCs were analyzed. Q-, R-, S, and R'-wave amplitudes were measured in lead I, and the lead I R-wave indexes (IRa, IRb, IRc, IRd, and IRe) were derived by employing multiplication, subtraction, sum, and division operations on these ECG measurements. Notably, IRb and IRe demonstrated usefulness as ECG indexes for discriminating PVCs originating from RCC, LCC, and LRJ in the ASC. RESULTS: The R- and S-wave amplitudes in lead I exhibited statistically significant differences among the three groups (P < 0.001 and P < 0.001, respectively). In discriminating PVCs originating from the RCC from the other two groups, IRb showed the largest area under the curve (AUC) of 0.813, as assessed by receiver operating characteristic (ROC) analysis, with a cutoff value of ≤0.5 indicating PVCs of RCC origin. The sensitivity and specificity were 80.3% and 78.7%, respectively. For discriminating PVCs arising from the LCC from those in the LRJ group, IRe exhibited the largest AUC of 0.801, with an optimal cutoff value of 0. An IRe value >0 indicated PVCs originating from the LRJ, while an IRe value ≤0 indicated PVCs originating from the LCC. The sensitivity and specificity of the IRe index were 84.0% and 70.7%, respectively. CONCLUSION: Lead I R-wave indexes provided simple and useful ECG criteria for discriminating PVCs originating from the LCC, RCC, and LRJ in the left ventricular outflow tract (LVOT).

Global cardiovascular diseases burden attributable to high sodium intake from 1990 to 2019.

Sodium intake shows a positive correlation with blood pressure, resulting in an increased risk for cardiovascular diseases (CVD). Salt reduction is a key step toward the WHO's goal of 25% reduction in mortality from non-communicable diseases (NCDs) by 2025. This study aims to assess the current condition and temporal changes of the global CVD burden due to high sodium intake (HSI). We extracted data from the Global Burden of Disease (GBD) study 2019. The numbers and age-standardized rates of mortality and disability-adjusted life-years (DALYs), stratified by location, sex, and socio-demographic Index (SDI), were used to assess the high sodium intake attributable CVD burden from 1990 to 2019. The relationship between the DALYs rates and related factors was evaluated by stepwise multiple linear regression analysis. Globally, in 2019, the deaths and DALYs of HSI-related CVD were 1.72 million and 40.54 million, respectively, increasing by 41.08% and 33.06% from 1990. Meanwhile, the corresponding mortality and DALYs rates dropped by 35.1% and 35.2%, respectively. The high-middle and middle SDI quintiles bore almost two-thirds of CVD burden caused by HSI. And the leading cause of HSI attributable CVD burden was ischemic heart disease. Universal health coverage (UHC) was associated with the DALYs rates after adjustment. From 1990 to 2019, the global CVD burden attributable to HSI has declined with spatiotemporal and sexual heterogeneity. However, it remains a major public health challenge because of the increasing absolute numbers. Improving UHC serves as an effective strategy to reduce the HSI-related CVD burden.

Different hydration methods for the prevention of contrast-induced nephropathy in patients with elective percutaneous coronary intervention: a retrospective study.

BACKGROUND: Hydration is currently the main measure to prevent contrast-induced nephropathy (CIN). We aimed to compare the preventive effect of preprocedure and postprocedure hydration on CIN in patients with coronary heart disease undergoing elective percutaneous coronary intervention (PCI). METHODS: A retrospective study included 198 cases of postprocedure hydration and 396 cases of preprocedure hydration using propensity score matching. The incidence of CIN 48 h after PCI and adverse events within 30 days after contrast media exposure were compared between the two groups. Logistic regression analysis was used to analyse the risk factors for CIN. RESULTS: The incidence of CIN in the postprocedure hydration group was 3.54%, while that in the preprocedure hydration group was 4.8%. There was no significant difference between the two groups (p = 0.478). Multivariate logistic regression analysis showed that diabetes mellitus, baseline BNP and cystatin C levels, and contrast agent dosage were independent risk factors for CIN. There was no significant difference in the incidence of major adverse events between the two groups (3.03% vs. 2.02%, p = 0.830). CONCLUSIONS: Postprocedure hydration is equally effective compared to preoperative hydration in the prevention of CIN in patients with coronary heart disease undergoing elective PCI.

