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.

Dapagliflozin Attenuates Contrast-induced Acute Kidney Injury by Regulating the HIF-1α/HE4/NF-κB Pathway.

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) causes clinically acquired nephropathy in patients who undergo coronary interventions. Hypoxic injury to proximal tubular epithelial cells is a pathological mechanism of CI-AKI. Previous studies have shown that hypoxia activates HIF-1α/HE4/NF-κB to enhance renal fibrosis, and the SGLT-2 inhibitor luseogliflozin inhibits hypoxia-inducible factor (HIF)-1α expression to reduce the progression of diabetic nephropathy. However, the therapeutic effects and mechanisms of SGLT-2 inhibitors on CI-AKI are unclear. We explored the role of the HIF-1α/HE4/NF-κB pathway in CI-AKI and how dapagliflozin effectively treats CI-AKI by inhibiting this pathway. In vitro, cells were divided into the control, hypoxia, hypoxia + dapagliflozin, and hypoxia + pSilencer-HIF-1α groups. Cellular hypoxia, apoptosis, and related protein expression were evaluated by immunofluorescence, western blotting, and flow cytometry, respectively. Dapagliflozin significantly decreased oxygen consumption, HIF-1α, human epididymis protein 4 (HE4), NF-κB expression, and apoptotic cells compared with the control (P < 0.01). In vivo, rats were divided into the control (C), diabetes (D), diabetes + contrast media, and diabetes + contrast media + dapagliflozin groups. Rats in the latter 2 groups were treated with dapagliflozin for 2 days. CI-AKI was induced by intravenously injecting indomethacin, N-nitro-l-arginine methyl ester, and iohexol. The effects of dapagliflozin on CI-AKI rats were elucidated by assessing renal function, H&E staining, and immunohistochemistry. Serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores were increased in diabetes + contrast media rats compared with C, D, and diabetes + dapagliflozin + contrast media rats (P < 0.01). Thus, dapagliflozin may ameliorate CI-AKI through suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo.

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.

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.

A Comparative Study of Three Imaging Modalities for Size Selection of a Watchman Left Atrial Appendage Closure Device.

PURPOSE: To compare the results of computed tomography angiography (CTA), transesophageal echocardiography (TEE), and digital subtraction angiography (DSA) measurements and analyze their accuracy, correlation, and consistency in patients who have successfully undergone left atrial appendage closure (LAAC). MATERIALS AND METHODS: A total of 157 non-valvular atrial fibrillation (AF) patients who underwent LAAC with Watchman devices were included in the study. The maximum diameter and depth of LAA were recorded using CTA, TEE, and DSA. Correlations and agreements were compared. RESULTS: The LAAC procedure was performed successfully in all patients using the Watchman device. There was no significant difference between DSA and TEE measurements of the diameter of the LAA ostium. LAA ostium diameter obtained by CTA, however, was greater than that from DSA and TEE. Correlations were good between LAA ostium diameter measured by TEE, CTA, and DSA and Watchman device size. DSA measurements and actual device size showed the widest limits of agreement, followed by TEE; CTA measurements showed the narrowest limits of agreement. For LAA depth measurements, mean CTA measurements were higher than those of TEE and DSA. There was no significant difference in depth measurements among the three imaging modalities. CONCLUSION: CTA, TEE, and DSA measurements exhibited good correlations with Watchman device size. The ostium diameter and depth of the LAA measured by CTA were greater than those measured by TEE and DSA. The relevance and concordance of CTA measurements were the strongest.

Cryoballoon pulmonary vein isolation and left atrial appendage occlusion prior to atrial septal defect closure: A case report.

BACKGROUND: In patients who suffer from both atrial fibrillation (AF) and atrial septal defect (ASD), cryoballoon pulmonary vein isolation (PVI), sequential left atrial appendage (LAA) occlusion and ASD closure could be a strategy for effective prevention of stroke and right heart failure. CASE SUMMARY: A 65-year-old man was admitted to our institution due to recurrent episodes of palpitations and shortness of breath for 2 years, which had been worsening over the last 48 h. He had a history of AF, ASD, coronary heart disease with stent implantation and diabetes. Physical and laboratory examinations showed no abnormalities. The score of CHA2DS2VASc was 3, and HAS-BLED was 1. Echocardiography revealed a 25-mm secundum ASD. Pulmonary vein (PV) and LAA anatomy were assessed by cardiac computed tomography. PV mapping with 10-pole Lasso catheter was performed following ablation of all four PVs with complete PVI. Following the cryoballoon PVI, the patient underwent LAA occlusion under transesophageal echocardiographic monitoring. Lastly, a 34-mm JIYI ASD occlude device was implanted. A follow-up transesophageal echocardiography at 3 mo showed proper position of both devices and neither thrombi nor leakage was found. CONCLUSION: Sequential cryoballoon PVI and LAA occlusion prior to ASD closure can be performed safely in AF patients with ASD.

