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.

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.

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.

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.

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.

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.

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.

miR-15a-5p regulates myocardial fibrosis in atrial fibrillation by targeting Smad7.

BACKGROUND: At present, there is no effective treatment for myocardial fibrosis in atrial fibrillation (AF). It is reported that miR-15a-5p is abnormally expressed in AF patients but its specific role remains unclear. This study aims to investigate the effect of miR-15a-5p in myocardial fibrosis. METHODS: Left atrial appendage (LAA) tissues were collected from AF and non-AF patients. In lipopolysaccharide (LPS) stimulated H9C2 cells, miR-15a-5p mimic, inhibitor, pcDNA3.1-Smad7 and small interfering RNA-Smad7 (siRNA-Smad7) were respectively transfected to up-regulate or down-regulate the intracellular expression levels of miR-15a-5p and Smad7. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) were used to determine the expression levels of miR-15a-5p, Smad7, transforming growth factor ß1 (TGF-ß1) and collagen I. Cell counting kit-8 (CCK-8) and ethylene deoxyuridine (EdU) were used to determine cell viability and proliferation capacity, respectively. Dual-luciferase was used to detect whether miR-15a-5p interacted with Smad7, hydroxyproline (HYP) and Hematoxylin-Eosin (HE) staining were used to detect tissue fibrosis. RESULTS: The expression levels of miR-15a-5p, TGF-ß1 and collagen I were up-regulated, while Smad7 was down-regulated in AF tissues and LPS-stimulated cells. MiR-15a-5p mimic can inhibit the expression of Smad7, and the dual-luciferase experiment confirmed their interaction. MiR-15a-5p inhibitor or pcDNA3.1-Smad7 can inhibit LPS-induced fibrosis and cell proliferation, while siRNA-Smad7 can reverse the changes caused by miR-15a-5p inhibitor. CONCLUSION: We combined clinical studies with LPS-stimulated H9C2 cell model to validate the role of miR-15a-5p in the regulation of Smad7 and fibrosis. Taken together, the miR-15a-5p/Smad7 pathway might be a potential target for AF therapy.

Identification of Circulating lncRNA Expression Profiles in Patients with Atrial Fibrillation.

PURPOSE: To investigate the expression profiles of long noncoding RNAs (lncRNAs) in patients with atrial fibrillation (AF). METHODS: The peripheral blood monocytes of a total of 20 patients with AF and 20 healthy subjects were collected for gene chip technology to detect differentially expressed lncRNAs from 2017.01 to 2017.08. Reverse transcription polymerase chain reaction (RT-PCR) was applied for further verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the functions of differentially expressed genes and related pathways. RESULTS: There were 19 lncRNAs differentially expressed (FC ≥ 2, P < 0.05), of which 6 were upregulated and 13 were downregulated. Two of three upregulated lncRNAs (P = 0.014 and 0.006 for HNRNPU-AS1 and LINC00861, respectively) and two of three downregulated lncRNAs (P = 0.028 and 0.032 for RP11-443B7.3 and CTD-2616J11.14, respectively) were randomly confirmed by RT-PCR and showed a significantly different expression with the RNA-seq results. GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in metabolic process, catabolic process, and biosynthetic process. Differentially expressed transcripts in cellular component were mainly involved in nuclear lumen, organelle lumen, and cytoplasm. Differentially expressed transcripts in molecular function were mainly involved in protein binding, RNA binding, and molecular function. KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed lncRNAs include calcium signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway. HNRNPU-AS1 was the highest positive correlated lncRNA in the networks. CONCLUSIONS: The expression of lncRNA in peripheral blood of AF patients is different from that of normal people. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide experimental basis and new therapeutic target for prognosis and treatment of patients with AF. HNRNPU-AS1 may play an important role in the pathophysiology and mechanisms of AF.

Integrative analysis of the circRNA-miRNA regulatory network in atrial fibrillation.

