Effects of glucagon-like peptide-1 receptor agonists on major coronary events in patients with type 2 diabetes.

AIMS: In patients suffering from type 2 diabetes mellitus (T2DM), the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) treatment on major coronary events, including myocardial infarction (MI), unstable angina and coronary revascularization, is unclear. We performed a meta-analysis to assess the benefits of GLP-1RAs for major coronary events. MATERIALS AND METHODS: We systematically searched the PubMed, CENTRAL, EMBASE, and clinicaltrial.gov databases to seek eligible studies with a cardiovascular endpoint comparing GLP-1RAs with a placebo in T2DM patients. Odds ratio (OR) and 95% confidence interval (CI) were calculated for the outcomes. RESULTS: Nine studies, with a total of 64236 patients, were conducted. GLP-1RA treatment reduced fatal and non-fatal MI by 8% (OR 0.92, 95% CI 0.86-0.99; P = 0.02; I2 = 39%). Further, the reduction reached 15% in human-based GLP-1RA treated patients. Similarly, Once-weekly GLP-1RA treatment reduced the risk of MI by 13%. In contrast, GLP-1RA treatment did not reduce the risk of hospitalization for unstable angina (OR 1.11, 95% CI 0.97-1.28; P = 0.13; I2 = 21%). GLP-1RAs exhibited a tendency to lower the risk of coronary revascularization (OR 0.95, 95% CI 0.89-1.02，P = 0.15，I2 = 22%), but without statistical significance. However, human-based GLP-1RAs decreased the risk by 11%. CONCLUSIONS: In high-risk patients suffering from T2DM, GLP-1RAs were associated with a decrease in MI, especially the human-based and once-weekly GLP-1RAs. No benefit was seen for hospitalization for unstable angina or coronary revascularization. Further research is urgently needed to ascertain improvements in coronary events. This article is protected by copyright. All rights reserved.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Diastolic Blood Pressure and Intensive Blood Pressure Control on Cognitive Outcomes: Insights From the SPRINT MIND Trial.

BACKGROUND: The potential benefits or harms of intensive systolic blood pressure (BP) control on cognitive function and cerebral blood flow in individuals with low diastolic blood pressure (DBP) remain unclear. METHODS: We conducted a post hoc analysis of the SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension) that randomly assigned hypertensive participants to an intensive (<120 mm Hg; n=4278) or standard (<140 mm Hg; n=4385) systolic blood pressure target. We evaluated the effects of BP intervention on cognitive outcomes and cerebral blood flow across baseline DBP quartiles. RESULTS: Participants in the intensive group had a lower incidence rate of probable dementia or mild cognitive impairment than those in the standard group, regardless of DBP quartiles. The hazard ratio of intensive versus standard target for probable dementia or mild cognitive impairment was 0.91 (95% CI, 0.73-1.12) in the lowest DBP quartile and 0.70 (95% CI, 0.48-1.02) in the highest DBP quartile, respectively, with an interaction P value of 0.24. Similar results were found for probable dementia (interaction P=0.06) and mild cognitive impairment (interaction P=0.80). The effect of intensive treatment on cerebral blood flow was not modified by baseline DBP either (interaction P=0.25). Even among participants within the lowest DBP quartile, intensive versus standard BP treatment resulted in an increasing trend of annualized change in cerebral blood flow (+0.26 [95% CI, -0.72 to 1.24] mL/[100 g·min]). CONCLUSIONS: Intensive BP control did not appear to have a detrimental effect on cognitive outcomes and cerebral perfusion in patients with low baseline DBP. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.

The adjunctive effect for left pulmonary vein isolation of vein of Marshall ethanol infusion in persistent atrial fibrillation.

OBJECTIVE: This study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF). METHODS AND RESULTS: A total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM. CONCLUSION: EIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.

Fascicular ventricular tachycardia arising from the left side His and its adjacent region: a subset of upper septal idiopathic left ventricular tachycardia.

AIMS: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics. METHODS AND RESULTS: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences. CONCLUSIONS: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region.