Circulating Galectin-3 and Aldosterone for Predicting Atrial Fibrillation Recurrence after Radiofrequency Catheter Ablation.

Background: Circulating galectin-3 (Gal-3) and aldosterone (ALD) are involved in fibrosis and inflammation. However, their potential value as predictors of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) is unknown or controversial. Therefore, the aim of this study was to assess the relationship between baseline Gal-3, ALD levels, and AF recurrence in patients performing RFCA. Methods: 153 consecutive patients undergoing RFCA were included. Gal-3 and ALD were measured at baseline. Univariate and multivariate Cox regressions were performed to determine the predictors of AF recurrence. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) curve were used to assess the value of predictors. Results: There were 35 (22.88%) cases of AF recurrence after RFCA. The recurrence group had significantly higher preoperative serum levels of Gal-3 and ALD than the nonrecurrence group. Univariate and multivariate analysis showed that Gal-3 (HR = 1.28, 95% CI: 1.04-1.56, p = 0.02) and ALD (OR = 1.02, 95% CI: 1.00-1.03, p < 0.03) were significantly associated with AF recurrence after RFCA. The area under the curve (AUC) of preoperative serum Gal-3, ALD, and 2 combined to predict the recurrence of AF patients after RFCA was 0.636, 0.798, and 0.893, respectively, while sensitivity was 65.32%, 71.69%, and 88.61%, respectively and specificity was 77.46%, 78.53%, and 86.0%, respectively. Patients with Gal-3 above the cutoff value of 14.57 pg/ml had higher frequent AF recurrence than the patients with Gal - 3 ≤ 14.57 pg/ml (35% vs. 12%, p < 0.001) during a follow-up. Meanwhile, patients with ALD above the cutoff value of 243.61 pg/ml also had a higher AF recurrence rate than those with ALD ≤ 243.61 pg/ml (37% vs. 11%, p < 0.001) during a follow-up. The recurrence rate in patients with Gal - 3 > 14.57 pg/ml + ALD > 243.61 pg/ml was higher than that in patients with baseline Gal - 3 > 14.57 pg/ml or ALD > 243.61 pg/ml and patients with Gal - 3 ≤ 14.57 pg/ml + ALD ≤ 243.61 pg/ml (57% vs. 14% vs. 9%, p < 0.01, respectively). Conclusion: AF recurrence after RFCA had higher baseline Gal-3 and ALD levels, and higher preoperative circulating Gal-3 and ALD levels were independent predictors of AF recurrence for patients undergoing RFCA, while combination of preoperative Gal-3 and ALD levels has higher prediction accuracy.

Safety and efficacy of different anticoagulation regimens after left atrial appendage occlusion.

BACKGROUND: This study examined the safety and efficacy of different anticoagulation regimens in patients with atrial fibrillation (AF) after left atrial appendage occlusion (LAAC) using the Watchman closure device. METHODS: AF patients who underwent LAAC using the Watchman closure device in the Department of Cardiology, Jiangsu Taizhou People's Hospital between March 2018 and November 2019 were retrospectively enrolled in this study. Patients were divided into two groups according to different postoperative anticoagulant regimens. One group was treated with anticoagulant therapy alone [oral anticoagulant (OAC)/new OAC (NOAC) group] and the other was given NOACs combined with single antiplatelet therapy (SPAT) (NOAC + SAPT group). The incidences of ischemic stroke/transient ischemic attack (TIA), major bleeding events, all-cause mortality, and device-related thrombosis (DRT) were recorded. Furthermore, multivariate regression was used to analyze the factors associated with the occurrence of early DRT. RESULTS: A total of 160 patients, including 42 (51%) females, with a mean age of 69.13±6.14 years were enrolled in this study. The mean CHA2DS2-VASc score was 3.66±1.11 and the mean HAS-BLED score was 4.16±0.82. During the postoperative follow-up period, there were no significant differences in the incidence of ischemic stroke/TIA [hazard ratio (HR) =0.616; 95% confidence interval (CI): 0.056 to 6.818; P=0.693], major bleeding events (HR =0.520; 95% CI: 0.047 to 5.764; P=0.594) nor all-cause mortality (HR =0.579; 95% CI: 0.052 to 6.394; P=0.656) between the two groups. However, the incidence of early DRT was higher in the OAC/NOAC group compared to the NOAC + SAPT group [odds ratio (OR) =0.120; 95% CI: 0.015 to 0.984; P=0.048]. Multivariate regression confirmed that atrial blood stasis (OR =11.367; 95% CI: 1.394 to 92.687; P=0.023) and peri-device leak (OR =9.337; 95% CI: 1.623 to 53.727; P=0.012) were independent predictors of early DRT. CONCLUSIONS: Short-term NOAC + SAPT after LAAC did not significantly increase the incidence of major bleeding events, ischemic stroke/TIA, nor all-cause mortality compared to OAC/NOAC therapy. Not only was NOAC + SAPT therapy found to be safe and effective in short-term follow-up, but it also lowered the risk of early DRT.

