A preliminary study of minimal left atrial appendage occlusion using Watchman under the guidance of fluoroscopy.

BACKGROUND: Left atrial appendage occlusion (LAAO) has been considered an alternative treatment to prevent embolic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it carries a risk of general anesthesia or esophageal injury if guided by transesophageal echocardiography (TEE). AIMS: We aimed to investigate the feasibility and safety of minimal LAAO (MLAAO) using Watchman under fluoroscopy guidance alone in patients with NVAF. METHODS: A total of 249 consecutive patients with NVAF who underwent LAAO using the WATCHMAN device were divided into two groups: the Standard LAAO (SLAAO) group and the MLAAO group. Procedural characteristics and follow-up results were compared between the two groups. RESULTS: There was no statistically significant difference in the rate of successful device implantation (p > 0.05). Fluoroscopy time, radiation exposure dose, and contrast medium usage in the MLAAO group were higher than those in the SLAAO group (p < 0.001). The procedure time and hospitalization duration were significantly lower in the MLAAO group than those in the SLAAO group (p < 0.001). The occluder compression ratio, measured with fluoroscopy, was lower than that measured with TEE (17.63 ± 3.75% vs. 21.69 ± 4.26%, p < 0.001). Significant differences were observed between the SLAAO group and the MLAAO group (p < 0.05) in terms of oropharyngeal/esophageal injury, hypotension, and dysphagia. At 3 months after LAAO, the MLAAO group had a higher incidence of residual flow within 1-5 mm compared to the SLAAO group, although the difference was not statistically significant. CONCLUSION: MLAAO guided by fluoroscopy, instead of TEE, without general anesthesia simplifies the operational process and may be considered safe, effective, and feasible, especially for individuals who are unable to tolerate or unwilling to undergo TEE or general anesthesia.

Comparison of cardiac function and structure after left atrial appendage occlusion without versus with ablation in patients with non-valvular atrial fibrillation: a retrospective study.

The Aim of this study was to investigate the long-term impact of left atrial appendage occlusion (LAAO) on cardiac function and structure in patients with non-valvular atrial fibrillation (NVAF). 157 patients with NVAF who underwent LAAO or combined with ablation were included and divided into simple LAAO group or combined group. Long term impact of LAAO on cardiac function and structure were evaluated. Results showed that the procedures were performed successfully with 6.4% complications. During follow-up, there was a significant decrease of left atrial anteroposterior diameter (LAAD) at 6 months and a significant increase of left ventricular end-diastolic dimension (LVEDD) at 12 months after LAAO. A significant decrease in plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was noted at 3 months, 6 months and 12 months after procedure. There was a significant decrease of LAAD, LVEDD, left ventricular end-systolic dimension (LVESD) and NT-proBNP levels in combined group at 3 months, 6 months and 12 months post- procedure, while an increase of left ventricular ejection fraction (LVEF). Meanwhile, no significant change of LAAD, LVEDD, LVESD, NT-proBNP and LVEF was seen in simple LAAO group at 3 months follow-up, but a decrease of NT-proBNP during 6 months and 12 months follow-up. Compared with simple LAAO group, combined group was associated with a significant increase of residual flow. In conclusion, LAAO has no significant effect on cardiac structure and function but can significantly reduce NT-proBNP. The improvement of cardiac structure and function in combined therapy comes from the result of ablation, not LAAO.

Fasting blood glucose predicts high risk of in-stent restenosis in patients undergoing primary percutaneous coronary intervention: a cohort study.

Objectives. Studies have shown that fasting blood glucose (FBG) is closely associated with poor prognosis in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI), but its association with in-stent restenosis (ISR) is still unclear. Therefore, this study was to explore the association between FBG with ISR in patients with CHD after PCI. Design. In this cohort study, we included 531 patients with CHD who underwent PCI. Logistic regression, receiver operating characteristic (ROC), subgroup analysis and restricted cubic spline (RCS) were used to assess the association between FBG with ISR. Results. A total of 124 (23.4%) patients had ISR. Patients with higher levels of FBG had higher incidence of ISR compared to those with lower levels of FBG (p = 0.002). In multivariable logistic regression analyses, higher levels of FBG remained strongly associated with higher risk of ISR (as a categorical variable, OR: 1.89, 95% CI: 1.21-2.94, p = 0.005; as a continuous variable, OR: 1.12, 95% CI: 1.03-1.23, p = 0.011). ROC analysis also showed that FBG might be associated with the occurrence of ISR (AUC = 0.577, 95% CI: 0.52-0.64, p = 0.013). Subgroup analyses showed the association of FBG with ISR was also stable in several subgroups (< 60 years or ≥ 60 years, male, with or without smoking, without diabetes and without hypertension). And RCS analysis showed that FBG was linearly and positively associated with the risk of ISR. Conclusions. Higher levels of FBG were closely associated with higher risk of ISR in patients with CHD after PCI.