Revisiting the characteristics and ablation strategy of biatrial tachycardias: a case series and systematic review.

AIMS: To describe the role of left atrial (LA) epicardial conduction and targets of ablation in biatrial tachycardias (BiATs). METHODS AND RESULTS: Consecutive patients with BiAT diagnosed by high-density mapping and appropriate entrainment were enrolled. A systematic review of case reports or series was then performed. Biatrial tachycardia was identified in 20 patients aged 63.5 ± 11.1 years. Among them, eight had LA epicardial conduction, including four via the ligament of Marshall, two via myocardial fibres between the great cardiac vein (GCV) and LA, one via septopulmonary bundle, and one via myocardial fibres between the posterior wall and coronary sinus. Ablation was targeted at the anatomical isthmus in 14, including 5 undergoing vein of Marshall ethanol infusion and 2 undergoing ablation in the GCV. Another six underwent ablation at interatrial connections, including one with septopulmonary bundle at the fossa ovalis and five at the atrial insertions of Bachmann's bundle. After a mean follow-up of 8.7 ± 3.8 months, five patients had recurrence of atrial fibrillation/flutter. Systematic review enrolled 87 patients in previous and the present reports, showing a higher risk of impairment in atrial physiology in those targeting interatrial connections (30.4 vs. 5.0%, P < 0.001) but no significant difference in short- and long-term effectiveness. CONCLUSION: Left atrial epicardial conduction is common in BiATs and affects the ablation strategy. Atrial physiology is a major concern in selecting the target of intervention.

Vein of Marshall ethanol infusion: First-step or adjunctive choice for perimitral atrial tachycardia?

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.

Direct autotransfusion in the management of acute pericardial tamponade during catheter ablation for atrial fibrillation: An imperfect but practical method.

Background: Acute pericardial tamponade (APT) is one of the most serious complications of catheter ablation for atrial fibrillation (AF-CA). Direct autotransfusion (DAT) is a method of reinjecting pericardial blood directly into patients through vein access without a cell-salvage system. Data regarding DAT for APT are rare and provide limited information. Our present study aims to further investigate the safety and feasibility of DAT in the management of APT during the AF-CA procedure. Methods and results: We retrospectively reviewed 73 cases of APT in the perioperative period of AF-CA from January 2014 to October 2021 at our institution, among whom 46 were treated with DAT. All included patients successfully received emergency pericardiocentesis through subxiphoid access guided by X-ray. Larger volumes of aspirated pericardial blood (658.4 ± 545.2 vs. 521.2 ± 464.9 ml), higher rates of bridging anticoagulation (67.4 vs. 37.0%), and surgical repair (6 vs. 0) were observed in patients with DAT than without. Moreover, patients with DAT were less likely to complete AF-CA procedures (32/46 vs. 25/27) and had a lower incidence of APT first presented in the ward (delayed presentation) (8/46 vs. 9/27). There was no difference in major adverse events (death/disseminated intravascular coagulation/multiple organ dysfunction syndrome and clinical thrombosis) (0/0/1/0 vs. 1/0/0/0), other potential DAT-related complications (fever/infection and deep venous thrombosis) (8/5/2 vs. 5/3/1), and length of hospital stay (11.4 ± 11.6 vs. 8.3 ± 4.7 d) between two groups. Conclusion: DAT could be a feasible and safe method to deal with APT during AF-CA procedure.

Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

Expression profile analysis of long noncoding RNA and messenger RNA during mouse cementoblast mineralization.