Effects of Oral Inflammatory Diseases and Oral Hygiene on Atrial Fibrillation: A Systematic Review.

Objective: Research evidence suggests a link between periodontitis (PD) and atrial fibrillation, but the nature of this link is unclear. This study aimed to systematically review and evaluate the association between PD, other oral diseases, and atrial fibrillation and the role of oral hygiene in preventing atrial fibrillation. Methods: We searched the Medline, Embase, Cochrane Library, and Web of Science databases for the clinical study of oral health and atrial fibrillation from inception to November 2022. Oral health conditions included PD and other oral inflammatory diseases, regular oral hygiene, and tooth brushing. The primary outcomes were the risk of new-onset atrial fibrillation in patients with oral disease, the effect of regular oral care on preventing atrial fibrillation, the effect of frequent tooth brushing on preventing atrial fibrillation, and the incidence of atrial fibrillation in PD patients. Results: Eight clinical trials with a total of 4,328,355 patients were included. The result of the research showed that PD and other impaired oral health may be associated with new-onset atrial fibrillation, and its severity was dose-responsive to the risk of atrial fibrillation. The incidence of atrial fibrillation in patients with severe PD was about 16.3%. Moreover, PD may increase the risk of long-term arrhythmia in patients with atrial fibrillation. Regular oral care and frequent tooth brushing can reduce the incidence of atrial fibrillation. Conclusion: Regular and moderate oral hygiene, frequent tooth brushing, and prevention of PD and other oral inflammatory diseases could reduce the occurrence of atrial fibrillation. It is recommended to strengthen the popularization of oral health knowledge in the publicity related to atrial fibrillation.

MiR-4291 stabilized the vulnerable atherosclerotic plaques by degrading the MAPK1/ERK2 in ApoE-/- mice.

Background: This study sought to explore the mechanism of action of the micro ribonucleic acid (miR)-4291 in stabilizing atherosclerotic (AS) plaques. Methods: An AS model of apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (HFD) was established. Oxidized low-density lipoprotein (ox-LDL) was used to induce an inflammatory response of RAW264.7 macrophages. The mice were divided into the normal diet (ND) + miR-4291 negative control (NC) group, the ND + miR-4291 mimic group, the HFD + miR-4291 NC group, and the HFD + miR-4291 mimic group. They were also classified into the miR-4291 NC group, the miR-4291 mimic group, the ox-LDL + miR-4291 NC group, and the ox-LDL + miR-4291 mimic group. The arterial plaque burden of the mice was assessed by hematoxylin-eosin staining and immunohistochemistry, and the expression of phosphorylated-extracellular signal-regulated kinase 2 (p-ERK2) and related proteins in the arterial plaques and RAW264.7 macrophages of the mice were detected by Western blotting. Results: Obvious plaques with massive macrophage infiltration were found in the aortic roots of the mice fed a HFD, and smooth muscle cells were found at the margin of the plaques. In the HFD + miR-4291 mimic group, the number of plaques and macrophages was significantly declined, but there were no significant changes in the smooth muscle cells compared to those in the HFD + miR-4291 NC group. The Western blot results showed that miR-4291 reduced the protein expression of p-ERK1-2, t-ERK1-2, TNF-α, MCP-1, MMP-1, MMP-3, and MMP-9 in the AS plaques and the ox-LDL-induced RAW264.7 macrophages of the mice fed a HFD. Conclusions: MiR-4291 reduced the expression of MMP-2/9 by inhibiting the activity of ERK2, which in turn increased the fibrous cap thickness and stabilized the vulnerable plaques in AS.

Global burden of atrial fibrillation/flutter due to high systolic blood pressure from 1990 to 2019: estimates from the global burden of disease study 2019.