Construction of atrial fibrillation-related circRNA/lncRNA-miRNA-mRNA regulatory network and analysis of potential biomarkers.

BACKGROUND: The specific pathogenesis of atrial fibrillation (AF) remains unclear. In this study, we examined the expression of differential messenger RNAs (mRNAs), circular RNAs (circRNAs), and long-stranded noncoding RNAs (lncRNAs) from human peripheral blood mononuclear cells to initially construct a circRNA/lncRNA-miRNA-mRNA ceRNA regulatory network to explore the pathogenesis of AF and to screen for potential biomarkers. METHODS: A total of four pairs of AF cases and healthy subjects were selected to detect differentially expressed mRNAs, circRNAs, and lncRNAs in peripheral blood mononuclear cells by microarray analysis. And 20 pairs of peripheral blood from AF patients and healthy subjects were selected for validation of mRNA, circRNA, and lncRNA by quantitative real-time PCR (qRT-PCR).The relevant ceRNA networks were constructed by GO and KEGG and correlation analysis. RESULTS: The results showed that compared with healthy subjects, there were 813 differentially expressed mRNAs (DEmRNAs) in peripheral blood monocytes of AF, including 445 upregulated genes and 368 downregulated genes, 120 differentially expressed circRNAs (DEcircRNAs), including 65 upregulated and 55 downregulated, 912 differentially expressed lncRNAs (DElncRNAs), including 531 upregulated and 381 downregulated lncRNAs. GO and KEGG analysis of DERNA revealed the biological processes and pathways involved in AF. Based on microarray data and predicted miRNAs, a ceRNA network containing 34 mRNAs, 212 circRNAs, 108 lncRNAs, and 38 miRNAs was constructed. CONCLUSION: We revealed a novel ceRNA network in AF and showed that downregulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR-486-5p expression and had a potential targeting relationship with miR-486-5p.

Using the Perimeter-Derived Diameter and Ellipticity Index of the Left Atrial Appendage Landing Zone to Predict Watchman Occluder Size.

Objective: The Watchman 2.5 occluder device is a useful device to treat atrial fibrillation (AF), and predicting the size of the Watchman 2.5 occluder device is important to the therapeutic efficacy. To use cardiac computed tomography angiography (CCTA) to predict the size of a Watchman 2.5 occluder device is a potential approach. Methods: The CCTA was used to individually plan the left atrial appendage (LAA) landing zone and measure the longest and shortest diameters, in addition to the perimeter. The average diameter, the perimeter-derived diameter (PDD), and the ellipticity index (EI) are then calculated from the above values. The longest diameter, the shortest diameter, the average diameter, and PDD of the landing zone were used to predict the occluder size. The size of the occluder was predicted using the longest diameter, the shortest diameter, the average diameter, and the PDD, which is then compared to the actual size. Results: There were differences between the predicted and actual values of the four groups, with the smallest variability in PDD (P = .007). There was a strong positive correlation between the four groups and the actual occluder size, with the strongest PDD correlation (r = 0.941, P < .001). The prediction accuracy ranged from 44.1% to 90.1% for different methods, with PDD having the highest prediction accuracy. The ROC curve of EI was predicted and plotted using the longest diameter method recommended in the Watchman's instructions, and the area under the curve was 0.905 (95%Confidence Interval (CI) 0.847-0.963), with a cut-off value of 1.198, a sensitivity of 88.9% and a specificity of 82.7%. LAAs with an EI<1.198 had similar accuracy in predicting occluder size, regardless of whether the longest diameter (93.94%) or PDD (87.88%) (P = .344) method was used. However, the kappa test showed poor agreement between the two methods (Kappa = 0.093). When EI ≥ 1.198 (n = 45), the accuracy of PDD in predicting occluder size was 93.33%, which is significantly higher than predictions of the longest diameter (28.9%) (P < .001). Conclusions: The longest diameter and the PDD methods predicted occluder size with a high degree of accuracy when the LAAs EI < 1.198; the PDD method is suggested to be a preferred method to treatAF.