BACKGROUND AND OBJECTIVE: Emerging evidence has uncovered that long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) exert biofunctions on cellular mineralization and bone formation. In this study, we aimed to identify lncRNA-mRNA expression profiles and expression patterns, and explore their underlying biofunctions during cementoblast mineralization. MATERIALS AND METHODS: Cementoblasts were cultured in mineralized medium for 0, 7, and 14 days. We used quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) to detect expression levels of osteocalcin (OCN), bone sialoprotein (BSP), and Osterix (Osx). Alkaline phosphatase (ALP) staining and alizarin red staining (ARS) were conducted to detect ALP activity and number of mineralized nodule. Total RNA was extracted from cells and used for high-throughput sequencing. EBSeq package was applied to analyze differentially expressed genes. Mfuzz R package was used to identify gene expression patterns. The weighted gene co-expression network analysis (WGCNA) was performed to explore co-expressed mRNAs of differentially expressed lncRNAs (DElncRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were adopted by Clusterprofile R package. RESULTS: Cementoblasts were successfully induced by osteogenic medium. Compared with those on day 0, 384 DElncRNAs and 4255 differentially expressed mRNAs (DEmRNAs), respectively, were found on day 7. Meanwhile, 645 DElncRNAs and 4717 DEmRNAs were detected on day 14. Both DElncRNAs and DEmRNAs were classified into six clusters with different expression patterns. DEmRNAs and co-expressed mRNA of DElncRNAs were predominantly related to cell process, binding, phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and hippo signaling pathway. CONCLUSION: The results demonstrated that both noncoding and coding RNAs were involved in the process of mineralization in cementoblasts, which may provide a new database for further study.

Repeat ablation strategy for recurrent persistent atrial fibrillation: A propensity-matched score comparison between "2C3L" and "extensive ablation" approach.

BACKGROUND: Debates exist in the repeat ablation strategy for patients with recurrence presenting as persistent atrial fibrillation (AF) after initial persistent AF ablation. OBJECTIVE: To compare the outcome between the "2C3L" and "extensive ablation" approach in patients undergoing repeat procedures for recurrent persistent AF. METHODS: Propensity-score matching was performed in 196 patients with AF recurrence undergoing repeat ablation, and 79 patients treated with "2C3L" strategy were matched to 79 patients treated with "extensive ablation" strategy. The "2C3L" approach included pulmonary vein isolation, mitral isthmus, left atrial roof, and cavotricuspid isthmus ablation, while the "extensive ablation" strategy included extensive ablation of a variety of other targets aiming to terminate the AF. The primary outcome was freedom from any atrial tachyarrhythmia after 24-h ambulatory monitoring follow-up for 12 months. RESULTS: No statistically significant difference was found between the primary outcome between the "2C3L" and the "extensive ablation" group [70.9% vs. 69.6%, p = .862; 95% confidence interval (CI) -12.8 to 15.3], although the "extensive ablation" group had a significantly high proportion of AF termination (19.0% for "2C3L" vs. 41.8% for "extensive ablation" group, p = .002; 95% CI 8.5-35.9). And AF termination was not related to the primary outcome in multifactorial regression. At 40 ± 22 months after the repeat procedure, the primary outcome was also comparable (57.0 % for "2C3L" vs. 48.1% for "extensive ablation" group, p = .265; 95% CI -6.6 to 23.7). CONCLUSION: The outcome between the "2C3L" and "extensive ablation" approaches was comparable in patients undergoing repeat procedures for recurrent persistent AF.

Multimorbidity, polypharmacy and inappropriate prescribing in elderly patients with atrial fibrillation: A report from the China Atrial Fibrillation Registry Study.

Background: Multimorbidity, polypharmacy and inappropriate prescribing is common in elderly patients worldwide. We aimed to explore the current status of multimorbidity, polypharmacy and the appropriateness of pharmacological therapy among elderly patients with atrial fibrillation (AF) in China. Materials and methods: We randomly selected 500 patients aged 65 years or older from the China AF Registry study. Multimorbidity was defined as ≥2 comorbidities and polypharmacy was defined as ≥5 long-term prescribed drugs. Appropriateness of prescribing was evaluated using the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria version 2. Patients' attitudes toward polypharmacy were evaluated by the Patients' Attitudes Towards Deprescribing (PATD) questionnaire. Results: Among the 500 patients included (mean age 75.2 ± 6.7 years, 49.0% male), 98.0% had multimorbidity and 49.4% had polypharmacy. The prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) was 43.6% (n = 218) and 71.6% (n = 358), respectively. Traditional Chinese medicine attributed largely to PIMs. Anticoagulants were the most common PPOs. Many clinical factors increased the risk of PIMs and PPOs. However, polypharmacy increased the risk of PIMs (OR 2.70, 95%CI 1.78-4.11; p < 0.0001), but not PPOs. In addition, 73.7% patients with polypharmacy were willing to have one or more of their medications prescribed if advised by their doctor. Conclusion: Multimorbidity and polypharmacy were highly prevalent in elderly patients with AF in China. A high prevalence of inappropriate prescribing was also observed. Therefore, much more attention should be paid to the serious health problem in the elderly population.