Atrial fibrillation/atrial flutter (AF/AFL) has progressed to be a public health concern, and high systolic blood pressure (HSBP) remains the leading risk factor for AF/AFL. This study estimated the HSBP attributable AF/AFL burden based on the data from the Global Burden of Disease (GBD) study 2019. Numbers, age-standardized rates (ASR) of deaths, disability-adjusted life years (DALYs), and corresponding estimated annual percentage change (EAPC) were analyzed by age, sex, sociodemographic index (SDI), and locations. Gini coefficient was calculated to evaluate health inequality. Globally, HSBP-related AF/AFL caused 107 091 deaths and 3 337 876 DALYs in 2019, an increase of 142.5% and 105.9% from 1990, respectively. The corresponding mortality and DALYs ASR declined by 5.8% and 7.7%. High-income Asia Pacific experienced the greatest decrease in mortality and DALYs ASR, whereas the largest increase was observed in Andean Latin America. Almost half of the HSBP-related AF/AFL burden was carried by high and high-middle SDI regions, and it was experiencing a shift to lower SDI regions. A negative correlation was detected between EAPC and SDI. Females and elderly people tended to have a higher AF/AFL burden, whereas young adults (30-49 years old) experienced an annual increase in AF/AFL burden. The Gini index of DALYs rate decreased from 0.224 in 1990 to 0.183 in 2019. Despite improved inequality having been observed over the past decades, the HSBP-related AF/AFL burden varied across regions, sexes, and ages. Cost-effective preventive, diagnostic, and therapeutic tools are required to be implemented in less developed regions.

The R-S difference index: A new electrocardiographic method for differentiating idiopathic premature ventricular contractions originating from the left and right ventricular outflow tracts presenting a left bundle branch block pattern.

Introduction: Differentiating idiopathic premature ventricular contractions (PVCs) originating from the right and left ventricular outflow tracts with a left bundle branch block (LBBB) morphology is relevant to catheter ablation planning and important for lowering the risk of complications. This study established a novel electrocardiographic (ECG) criterion to discriminate PVCs originating from the septum of the right ventricular outflow tract (s-RVOT) and those originating from the aortic sinus cusp of the left ventricular outflow tract (LVOT-ASC). Methods: A total of 259 patients with idiopathic PVCs originating from ventricular outflow tract with a LBBB pattern who underwent successful catheter ablation were retrospectively included. Among them, the PVCs originated from the s-RVOT in 183 patients and from the LVOT-ASC in 76 patients. The surface ECGs of the PVCs and sinus beats were analyzed using an electronic caliper. The R-S difference index in the precordial leads was calculated as V2R + V3R + V4R - V1S. Results: PVCs originating from both the s-RVOT and LVOT-ASC displayed an inferior axis (dominant R waves in leads II, III, and aVF). Compared with the s-RVOT group, the R-wave amplitudes on leads II, III, and aVF were significantly larger in the LVOT-ASC group (p < 0.001, p < 0.003, and p < 0.001, respectively). Compared to the LVOT-ASC group, the s-RVOT group showed smaller R-wave amplitudes on leads V1-V6 (p = 0.021, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively) and larger S-wave amplitudes on leads V1-V3 (p < 0.001, p < 0.001, and p < 0.001, respectively). Lead V3 was the most common transitional lead in both groups. Analysis of the receiver operating characteristic curve showed that the R-wave amplitude on lead V3 had the largest area under the curve (AUC) of 0.856 followed by the R-wave amplitudes on leads V4 (0.834) and V2 (0.806). The AUC of the R-S difference index was 0.867. An R-S difference index greater than 20.9 predicted an LVOT-ASC origin with 73.7% sensitivity and 86.3% specificity. This index is superior to previous criteria in differentiating PVCs with LBBB morphology and inferior axis originating from s-RVOT vs. LVOT-ASC. Conclusions: The R-S difference index in precordial leads is a useful new ECG criterion for distinguishing LVOT-PVCs from RVOT-PVCs with LBBB morphology.

Clinical Characteristics of Patients with Arrhythmias of the Idiopathic Outflow Tract Ventricular: Age, Gender, Comorbidities, Laboratory Test Results, and Echocardiographic Parameters.