A Randomized Trial of Preoperative Planning of Left Atrial Appendage Occlusion Using Cardiac Computed Tomography Angiography.

Objective. To evaluate the value of individualized planning of left atrial appendage occlusion (LAAO) using cardiac computed tomography angiography (CCTA) reconstruction techniques. Methods. A total of 96 patients treated for LAAO with the Watchman occluder were included in this study. All patients were randomized by random number table in a 2:1 ratio into the CCTA (+) and CCTA (-) groups according to whether CCTA was performed preoperatively. 3D cardiac reconstruction was performed preoperatively in the CCTA (+) group to plan the location of the atrial septal puncture site, left atrial appendage(LAA) landing zone, predict the size of the occluder and simulate occluder release. In the CCTA(-) group, only transesophageal echocardiography (TEE) and fluoroscopy were used to guide LAAO. Results. The number of occluders used in a single procedure (1.06 ± .24 vs 1.22 ± .42), the number of intraoperative angiography positions (1.23 ± .58 vs 2.28 ± .85) and the procedure time (45.88 ± 5.08 vs 62.44 ± 5.60) in the CCTA(+) group were lower than in the CCTA(-) group (P < .05), and the first-attempt blocking success rate was higher than that of the CCTA(-) group (85.9% vs 65.6%, P = .021). Furthermore, the Bland-Altman plots showed good agreement between the longest diameter of the CCTA-predicted landing zone and the longest diameter of the actual landing zone (95% LoA -7.49, 10.24). A strong positive correlation was observed between the predicted compression ratio and the actual compression ratio (r = .890, P < .001). In addition, a strong positive correlation was found between the CCTA-predicted longest diameter of the landing zone and the actual occluder size (r = .863, P < .001). Conclusion. Accurate planning for LAAO using preoperative CCTA can reduce intraoperative angiography positions and occluder changes, shorten the procedure time, increase the success rate of first-attempt blocking and reduce the difficulty of the procedure.

Effects of Left Atrial Appendage Closure on Neuroendocrine Function in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND The left atrial appendage (LAA) is an organ with neuroendocrine function. It remains unclear whether left atrial appendage closure (LAAC) has physiological effects on neuroendocrine function in patients with nonvalvular atrial fibrillation (NVAF). In the present study, we aimed to investigate the effects of LAAC on neuroendocrine function in patients with NVAF. MATERIAL AND METHODS We enrolled 20 patients with NVAF treated by LAAC in Jiangsu Taizhou People's Hospital from October 2019 to October 2020. Blood samples were collected 1 day before LAAC and 12 months after LAAC. Plasma concentrations of adrenaline, aldosterone, pro-atrial natriuretic peptide (NT-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured. RESULTS LAAC was successfully performed in all patients, without serious complications. Compared with the preoperative levels, there was no significant difference in the levels of NT-proANP, NT-proBNP, and epinephrine at 12 months after LAAC (P>0.05). However, there was a significant decrease in aldosterone level at 12 months post-procedure (209.04±132.98 pg/ml) compared with pre-procedure baseline (279.08±166.88 pg/ml, P=0.04). There was no correlation between the compression rate of the occlusion and the reduction of aldosterone (Kendall's Tau-b=0.159, P=0.351). CONCLUSIONS LAAC can be safely and effectively performed in NVAF patients, and showed no significant effect on the adrenergic system and natriuretic peptides, but had an influence on the RAAS.

Influencing Factors of Recurrence of Nonvalvular Atrial Fibrillation after Radiofrequency Catheter Ablation and Construction of Clinical Nomogram Prediction Model.