We aimed to investigate the circRNA-miRNA regulatory network in atrial fibrillation (AF) by using Cytoscape and HMDD v3.0. Finally, 120 differentially expressed circRNAs in peripheral blood monocytes of 4 AF patients were preliminarily screened by circRNA microarray. circRNA_4648, circRNA_4631, and circRNA_2875 were the first four circRNAs with the most binding nodes in the circRNA-miRNA network. The top three most frequent miRNAs for up-regulated circRNAs were hsa-miR-328 that interacted with 5 up-regulated circRNAs, hsa-miR-4685-5p with 4 up-regulated circRNAs, hsa-miR-3150a-3p, hsa-miR-4649-5p, hsa-miR-4783-3p, and hsa-miR-8073 with 3 up-regulated circRNAs,, while the top three most frequent miRNAs for down-regulated circRNAs were hsa-miR-328 that interacted with 14 down-regulated circRNAs, hsa-miR-4685-5p with 11 down-regulated circRNAs and hsa-miR-661 with 9 down-regulated circRNAs. According to HMDD v3.0, five up-regulated and eleven down-regulated circRNAs were found to interact with AF related miRNAs. These results indicated the possible regulatory network between circRNAs and miRNAs in the pathogenesis of AF.

Genome-wide analysis of circular RNA expression profiles in patients with atrial fibrillation.

Atrial fibrillation (AF) is one of the most common clinical cardiac arrhythmias. This study was done to screen differentially expressed circular RNAs (circRNAs) in human monocytes from patients with AF and healthy controls using microarray, and preliminarily explore the role of circRNAs in the development of AF. The expression of circRNAs in peripheral blood monocytes of 4 AF patients and 4 healthy donors was detected by chip technology and validated by qRT-PCR. Differentially expressed genes were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the function of differentially expressed genes and related pathways. Potential connections between circRNAs and miRNAs were explored by using Cytoscape. 120 differentially expressed circRNAs (FC≥2, P<0.05) were preliminarily screened by circRNA microarray, of which 65 were up-regulated and 55 down-regulated. All of 4 upregulated circRNAs (circRNA_0031, circRNA_1837, circRNA_5901 and circRNA_7571) and 3 out of 4 downregulated circRNAs (circRNA_5801, circRNA_7386 and circRNA_7577) were randomly confirmed by RT-PCR. GO and KEGG analysis suggested that differentially expressed circRNA-related genes are mainly involved in inflammation, immunity, and signaling transduction. CircRNA_7571, circRNA_4648, circRNA_4631 and circRNA_2875 were the first 4 circRNAs with the most binding nodes in the co-expression network. In addition, hsa-miR-328 was the highest positively correlated miRNA in the networks. Our findings demonstrated that there were differentially expressed circRNAs in human monocytes from AF patients. circRNA_7571, circRNA_4648, circRNA_4631 and circRNA_2875 were the first 4 circRNAs with the most binding nodes in the co-expression network. hsa-miR-328 was the largest node that interacted with circRNAs in the co-expression network. circRNAs-hsa-miR-328 network may play a critical role in the pathophysiology and mechanism of AF.

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.

Expression profile of long non-coding RNAs during the differentiation of human umbilical cord derived mesenchymal stem cells into cardiomyocyte-like cells.

We aimed to investigate the differentially expressed long non-coding RNAs (lncRNAs) during the differentiation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) into cardiomyocyte-like cells induced by 5-aza. hUCMSCs were isolated and purified from umbilical cords. After treated with 10 µmol/L 5-Aza for 24 h, hUCMSCs wereas continued to be cultured for 14 days. Comparison of cardiac specific genes and the expression profile of lncRNAs on hUCMSCs between day 14 and day 0 was performed using immunofluorescence staining, immunohistochemistry, Western blot assay, RT-PCR and lncRNA microarray. Results show that well-organized sarcomeric structure and more cTnI and MLC2a staining were seen in hUCMSCs of day 14 after 5-aza-induced compared to those in day 0. Expression of Desmin, Nkx2.5, cTnI and MLC2a of hUCMSCs was much higher on day 14 compared with day 0 (P < 0.01). 41 differentially expressed lncRNAs were found on day 14 hUCMSCs compared those of day 0 were identified. Among them, 25 upregulated and 16 downregulated. Four out of the five upregulated lncRNAs (P = 0.00035, 0.014, 0.016 and 0.005 for uc010vei.1, X72487, BC064139, AK092074) and four out of the five downregulated lncRNAs (P = 0.038, 0.0014, 0.00026 and 0.004 for X85157, uc007keu.1, AK309872, NR_029399) showed significantly different expressions in further validation using RT-PCR. Our results illustrated that there was a dysregulation of the lncRNA profile during the differentiation of hUCMSCs into cardiomyocyte-like cells, which will provide the foundation for further study of the biological functions and mechanism of lncRNAs in the differentiation of hUCMSCs into cardiomyocyte-like cells.