Context: Idiopathic ventricular arrhythmias (IVAs) are a spectrum of ventricular arrhythmia (VA) without structural heart disease (SHD), that includes premature ventricular contractions (PVCs) and ventricular tachycardia (VT). The clinical characteristics of patients with PVCs or VT remain unclear, including distribution of the origin of arrhythmias, age and gender differences, comorbidities, laboratory tests, and electrocardiographic parameters. Objective: The study intended to compare the clinical characteristics of the right ventricular outflow tract (RVOT)- and left ventricular outflow tract (LVOT)-VT of a large group of consecutive patients, to investigate the distribution of the origin of the arrhythmias, age and gender differences, comorbidities, laboratory-examination results, and echocardiographic parameters. Methods: The research team designed a retrospective study to collect data on the above-mentioned variables. Setting: The study occurred at the Second Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 774 patients with symptomatic ventricular arrhythmias, 328 males and 446 females with the mean age of 48.6 ± 15.7 years, who underwent catheter ablation between January 2015 and January 2019. Participants were divided into the right ventricular outflow tract (RVOT) group and left ventricular outflow tract (LVOT) group, according to the different origins of their arrhythmias, with 428 participants in the RVOT group and 180 in the LVOT group. Outcome Measures: The research team collected and analyzed the data for the original sites of the IVAs; ages; genders; comorbidities; laboratory examinations, including routine blood tests, liver function, kidney function, blood lipid and potassium; and echocardiographic parameters. Results: Among the 774 participants, 76 had experienced VTs and 698 PVCs. The original site of IVAs was 2.38 times more likely to be in the RVOT than the LVOT, with the ratio for RVOT/LVOT = 2.38. IVAs usually occurred in participants between 50 and 70 years old and exhibited a decreasing incidence after 70 years of age. IVAs derived from the His bundle were more common in older participants, with a mean age of 60.4 ± 10.4 years, while IVAs derived from the fascicular were more common in younger patients, with a mean age of 36.08 ± 16.01 years. Compared with the LVOT group, the RVOT group was younger, 51.91 ± 14.65 years vs 46.95 ± 14.95 years, respectively (P < .001). PVCs in the RVOT group were more common in women, with the ratio of females/males = 2.10, and no gender difference existed in the overall incidence of IVAs in the LVOT group (P > .05). The most common cardiovascular comorbidities of outflow tract ventricular arrhythmias (OTVAs) were hypertension, coronary heart disease, and hyperlipidemia, while the most common noncardiovascular comorbidities were diabetes, ischemic stroke, and thyroid disease. The red-blood-cell counts, hemoglobin, creatinine, and gamma-glutamyl transpeptidase (GGT) of the LVOT group were higher than those from the RVOT, with P = .008, P = .009, P = .001, and P < .001, respectively. The left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVS), and left ventricular posterior wall thickness (LVPWT) in the LVOT group were larger than those in the RVOT group (P <.001), while the LVOT group's left ventricular ejection fraction (LVEF%) was lower than that of the RVOT group. Conclusions: The outflow tract served as the major original site of IVAs, and significant differences existed between participants in the LVOT and RVOT groups in age; gender; comorbidities; results of laboratory examinations, including red-blood-cell counts, hemoglobin, creatinine, and GGT; and echocardiographic parameters, including LVEF%, LAD, LVEDD, IVS, and LVPWT.

Trimetazidine Effect on the Cardiac Autonomic Nerve System after Percutaneous Coronary Intervention in Coronary Heart Disease: A Propensity-score Matched Study.