Purpose: This study sought to investigate the predictive factors for atrial fibrillation (AF) recurrence in patients after radiofrequency ablation (RFCA) and construct a nomogram prediction model for providing precious information of ablative strategies. Methods: A total of 221 patients with AF who underwent RFCA were enrolled. Univariate and multivariate Cox regression were used to screen the predictors of recurrence. The receiver operating characteristic (ROC) curve and the Kaplan-Meier (K-M) curve were drawn to analyze the value of predictors. The nomogram model was further constructed to predict the recurrence of AF in patients after RFCA. Results: There were 59 cases of AF recurrence after RFCA. Monocyte count/high-density lipoprotein cholesterol (MHR), AF course (COURSE), coronary heart disease (CHD), and AF type (TYPE) were the independent risk factors for predicting AF recurrence after RFCA. Accordingly, a nomogram prediction model based on MHR, COURSE, CHD, and TYPE was constructed with a C-index of 0.818 (95% CI: 0.681∼0.954), while the C-index of verification was 0.802 (95% CI: 0.658∼0.946). Conclusions: Preoperative MHR, COURSE, CHD, and TYPE were independent risk factors for predicting recurrence of AF after RFCA. The nomogram model based on MHR, COURSE, CHD, and TYPE can be used to predict the recurrence of AF after RFCA accurately and individually.

Circular RNA expression profiles during the differentiation of human umbilical cord-derived mesenchymal stem cells into cardiomyocyte-like cells.

So far, there were no reports on circular RNA (circRNA) expression profiles in the differentiation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) into cardiomyocyte-like cells induced by 5-aza. In this study, hUCMSCs were isolated from umbilical cords and induced with 5-aza for 14 days. Immunofluorescence staining, real-time reverse transcription polymerase chain reaction (RT-PCR), and western blot of cardiac troponin I and α-sarcomeric actin on hUCMSCs between Days 14 and 0 were performed. The expression profile of circRNAs was analyzed by microarray and validated with RT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the functions of differentially expressed genes and related pathways. The connections between circRNAs and microRNAs were explored by using Cytoscape. The results showed that a total of 226 circRNAs were calculated as differentially expressed during the differentiation. Among them, 127 were upregulated and 99 were downregulated. We selected circRNAs that were upregulated by more than five-fold and downregulated by more than three-fold. Ultimately, 74 differentially expressed circRNAs that were highly conserved on Day 14 after induction compared to Day 0 were identified. Among them, 41 were upregulated and 33 were downregulated. Four upregulated circRNAs (circRNA_01536, circRNA_04411, circRNA_09169, and circRNA_09905) and four downregulated circRNAs (circRNA_00699, circRNA_01183, circRNA_01978, and circRNA_16804) were randomly confirmed by RT-PCR. GO analysis suggested a number of cell proliferation and differentiation related physiological processes and pathways, such as the Wnt signaling pathway and others. Network analysis uncovered three potential key circRNAs, that is, circRNA_05432, circRNA_08441, and circRNA_01536.

MicroRNA-122 promotes cardiomyocyte hypertrophy via targeting FoxO3.

OBJECTIVE: -microRNAs (miRNAs) have emerged as novel regulators for cardiac hypertrophy. MiR-122 is well recognized as a promising therapeutic target in liver disease, whereas recently plays important roles in cardiovascular diseases. The current study aimed to explore the effect of miR-122 on the pathogenesis of cardiomyocyte hypertrophy. METHODS AND RESULTS: -The cardiomyocytes isolated from the neonatal rat ventricular cardiomyocytes (NRVMs) were collected and performed to Angiotensin II (Ang II) administration. We observed a dramatically increased miR-122 expression in hypertrophic cardiomyocytes. The NRVMs transfected with miR-122 mimic or negative control were utilized for the functional analysis. Overexpression of miR-122 increased the morphology size of cardiomyocytes and promoted the pro-hypertrophic genes expression, whereas downregulated the anti-hypertrophic genes upon Ang II stimulation. The bioinformatics analysis and luciferase reporter assays exhibited that miR-122 directly targeted FoxO3 and attenuated its gene level in hypertrophic cardiomyocytes. Moreover, miR-122 negatively regulated FoxO3 but promoted calcineurin signaling pathway activation. Importantly, FoxO3 overexpression significantly reversed the effect of miR-122 on cardiomyocyte hypertrophy. CONCLUSION: -Collected, our finding demonstrated that miR-122 accelerated the development of cardiomyocytes hypertrophy partially via directly regulation of FoxO3-calcineurin pathway.