Prediction efficiency of serum cystatin C for clinical outcome in patients with cardiac resynchronization therapy.

BACKGROUND: Since only 60-70% of select patients with chronic heart failure (CHF) are responders in cardiac resynchronization therapy (CRT), this study aimed to investigate whether serum cystatin C (Cys C) can be used to evaluate the effectiveness of CRT in patients with CHF. METHODS: Seventy-six patients implanted with CRT were retrospectively enrolled. The concentration of serum Cys C was detected and echocardiography was performed before and after 15 days, 1 month, and 6 months of CRT. RESULTS: There were 52 patients (68.4%) who responded to CRT during the follow-up. In the responding group, compared with the pre-CRT, the cardiac function, QRS interval, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were significantly improved at 6 months after implantation (P < 0.05), but the level of serum Cys C decreased significantly from 1 month after CRT. There was no change of all the parameters in the non-responding group during the follow-up. In the responding group, the ΔCys C% is significantly related to the ΔLVEDV%, ΔLVESV%, and ΔLVEF%. Multivariate linear analysis shows that the ΔCys C% is significantly related to the ΔLVEDV%. The level of serum Cys C before CRT implantation could predict the response to CRT (AUC = 0.78, P < 0.05). Univariate analysis and multivariate analysis demonstrated that the level of Cys C remained independent predictor for CRT (P = 0.028, 95% CI 0.919-1.348). CONCLUSIONS: The level of serum Cys C before CRT implantation is valuable in predicting the response to CRT.

Inhibitor of p53-p21 pathway induces the differentiation of human umbilical cord derived mesenchymal stem cells into cardiomyogenic cells.

P53 is shown recently to play an important role in the proliferation and differentiation of mesenchymal stem cells. In this study, human umbilical cord derived mesenchymal stem cells (hUCMSCs) were isolated and purified from the umbilical cords of normal or cesarean term deliveries, after treatment with 20 µmol/L PFT-α for 24 h, hUCMSCs were continued to be cultured for 4 weeks, cardiac-specific protein expression of cTnI, Desmin and Nkx2.5 was determined using immunofluorescence assay and RT-PCR. The expression of p53 and p21 was detected by western blot. Results showed that no expression of cTnI, Desmin or Nkx2.5 was observed in the control and the PFT-α group at 1 week after induction. However, after 4 weeks, while control group still had little expression of cTnI, Desmin and Nkx2.5, the PFT-α group demonstrated strong expression of cTnI, Desmin and Nkx2.5 (P < 0.001). At 4 weeks after induction, differentiation rate of cardiomyogenic cells in the PFT-α group (36.98 %) was significantly higher than that in the control group (4.41 %) (P < 0.01). Western blot analysis show that downregulation of p53 and p21 was seen in the PFT-α group at 4 weeks. The difference compared with the control group was statistically significant (P < 0.01). In conclusion, PFT-α can promote the differentiation of hUCMSCs into cardiomyogenic cells by modulating the p53-p21 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.

Karyotype stability of human umbilical cord-derived mesenchymal stem cells during in vitro culture.

The aim of this study was to investigate whether the chromosomes of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) change following in vitro culture for several generations. In the present study, umbilical cords from two healthy infants following cesarean delivery were collected aseptically and hUCMSCs were isolated by digestion with collagenase and trypsin, and then cultured in vitro. hUCMSCs with fibroblastic morphology were presented from the human umbilical cord tissue after 7 days of adherent culture. When cultured for 6 passages in vitro, the hUCMSCs maintained a stable spindle-shaped morphology. Cells reached the logarithmic growth phase after 3-4 days of culture. In addition, CD13, CD29, CD44, CD90 and CD105 were highly expressed in generations P3-P6. The expression of CD31, CD34, CD45 and HLA-DR was negative. Furthermore, karyotype analysis revealed a normal diploid karyotype with 46 chromosomes and no abnormal changes were found in chromosome structure. These findings suggest that when cultured for 6 passages in vitro, hUCMSCs maintain a stable immunophenotype and chromosome structure, which provides an experimental basis for the safety of hUCMSC cytotherapy.

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.