OBJECTIVE: To assess the effects of trimetazidine (TMZ) added to conventional drug therapy on cardiac autonomic nervous CANS in patients with coronary heart disease (CHD) after the percutaneous coronary intervention (PCI). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY:  Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei, China, from May 2018 to September 2019. METHODOLOGY: The study included 50 patients with CHD after a successful PCI who received trimetazidine plus conventional therapy were included as cases (exposed group), and 50 matched patients were identified as controls (non-exposed group). Heart rate (HR) and heart rate variability (HRV) parameters including sympathetic activity (SDNN, LF), parasympathetic activity (RMSSD, pNN50, SDSD, HF), and sympathovagal balance (LF/HF ratio) were used to evaluate CANS function. RESULTS: There were no statistical differences in the HR and HRV parameters before and after PCI (p>0.05). In the non-exposed group, conventional therapy significantly improved the HRV parameters (all p<0.05), while not affecting HR (p>0.05). In the exposed group, all HRV parameters except HR were improved after 4 weeks of treatment. After 4 weeks of treatment, the exposed group had higher parasympathetic-nerve activity, lower sympathetic-nerve activity, and LF/HF ratio compared to the non-exposed group (all p<0.05). CONCLUSIONS: The application of TMZ based on conventional therapy effectively improved the CANS in CHD patients who underwent PCI. KEY WORDS: Coronary heart disease, Percutaneous coronary intervention, Trimetazidine, Cardiac autonomic nervous system, Heart rate variability.

S-R index in V1/V3 serves as a novel criterion to discriminate idiopathic premature ventricular contractions originating from posteroseptal right ventricular outflow tract versus right coronary cusp.

AIM: The current study aimed to establish a novel electrocardiographic (ECG) criterion for discrimination of idiopathic premature ventricular contractions (PVCs) originating from posteroseptal right ventricular outflow tract (sRVOT-p) versus right coronary cusp (RCC). METHODS: A total of 76 patients with idiopathic PVCs who underwent mapping and successful ablation were retrospectively included. Among them, 37 patients had PVCs from sRVOT-p origin and 39 patients from RCC origin. The surface ECGs during PVCs were recorded. S-R different index in V1/V3 was calculated with the following formula of 0.134*V3R-0.133*V1S. RESULTS: ECG characteristics showed wider total QRS duration, smaller R-wave amplitude on lead V2-V5, and larger S-wave amplitude on lead V1-V3 in sRVOT-p origin than RCC origin. Lead V3 was the most common transitional lead in two groups. Receiver operating characteristic (ROC) curve analysis showed that S-wave amplitude on lead V1 exhibited the largest AUC of 0.772, followed by the AUC of R-wave amplitude on lead V3 of 0.771. Subsequently, 0.134*V3R-0.133*V1S index was obtained by multiplication, subtraction, sum, and division of these ECG measurements, which exhibited the largest AUC of 0.808. The optimal cut-off value was -0.26 for differentiating RCC from sRVOT-p origin, with the sensitivity of 78.4% and specificity of 77.8%. Moreover, 0.134*V3R-0.133*V1S index was superior to previous criteria in analysis of PVCs originating from sRVOT-p and RCC. CONCLUSIONS: 0.134*V3R-0.133*V1S is a novel ECG criterion to discriminate sRVOT-p from RCC origin in patients with idiopathic PVCs, which may provide guidance for approach of radiofrequency catheter ablation.

Two Novel Mutations (G774A and A1685G) Causing Coagulation Factor XII Deficiency in a Patient with Acute Inferior Myocardial Infarction.

OBJECTIVE: To identify the gene mutation of the coagulation factor XII (FXII) in a patient with FXII deficiency and acute inferior myocardial infarction. METHODS: The proband was a 51-year-old Chinese man who was diagnosed with acute inferior myocardial infarction and had a history of FXII deficiency. The patient presented with a prolonged activated partial thromboplastin time (160 s) and decreased FXII activity (2.3%) and FXII antigen (1%). DNA sequence analysis of the FXII gene was performed by next generation sequencing. The mutant FXII cDNAs were constructed in an expression plasmid vector and transfected into 293T cells. The expression of FXII antigen was detected by western blot. RESULTS: Sequencing of the FXII gene revealed two novel heterozygous mutations, one at exon 8 (G774A; p: W258X) and the other at exon 14 (A1685G; p: D562G). Western blot showed that the FXII antigens were detected only in the supernatant and whole cell lysate of the wild-type and A1685G mutant type, but not in G774A or G774A plus the A1685G mutant type. In addition, the results showed that secretion but not synthesis of A1685G mutant protein was markedly reduced compared to the wild type. CONCLUSION: The present study indicated that the G774A mutation might impair the secretion and synthesis of FXII protein, while the A1685G mutation only influences the secretion of FXII protein. The definition of these new mutations could be useful tools for analyzing the intracellular protein transport and structure-function relationship of FXII protein transport in the future.