MicroRNA-383-5p Regulates Oxidative Stress in Mice with Acute Myocardial Infarction through the AMPK Signaling Pathway via PFKM.

OBJECTIVE: The purpose of this study is to explore the regulating role of microRNA-383-5p (miR-383-5p) in oxidative stress after acute myocardial infarction (AMI) through AMPK pathway via phosphofructokinase muscle-type (PFKM). METHODS: We established the AMI model, and the model mice were injected with miR-383-5p agomir to study the effect of miR-383-5p in AMPK signaling pathways. The target gene for miR-383-5p was reported to be PFKM, so we hypothesized that overexpression of miR-383-5p inhibits activation of the AMPK signaling pathway. RESULTS: In this research, we found that overexpression of miR-383-5p decreases myocardial oxidative stress, myocardial apoptosis, the expression level of PFKM malondialdehyde (MDA), and reactive oxygen species (ROS) in the myocardial tissues after AMI, and finally, AMI-induced cardiac systolic and diastolic function could be improved. CONCLUSION: This study demonstrated that miR-383-5p could reduce the oxidative stress after AMI through AMPK signaling pathway by targeting PFKM.

Mesenchymal stem cell-derived exosomal miR-143-3p suppresses myocardial ischemia-reperfusion injury by regulating autophagy.

AIMS: Myocardial ischemia-reperfusion (I/R) injury is considered as a major obstacle of myocardial perfusion to save acute myocardial infarction, and causes a serious threat to human health. An extensive body of evidence has unveiled that mesenchymal stem cells (MSCs) as adult stem cells play a vital role in the field of damaged myocardial regeneration and repair. However, the biological role of MSCs derived-exosomes in the protection of myocardial I/R injury has not been elucidated. MAIN METHODS: In this study, we isolated and characterized MSCs from the bone marrow of rats femur and tibia. H9c2 cells were administrated to established the cellular hypoxia-reoxygenation (H/R) model, and co-cultured with MSCs and MSCs-derived exosomes. KEY FINDINGS: Functional experiments revealed that MSCs and MSCs-derived exosomes inhibited H/R-induced cell apoptosis and cell autophagy. Interestingly, rapamycin as an activator of autophagy reversed the positive effects of MSCs-derived exosomes, while 3-methyladenine (3-MA) as autophagy inhibitor further promoted the effects of MSCs-derived exosomes, indicating MSCs exerted its function on H/R injury by mediating autophagy. Subsequently, we found that CHK2-Beclin2 pathway participated in H/R-induced autophagy. Mechanistically, miR-143-3p directly targeted CHK2 and negatively regulated CHK2 expression. Moreover, repression of exosomal miR-143-3p promoted H/R-induced autophagy via CHK2-Beclin2 pathway. Consistent with the results of in vitro experiments, in vivo experiments confirmed that exosomal miR-143-3p effectively reduced cell apoptosis by regulating autophagy via CHK2-Beclin2 pathway. SIGNIFICANCE: Collectively, our results indicated that MSCs-derived exosomal miR-143-3p might represent a promising option for the treatment of I/R injury.

The Exosomal lncRNA KLF3-AS1 From Ischemic Cardiomyocytes Mediates IGF-1 Secretion by MSCs to Rescue Myocardial Ischemia-Reperfusion Injury.

The purpose of the study was to explore the mechanism by which myocardial ischemia-reperfusion (I/R) injury-induced exosomes modulate mesenchymal stem cells (MSCs) to regulate myocardial injury. In this study, we established an I/R injury model in vivo and a hypoxia-reoxygenation (H/R) model in vitro. Then, exosomes isolated from H/R-exposed H9c2 cells were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot analysis. CCK-8 assays and flow cytometry were performed to assess cell injury. ELISA was applied to determine the level of insulin-like growth factor 1 (IGF-1). Echocardiography was used to assess cardiac function in vivo. HE staining and TUNEL assays were conducted to analyze myocardial injury in vivo. In the present study, H/R-exposed H9c2 cells induced IGF-1 secretion from MSCs to inhibit cell myocardial injury. Moreover, exosomes derived from H/R-exposed H9c2 cells were introduced to MSCs to increase IGF-1 levels. The lncRNA KLF3-AS1 was dramatically upregulated in exosomes derived from H/R-treated H9c2 cells. Functional experiments showed that the exosomal lncRNA KLF3-AS1 promoted IGF-1 secretion from MSCs and increased H9c2 cell viability. In addition, miR-23c contains potential binding sites for both KLF3-AS1 and STAT5B, and miR-23c directly bound to the 3'-UTRs of KLF3-AS1 and STAT5B. Furthermore, the lncRNA KLF3-AS1 promoted IGF-1 secretion from MSCs and rescued myocardial cell injury in vivo and in vitro by upregulating STAT5B expression. The lncRNA KLF3-AS1 may serve as a new direction for the treatment of myocardial I/R injury.