Early and long-term effect of thoracic endovascular aortic repair for Stanford B aortic dissection.

BACKGROUND: Uncomplicated Stanford B acute aortic dissection (AAD) is generally treated with medical management; whereas complicated dissections require surgery or thoracic endovascular aortic repair (TEVAR). Studies have demonstrated that long-term outcomes with medical management are suboptimal. Therefore, we sought to investigate the early and long-term clinical efficacy of TEVAR for Stanford B AAD. MATERIALS AND METHODS: From March 2004 to January 2008, 63 consecutive patients were treated and retrospectively placed into either one of the two groups, the TEVAR group (n = 42) and the medicine group (n = 21). All TEVAR procedures were performed in the acute phase. The changes of true and false lumen diameter were monitored with computed tomography angiography examinations in the thoracic aorta at the level of the stented segment at long-term follow-up. RESULTS: As compared with the medicine group, the age at intervention in the TEVAR group was higher (p < 0.05), and they also had more patent false lumen in this group. Patients in the TEVAR group had significantly longer hospital stays than those in the medicine group (p < 0.01). The incidence of the early events was not significantly different between the two groups. The incidence of aortic-related late events and late death were significantly higher in the medicine group than those in the TEVAR group. Log-rank tests demonstrated that patients treated with medical management had significantly more late adverse events than did those treated with TEVAR (p < 0.01). At 1-year follow-up, the true lumen diameter in the thoracic aorta at the level of the stented segment increased significantly after TEVAR, and the mean reduction of false lumen diameter was highly significant. The remodeling was stable at 3 and 5 years after TEVAR. CONCLUSION: Patients with Stanford B AAD treated with TEVAR experienced fewer late adverse events than those treated with medical management, TEVAR could be an effective treatment for Stanford B AAD.

Potential of 5-azacytidine induction decidual stromal cells from maternal human term placenta towards cardiomyocyte-like cells in serum-free medium.

Decidual stromal cells (DSCs) from maternal term placenta represent a potential source of cells for the treatment of cardiovascular and graft-versus-host diseases. However, it is not clear whether DSCs could be induced towards cardiomyocyte-like differentiation. We chose the placentas which should bred male new-baby. We isolated DSCs from placenta by tissue adherence. The morphology, immunophenotype, and multi-lineage potential were analyzed. Karyotype analysis (G-band) was performed to determine the source and karyotype stability of DSCs. DSCs were induced by 5-azacytidine. Expression of Myf5, α-cardiac actin, Cardiac troponin T (cTnT) and GAPDH was assessed by PCR, and cTnT expression was also analyzed by immunofluorescence. Karyotype analyses indicated that cells were derived from the maternal matrix. After induction with 5-azacytidine, DSCs expressed the cardiac-specific markers Myf5, myogenin and cTnT, indicating differentiation towards cardiomyocyte-like cells.

Risk factors of early and late mortality after thoracic endovascular aortic repair for complicated stanford B acute aortic dissection.

BACKGROUND AND AIM OF THE STUDY: The risk factors associated with death in complicated Stanford B acute aortic dissection (AAD) after thoracic endovascular aortic repair (TEVAR) are poorly understood. The aim of this study was to evaluate the early and late events and mortality of complicated Stanford B AAD associated with TEVAR. METHODS: Sixty-two patients with complicated Stanford B AAD undergoing TEVAR were included in this study. RESULTS: Primary technical success of TEVAR was achieved in 61 (98.39%) cases. The early mortality rate was 9.68%. Procedural type I endoleak (p = 0.007, OR = 7.71, 95% CI: 1.75-34.01) and cardiac tamponade (p = 0.010, OR = 8.86, 95% CI: 1.70-4 6.14) were the significant predictors of early death in the multivariate model. The late mortality was 16.07%. Cox regression analysis revealed rupture of false lumen (p = 0.001, hazard ratio = 21.96, 95% CI: 3.02-82.12), postoperative myocardial infarction (p = 0.001, hazard ratio = 9.86, 95% CI: 2.12-39.64), and acute renal failure (p = 0.024, hazard ratio = 3.98, 95% CI: 1.26-12.11) to be independent risk factors of late mortality. CONCLUSIONS: Type I procedural endoleak and cardiac tamponade were the significant predictors of early death in patients of complicated Stanford B AAD undergoing TEVAR. Rupture of false lumen, postoperative myocardial infarction, and acute renal failure were the independent risk factors for late death after TEVAR.