Renal sympathetic denervation attenuates left ventricle hypertrophy in spontaneously hypertensive rats by suppressing the Raf/MEK/ERK signaling pathway.

OBJECTIVE: To explore the effect of renal sympathetic denervation (RSD) on left ventricle hypertrophy and the Raf/MEK/ERK signaling pathway in spontaneously hypertensive rats (SHRs). METHODS: SHRs were divided into SHR, SHR + Sham, SHR + RSD and SHR + U0126 groups, with WKY rats as the baseline controls. The blood pressure of rats was observed, while myocardial fibrosis was evaluated through Masson staining. Thereafter, real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to determine the levels of myocardial-hypertrophy-related markers, and Western blotting was used to measure the activity of the Raf/MEK/ERK signaling pathway. RESULTS: In comparison with the WKY group, significant increases were observed in the systolic pressure and diastolic pressure of rats from the other four groups at different time points after surgery. In addition, rats in these groups had obvious increases in LVMI, renal NE and IVSd and decreases in LVEDd, LVEF and LVFS. In addition, the CVF of myocardial tissues was increased, with the upregulation of ANP, BNP and ß-MHC and the downregulation of α-MHC. For the activity of the Raf/MEK/ERK signaling pathway, the levels of p-Raf/Raf, p-MEK/MEK and p-ERK1/2/ERK1/2 were all remarkably elevated (all P < .05). Further comparison with the SHR group showed that the above indexes in the rats were significantly improved in the RSD group and SHR + U0126 group (all P < .05). CONCLUSION: RSD may decrease blood pressure, mitigate hypertension-induced left ventricle hypertrophy and improve cardiac function efficiently in SHRs via the suppression of the Raf/MEK/ERK signaling pathway.

Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects.

Contrast-induced acute kidney injury (CI-AKI) is a severe complication caused by intravascular applied radial contrast media (CM). Pyroptosis is a lytic type of cell death inherently associated with inflammation response and the secretion of pro-inflammatory cytokines following caspase-1 activation. The aim of the present study was to investigate the protective effects of acetylbritannilactone (ABL) on iopromide (IOP)-induced acute renal failure and reveal the underlying mechanism. In vivo and in vitro, IOP treatment caused renal damage and elevated the caspase-1 (+) propidium iodide (PI) (+) cell count, interleukin (IL)-1ß and IL-18 levels, lactate dehydrogenase (LDH) release, and the relative expression of nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD), suggesting that IOP induces AKI via the activation of pyroptosis. Furthermore, the pretreatment of ABL partly mitigated the CI-AKI, development of pyroptosis, and subsequent kidney inflammation. These data revealed that ABL partially prevents renal dysfunction and reduces pyroptosis in CI-AKI, which may provide a therapeutic target for the treatment of CM-induced AKI.

Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) alleviates myocardial hypoxia-reoxygenation injury by inhibiting oxidative stress and ameliorating mitochondrial dysfunction.

Oxidative stress and mitochondrial dysfunction are considered to be activators of apoptosis and serve a pivotal role in the pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) is a multifunctional protein that processes the cellular response to DNA damage and oxidative stress. Little is known about the role of APE1 in the pathogenesis of MI/R injury. The aim of the present study was to investigate the effects of APE1 on hypoxia-reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and the underlying mechanism responsible. It was demonstrated that H/R decreased cell viability and increased lactic dehydrogenase (LDH) release, as well as reducing APE1 expression in H9c2 cells. However, APE1 overexpression induced by transfection with APE1-expressing lentivirus significantly increased H9c2 cell viability, decreased LDH release, decreased apoptosis and reduced caspase-3 activity in H/R-treated H9c2 cells. APE1 overexpression ameliorated the H/R-induced increases in reactive oxygen species and NAPDH oxidase expression, as well as the decreases in superoxide dismutase activity and glutathione expression. Furthermore, APE1 overexpression increased mitochondrial membrane potential and ATP production, stabilized electron transport chain activity (as illustrated by increased NADH-ubiquinone oxidoreductase, succinate dehydrogenase, coenzyme Q-cytochrome c oxidoreductase and cytochrome c oxidase activities) and decreased the ratio of B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 in H/R, improving mitochondrial dysfunction. In conclusion, the results of the present study suggest that APE1 alleviates H/R-induced injury in H9c2 cells by attenuating oxidative stress and ameliorating mitochondrial dysfunction. APE1 may therefore be used as an effective treatment for MI/R injury.

