Alteration of the gut microbiome in patients with heart failure: A systematic review and meta-analysis.

Recent research has revealed that alterations of the gut microbiome (GM) play a comprehensive role in the pathophysiology of HF. However, findings in this field remain controversial. In this study, we focus on differences in GM diversity and abundance between HF patients and non-HF people, based on previous 16 S ribosomal RNA (16rRNA) gene sequencing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search of PubMed, Web of Science, Embase, Cochrane Library, and Ovid databases using the keyword "Heart failure" and "Gastrointestinal Microbiome". A significant decrease in alpha diversity was observed in the HF patients (Chao1, I2 = 87.5 %, p < 0.001; Shannon index, I2 = 62.8 %, p = 0.021). At the phylum level, the HF group exhibited higher abundances of Proteobacteria (I2 = 92.0 %, p = 0.004) and Actinobacteria (I2 = 82.5 %, p = 0.010), while Bacteroidetes (I2 = 45.1 %, p = 0.017) and F/B ratio (I2 = 0.0 %, p＜0.001) were lower. The Firmicutes showed a decreasing trend but did not reach statistical significance (I2 = 82.3 %, p = 0.127). At the genus level, the relative abundances of Streptococcus, Bacteroides, Alistipes, Bifidobacterium, Escherichia-Shigella, Enterococcus and Klebsiella were increased in the HF group, whereas Ruminococcus, Faecalibacterium, Dorea and Megamona exhibited decreased relative abundances. Dialister, Blautia and Prevotella showed decreasing trends but without statistical significance. This observational meta-analysis suggests that GM changes are associated with HF, manifesting as alterations in GM abundance, disruptions in the production of short-chain fatty acids (SCFAs) bacteria, and an increase in trimethylamine N-oxide (TMAO) producing bacteria.

A Simple Score to Predict New-onset Atrial Fibrillation After Ablation of Typical Atrial Flutter.

BACKGROUND: New-onset atrial fibrillation (NeAF) is common after cavotricuspid isthmus-dependent counterclockwise atrial flutter (CCW-AFL) ablation. This study aimed to investigate a simple predictive model of NeAF after CCW-AFL ablation. METHODS: From January 2013 to December 2017, consecutive patients receiving CCW-AFL ablation were enrolled from three centers. Clinical, echocardiographic, and electrocardiographic data were collected and followed. Patients from two centers and another center were assigned into the derivation and validation cohorts, respectively. In the derivation cohort, logistic regression was performed to evaluate the ability of parameters to discriminate those with and without NeAF. A score system was developed and then validated. RESULTS: Two hundred seventy-one patients (mean 59.7±13.6 age; 205 male) were analyzed. During follow-up (73.0±6.5 months), 107 patients (39.5%) had NeAF. 190 and 81 patients were detected in the derivation and validation cohorts, respectively. Hypertension, age ≥70 years, left atrial diameter ≥42 mm, P wave duration ≥120 ms and the negative component of flutter wave in lead II ≥120 ms were selected as the final parameters. A weighted score was used to develop the HAD-AF score ranging from 0 to 9. In the derivation cohort, area under the receiver operating characteristic curve (AUC) was 0.938 (95% CI 0.902-0.974), superior to those of currently used CHA2DS2-VASC (0.679, 95% CI 0.600-0.757) and HATCH scores (0.651, 95% CI 0.571-0.730) (P<0.001). Performance maintained in the validation cohort. CONCLUSIONS: 39.5% of patients developed NeAF in 6 years after CCW-AFL ablation. HAD-AF score can reliably identify patients likely to develop NeAF after CCW-AFL ablation.

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.

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.

Arrhythmogenesis of surgical atrial incisions and lesions in Maze procedure: insights from high-resolution mapping of atrial tachycardias.

BACKGROUND: Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. METHODS AND RESULTS: We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. CONCLUSIONS: Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.

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.

Low-Voltage Area at the Anterior Wall of the Left Atrium Is Associated With Thromboembolism in Atrial Fibrillation Patients With a Low CHA2DS2-VA Score.

Background: Non-valvular atrial fibrillation (NVAF) in patients at low risk of thromboembolism (TE) does not mean "no risk." We sought to assess the risk factors associated with TE in clinically low-risk AF patients with a non-gender CHA2DS2 -VASc score (CHA2DS2-VA score) of 0 or 1. Methods: In this single-center cross-sectional study, NVAF patients with a CHA2D-VA score of 0 or 1 who underwent index high-density bipolar voltage mapping of the left atrium (LA) and AF ablation were consecutively enrolled from 2017 to 2020. The population was divided into patients with and without TE history before voltage mapping. AF patients with CHA2DS2-VA score of 0 to 1 before TE (TE group) were analyzed and compared with clinically low-risk AF patients without TE history (non-TE group). The association among LA low voltage area (LVA), other clinical factors and TE history was analyzed with logistic regression. Results: In the TE group, LVA was more prevalent [15/25 (60%) vs. 105/359 (29.2%), p = 0.003] and more preferentially located at the anterior wall [8/15 (53%) vs. 24/105 (23%), p = 0.025]. Among patients with LVA, the activation time from the sinus node to the left atrial appendage was significantly longer in the TE group (77.09 ± 21.09 vs. 57.59 ± 15.19 ms, p < 0.001). Multivariate analysis demonstrated that LVA at the anterior wall of the LA [OR: 4.17 (95% CI: 1.51 to 11.51); p = 0.006] and being female [OR: 3.40 (95% CI: 1.36 to 8.51); p = 0.009] were associated with TE history. Conclusions: LVA at the anterior wall of the LA is associated with TE history in NVAF patients with a low CHA2DS2-VA score.