Monitoring the biology stability of human umbilical cord-derived mesenchymal stem cells during long-term culture in serum-free medium.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have an immunosuppressive effect. The biological stability of MSCs in serum-free medium during long-term culture in vitro has not been elucidated clearly. The morphology, immunophenotype and multi-lineage potential were analyzed at passages 3, 5, 10, 15, 20, and 25 (P3, P5, P10, P15, P20, and P25, respectively). The cell cycle distribution, apoptosis, and karyotype of human umbilical cord-derived (hUC)-MSCs were analyzed at P3, P5, P10, P15, P20, and P25. From P3 to P25, the three defining biological properties of hUC-MSCs [adherence to plastic, specific surface antigen expression, multipotent differentiation potential] met the standards proposed by the International Society for Cellular Therapy for definition of MSCs. The cell cycle distribution analysis at the P25 showed that the percentage of cells at G0/G1 was increased, compared with the cells at P3 (P < 0.05). Cells at P25 displayed an increase in the apoptosis rate (to 183 %), compared to those at P3 (P < 0.01). Within subculture generations 3-20 (P3-P20), the differences between the cell apoptotic rates were not statistically significant (P > 0.05). There were no detectable chromosome eliminations, displacements, or chromosomal imbalances, as assessed by the karyotyping guidelines of the International System for Human Cytogenetic Nomenclature (ISCN, 2009). Long-term culture affects the biological stability of MSCs in serum-free MesenCult-XF medium. MSCs can be expanded up to the 25th passage without chromosomal changes by G-band. The best biological activity period and stability appeared between the third to 20th generations.

Cystatin C, N-terminal probrain natriuretic peptides and outcomes in acute heart failure with acute kidney injury in a 12-month follow-up: Insights into the cardiorenal syndrome.

BACKGROUND: Cystatin C (Cys C) has been implicated as a prognostic marker in cardiovascular disease. The aim of this study was to evaluate the value of Cys C as a marker of acute kidney injury (AKI) in acute heart failure (AHF), the impact of Cys C and N-terminal probrain natriuretic peptides (NT-proBNP) on in-hospital and 12 months mortality were also investigated. MATERIALS AND METHODS: A total of 162 patients with AHF were enrolled. NT-proBNP, Cys C, serum creatinine (Scr), blood urea nitrogen (BUN) and parameters of echocardiography were measured for analyze. The in-hospital and 12 months mortality was analyzed. RESULTS: There was 28 (17%) of all AHF patients with AKI. Compared with no-AKI patients, the levels of Cys C (1.51 ± 0.34 vs. 1.32 ± 0.29, P = 0.003) and NT-proBNP (8163.87 ± 898.06 vs. 5922.45 ± 576.73, P = 0.001) were higher in AKI patients. Higher levels of NT-proBNP (odds ratio (OR) = 1.92, 95% confidence interval (CI): 2.19-10.98, P = 0.018, OR = 4.31, 95% CI: 2.35-9.82, P = 0.002, respectively) and Cys C (OR = 1.48, 95% CI: 1.75-4.16, P = 0.027, OR = 2.72, 95% CI: 1.92-4.28, P = 0.017, respectively) were independent association with the in-hospital and 12 months mortality. Cys C was positively correlated with NT-proBNP (r = 0.87, P < 0.001). Combining tertiles of Cys C and NT-proBNP improved risk stratification further. Compared with patients without AKIcysC, patients with AKIcysC was associated with higher in-hospital (7/28 vs. 10/134, P = 0.002) and 12-month mortality (13/28 vs. 32/134, P = 0.001). CONCLUSION: Cys C was not only a promising risk marker in patients hospitalized for AHF, but also an independent predictor of 12-month mortality. Combining tertiles of Cys C and NT-proBNP could be used to distinguish the mortality risk identification of patients with AHF. AKI was an independent predictor of in-hospital and 12-month mortality.