IGF-1 deletion affects renal sympathetic nerve activity, left ventricular dysfunction, and renal function in DOCA-salt hypertensive mice.

To determine the influence of IGF-1 deletion on renal sympathetic nerve activity (RSNA), left ventricular dysfunction, and renal function in deoxycorticosterone acetate (DOCA)-salt hypertensive mice. The DOCA-salt hypertensive mice models were constructed and the experiment was classified into WT (Wild-type mice) +sham, LID (Liver-specific IGF-1 deficient mice) + sham, WT + DOCA, and LID+ DOCA groups. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IGF-1 levels in mice. The plasma norepinephrine (NE), urine protein, urea nitrogen and creatinine, as well as RSNA were measured. Echocardiography was performed to assess left ventricular dysfunction, and HE staining to observe the pathological changes in renal tissue of mice. DOCA-salt induction time-dependently increased the systolic blood pressure (SBP) of mice, especially in DOCA-salt LID mice. Besides, the serum IGF-1 levels in WT mice were decreased after DOCA-salt induction. In addition, the plasma NE concentration and NE spillover, urinary protein, urea nitrogen, creatinine and RSNA were remarkably elevated with severe left ventricular dysfunction, but the creatinine clearance was reduced in DOCA-salt mice, and these similar changes were obvious in DOCA-salt mice with IGF-1 deletion. Moreover, the DOCA-salt mice had tubular ectasia, glomerular fibrosis, interstitial cell infiltration, and increased arterial wall thickness, and the DOCA-salt LID mice were more serious in those aspects. Deletion of IGF-1 may lead to enhanced RSNA in DOCA-salt hypertensive mice, thereby further aggravating left ventricular dysfunction and renal damage.

Coenzyme Q10 combined with trimetazidine in the prevention of contrast-induced nephropathy in patients with coronary heart disease complicated with renal dysfunction undergoing elective cardiac catheterization: a randomized control study and in vivo study.

BACKGROUND: Contrast-induced nephropathy (CIN) is one of the common hospital-acquired acute renal failures. The purpose of this study was to investigate whether Coenzyme Q10 (CoQ10) and trimetazidine (TMZ) can prevent the occurrence of CIN after elective cardiac catheterization in patients with coronary artery disease complicated with renal dysfunction. METHODS: Consecutive coronary artery disease patients with renal insufficiency scheduled for coronary angiography were enrolled in randomized, paralleled, double-blind, controlled trial. The development of CIN was occurrence at the 48 or 72 h after the procedure. The changes of serum creatinine (SCr), eGFR, and Cys-C within 72 h after the procedure were measured and compared. In vivo contrast medium (CM)-induced acute kidney injury (AKI) animal model was established, and CoQ10 plus TMZ was orally administrated to evaluate its renal protective effect. RESULTS: 150 patients with renal insufficiency were enrolled finally. CIN occurred in 21 (14.00%) of the 150 patients. 72 h after the procedure, the incidence of CIN was significantly lower in CoQ10 plus TMZ group compared with control group (6.67 vs. 21.3%, p = 0.01). No cardiac death occurred in this study. No side effects were observed after administration of CoQ10 and TMZ. In vivo test demonstrated that CoQ10 and TMZ could significantly reduce the concentration of blood urea nitrogen (BUN) and SCR induced by CM i.v. injection, as well as tubular pathological injuries. Meanwhile, CoQ10 and TMZ could significantly reduce the oxidation stress in kidneys from CM-AKI animals. CONCLUSION: CoQ10 plus TMZ could decrease the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization, and their effect may be due to its strong anti-oxidation effect.