Biological denitrification in an anoxic sequencing batch biofilm reactor: Performance evaluation, nitrous oxide emission and microbial community.

The present study evaluated the performance of biological denitrification in an anoxic sequencing batch biofilm reactor (ASBBR) and its nitrous oxide (N2O) emission. After 90 days operation, the effluent chemical oxygen demand and total nitrogen removal efficiencies high of 94.8% and 95.0%, respectively. Both polysaccharides and protein contents were reduced in bound EPS (TB-EPS) and loosely bound EPS (LB-EPS) after biofilm formation. According to typical cycle, N2O release rate was related to the free nitrous acid (FNA) concentration with the maximum value of 3.88 µg/min and total conversion rate of 1.27%. Two components were identified from EEM-PARAFAC model in soluble microbial products (SMP). Protein-like substances for component 1 changed significantly in denitrification process, whereas humic-like and fulvic acid-like substances for component 2 remained relatively stable. High-throughput sequencing results showed that Lysobacter, Tolumonas and Thauera were the dominant genera, indicating the co-existence of autotrophic and heterotrophic denitrifiers in ASBBR.

LncRNA-uc.167 influences cell proliferation, apoptosis and differentiation of P19 cells by regulating Mef2c.

In our previous study we screened thousands of lncRNAs for their relationship with ventricular septal defect. Among these lncRNAs, uc.167 attracted our attention for its high level of conservation and that it was antisense to the Mef2c gene, which encodes myocyte enhancer factor 2C. This study aims to investigate the role of uc.167 during cardiomyocyte maturation in P19 cells induction and possible mechanism. The uc.167 expression level in human heart tissue of ventricular septum defect (VSD) was evaluated by qRT-PCR. The UCSC database was searched to investigate the bioinformatics of uc.167. We constructed overexpression vector of uc.167 and Mef2c. To detect proliferation and apoptosis, we combined cell cycle analysis and CCK8, Hoechst staining, flow cytometry and caspase-3 assays, respectively. The cardiomyogenesis related RNAs (cTnT, GATA4, and Mef2c) and proteins were detected by qRT-PCR and Western blotting. In this study, we found that uc.167 expression was significantly increased in VSD heart tissues. uc.167 is on the opposite strand to the coding gene Mef2c. The expression model of Mef2c and uc.167 showed an opposite correlation in the embryonic development and process of differentiation of P19 cells into cardiomyocytes. Overexpression of uc.167 inhibited proliferation but promoted apoptosis in P19 cells compared with the vector group, and those relative mRNAs and proteins decreased during the differentiation process. Whereas, co-expression of Mef2c and uc.167 can partially reverse the negative effects of uc.167 on proliferation, apoptosis and differentiation. Taken together, our findings suggest that uc.167 contributes to the development potential of VSD and may constitute a potential therapeutic target in this disease. uc.167 influences cell proliferation, apoptosis and differentiation of P19 cell by regulating Mef2c.

The ER stress-mediated mitochondrial apoptotic pathway and MAPKs modulate tachypacing-induced apoptosis in HL-1 atrial myocytes.

BACKGROUND AND OBJECT: Cell apoptosis is a contributing factor in the initiation, progression and relapse of atrial fibrillation (AF), a life-threatening illness accompanied with stroke and heart failure. However, the regulatory cascade of apoptosis is intricate and remains unidentified, especially in the setting of AF. The aim of this study was to explore the roles of endoplasmic reticulum (ER) stress, mitochondrial apoptotic pathway (MAP), mitogen-activated protein kinases (MAPKs), and their cross-talking in tachypacing-induced apoptosis. METHODS AND RESULTS: HL-1 cells were cultured in the presence of tachypacing for 24 h to simulate atrial tachycardia remodeling. Results showed that tachypacing reduced cell viability measured by the cell counting kit-8, dissipated mitochondrial membrane potential detected by JC-1 staining and resulted in approximately 50% apoptosis examined by Hoechst staining and annexin V/propidium iodide staining. In addition, the proteins involved in ER stress, MAP and MAPKs were universally up-regulated or activated via phosphorylation, as confirmed by western blotting; and reversely silencing of ER stress, caspase-3 (the ultimate executor of MAP) and MAPKs with specific inhibitors prior to pacing partially alleviated apoptosis. An inhibitor of ER stress was applied to further investigate the responses of mitochondria and MAPKs to ER stress, and results indicated that suppression of ER stress comprehensively but incompletely attenuated the activation of MAP and MAPKs aroused by tachypacing, with the exception of ERK1/2, one branch of MAPKs. CONCLUSIONS: Our study suggested tachypacing-induced apoptosis is regulated by ER stress-mediated MAP and MAPKs. Thus, the above three components are all promising anti-apoptotic targets in AF patients and ER stress appears to play a dominant role due to its comprehensive effects.