Hyperoside alleviates doxorubicin-induced myocardial cells apoptosis by inhibiting the apoptosis signal-regulating kinase 1/p38 pathway.

Background: Cardiotoxicity is a side effect of the anthracycline broad-spectrum anti-tumor agent, doxorubicin (DOX). Hyperoside, a flavonoid glycoside extracted from many herbs, has anti-apoptotic and anticancer properties. However, its impact on the alleviation of DOX-induced apoptosis in cardiomyocytes remains elusive. Methods: The HL-1 cell line was treated with 100 µ M hyperoside for 1 h prior to treatment with 100 µ M hyperoside and 1 µ M DOX for 24 h. The cell counting kit-8 (CCK-8) assay was used to detect cell viability; DCFH-DA fluorescent probe was used to detect (reactive oxygen species) ROS; biochemical methods were used to detect the activity of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA); the degree of apoptosis following DOX insult was assessed using immunofluorescence staining and terminal deoxynucleotidyl transferase mediated deoxy uridine triphosphate nick end labeling (TUNEL) assay; the change in protein expression of apoptosis signal-regulating kinase 1 (ASK1), p38, and apoptosis markers was determined using western blot. Results: Hyperoside ameliorated DOX-induced oxidative stress in HL-1 cells, up-regulated GSH, SOD and CAT activity, reduced ROS production and inhibited MDA overproduction. Moreover, in addition to promoting HL-1 cell apoptosis, DOX administration also increased B-cell lymphoma (Bcl)-2-associated X-protein and cleaved caspase-3 protein levels and decreased Bcl-2 protein level. Hyperoside therapy, however, significantly reversed the impact of DOX on the cardiomyocytes. Mechanically, DOX treatment increased the phosphorylation of the ASK1/p38 axis whereas hyperoside treatment attenuated those changes. In a further step, hyperoside synergizes with DOX to kill MDA-MB-231 cells. Conclusions: Hyperoside protects HL-1 cells from DOX-induced cardiotoxicity by inhibiting the ASK1/p38 signaling pathway. Meanwhile, hyperoside maintained the cytotoxicity of DOX in MDA-MB-231 cells.

Case report: Widely split P' waves in a patient with focal atrial tachycardia.

Background: Widely split P waves in sinus rhythm have been reported previously. However, widely split P' waves in focal atrial tachycardia (AT) on a surface electrocardiogram (ECG) have rarely been reported. The electrophysiological mechanism is relatively difficult to clarify, requiring a electrophysiological study. Case summary: A 67-year-old patient, who had undergone two radiofrequency ablations for atrial fibrillation, presented with recurrent palpitation. During the palpitation episode, the 12-lead ECG showed AT with a 3:1 atrioventricular conduction rate. P' waves were markedly prolonged in duration and widely split in morphology. An electrophysiological study showed that the tachycardia arose from the left atrial appendage (LAA) and was conducted through two distinct pathways. The impulse of one pathway was transmitted solely via the superior part of the atrium, including the Bachmann bundle. The second pathway was conducted via the coronary sinus and transmitted the impulse from the LAA to the ventricle. After the site showed that the earliest activation was ablated, repeated intravenous infusion of isoprenaline and programmed atrial stimulation did not induce tachycardia. Conclusion: Widely split P' waves in AT indicate intra- and interatrial conduction blocks, which can be easily overlooked due to the presence of low-voltage areas. Therefore, an electrophysiological study is crucial for identifying the origin of the tachycardia and elucidating the mechanistic details.

DNA methylation cooperates with H3K9me2 at HCN4 promoter to regulate the differentiation of bone marrow mesenchymal stem cells into pacemaker-like cells.

Sick sinus syndrome (SSS) is a a life-threatening disease, and biological pacemakers derived from bone marrow mesenchymal stem cells (BMSCs) have practical clinical applications. Previous studies demonstrated that epigenetics plays an important role in the differentiation of BMSCs into pacemaker-like cells. However, the underlying mechanisms remain unclear. In the present study, we investigated the role of DNA methylation and histone methylation in pacemaker cells formation and found that changes in DNA and H3K9 methylation occur in the promoter region of the pacemaker cell-specific gene HCN4. In addition, the combined addition of methylation inhibitors was able to improve the efficiency of transduction of Tbx18 in inducing the differentiation of BMSCs into pacemaker-like cells. In vitro experiments have shown that inhibition of DNA methylation and H3K9 methylation can enhance the activity of the HCN4 promoter activity, and both can affect the binding of the transcription factor NKx2.5to the HCN4 promoter region. Further research on the interaction mechanism between DNA methylation and H3K9me2 in the HCN4 promoter region revealed that the two may be coupled, and that the methylesterase G9a and DNMT1 may directly interact to bind as a complex that affects DNA methylation and H3K9me2 regulation of HCN4 transcription. In conclusion, our studies suggest that the mutual coupling of DNA and H3K9 methylation plays a critical role in regulating the differentiation of BMSCs into pacemaker-like cells from the perspective of interactions between epigenetic modifications, and combined methylation is a promising strategy to optimise pacemaker-like cells for in vitro applications.

Exposure to perchlorate, nitrate, and thiocyanate and the prevalence of abdominal aortic calcification.

Perchlorate, nitrate, and thiocyanate are reported to affect human health. However, it is unclear about the associations between exposure to these chemicals and abdominal aortic calcification (AAC). A total of 959 individuals were included in a large representative survey. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography coupled with electrospray tandem mass spectrometry. AAC was diagnosed based on dual-energy X-ray absorptiometry (DXA). There were 276 (28.8%) cases of AAC among the participants. The level of urinary nitrate was significantly lower in AAC patients compared with non-AAC patients (36.4 mg/L [20.6, 59.5] vs. 42.4 [23.8, 68.3]; P = 0.013). In multivariable-adjusted logistic regression models, urinary nitrate was associated with the prevalence of AAC. Compared with the lowest quartile, the odds ratios (95% confidence intervals) across increasing quartiles were 1.06 (0.69-1.61; P = 0.799), 0.64 (0.41-1.00; P = 0.049) and 0.74 (0.47-1.15; P = 0.180). Restricted cubic splines suggested that urinary nitrate ranging between 43.7 and 115.4 mg/L was associated with a lower risk of AAC. Moderate exposure to nitrate was associated with a lower risk of AAC.

The effect of two different methods of planning landing zone for left atrial appendage closure by cardiac computed tomography angiography: a comparative study.

Background: To explore the value of 2 different methods for planning landing zone for left atrial appendage closure (LAAC) by cardiac computed tomography angiography (CCTA). Methods: A retrospective analysis was performed on the clinical data of patients who successfully underwent LAAC with the Watchman device at The Affiliated Taizhou People's Hospital of Nanjing Medical University from August 2020 to February 2022. Two different methods were used to plan the landing zone and measure the longest diameter, average diameter, depth, and perimeter of the landing zone. The difference between the 2 methods and the correlation between their measurements and occluder size were analyzed. Results: A total of 66 patients undergoing LAAC were included, with an average age of 69.35±7.1 years, of whom 30 (45.5%) were women. The mean error between the longest diameter measured by the traditional method and the actual value was 2.90±2.83 mm, and the mean absolute error (MAE) was 2.71 (1.17, 4.38) mm. The mean error between the longest diameter measured by the new method and the actual value was 0.9 (-0.13, 2.50) mm, and its MAE was 1.4 (0.40, 2.53) mm. The error of the longest diameter measured by the traditional method was larger than that measured by the new method (P<0.001). The mean error between the depth measured by the traditional method and the actual value was 1.40±3.45 mm, and the MAE was 2.36 (0.74, 4.58) mm. The mean error between the depth measured by the new method and the actual value was 0.10 (-1.33, 1.95) mm, and the MAE was 1.55 (0.60, 3.10) mm. Likewise, the depth error measured by the traditional method was larger than that measured by the new method (P<0.05). The correlation between the perimeter and the size of the occluder was the strongest (r=0.919, P<0.001). Conclusions: With CCTA, the new method is more accurate in planning landing zone than the traditional method. It is particularly important to select the occluder size for the patients with flat oval landing zone ostium.