Effect of repeat catheter ablation vs. antiarrhythmic drug therapy among patients with recurrent atrial tachycardia/atrial fibrillation after atrial fibrillation catheter ablation: data from CHINA-AF registry.

AIMS: Although several studies have proved that repeat catheter ablation is beneficial to recurrent atrial tachycardia (AT)/atrial fibrillation (AF) after AF catheter ablation, the hard endpoints of the effect of catheter ablation on recurrent AT/AF patients after AF catheter ablation remains unclear. Our study aims to compare the effect of catheter ablation and drug therapy on recurrent AT/AF patients after AF catheter ablation. METHODS AND RESULTS: Four thousand nine hundred and thirteen consecutive patients with recurrent AT/AF after catheter ablation from the China-AF registry were enrolled. The patients were divided into two study groups: the repeat catheter ablation group and the medical therapy group. The primary endpoint is a composite of cardiovascular mortality or ischaemic stroke or major bleeding events. Secondary endpoints were each component of the primary endpoints and AF recurrence rate. Landmark analysis and Cox regression were used in the statistical analysis. We chose landmark 36 months as the primary landmark date. Over a median follow-up period of 40 ± 24 months, 4913 patients were divided into either the repeat ablation group or the medical therapy group. The cumulative incidence of the composite primary outcome was significantly lower in the repeat ablation group than the medical therapy group (adjusted hazard ratio = 0.56; 95% confidence interval: 0.35-0.89; P = 0.015) of landmark 36 months (2359 patients were included in medical therapy group and 704 patients were included in repeat ablation group at landmark 36 months). However, all secondary endpoints were not statistically different in the two groups, including cardiovascular mortality, ischaemic stroke, major bleeding events, and AF recurrence rate. CONCLUSION: Based on this research, in recurrent AT/AF patients after a catheter ablation procedure, compared with medical therapy, repeat catheter ablation may significantly reduce the risk of the endpoint of composite cardiovascular mortality, ischaemic stroke, and major bleeding events.

Outcome of catheter ablation for paroxysmal atrial fibrillation in patients with stable coronary artery disease.

BACKGROUND: Atrial fibrillation (AF) and stable coronary artery disease (SCAD) frequently coexist. This study aimed to assess the long-term outcome of catheter ablation in patients with paroxysmal AF and SCAD. METHODS: In total, 12,104 patients with paroxysmal AF underwent catheter ablation in the Chinese Atrial Fibrillation Registry between 2011 and 2019 were screened. A total of 441 patients with SCAD were matched with patients without SCAD in a 1:4 ratio. The primary endpoint was AF recurrence after single ablation. The composite secondary endpoints were thromboembolism, coronary events, major bleeding, all-cause death. RESULTS: Over a mean follow-up of 46.0 ± 18.9 months, the recurrence rate in patients with SCAD was significantly higher after a single ablation (49.0% vs. 41.9%, p = .03). The very late recurrence rate of AF in the SCAD group was also significantly higher than that in the control group (38.9% vs. 31.2%;p = .04). In multivariate analysis, adjusted with the female, smoking, duration of AF, previous thromboembolism, COPD, and statins, SCAD was independently associated with AF recurrence (adjusted HR, 1.19 [1.02-1.40], p = .03). The composite secondary endpoints were significantly higher in the SCAD group (12.70% vs. 8.54%, p = .02), mainly due to thromboembolism events (8.16% vs. 4.41%, p < .01). CONCLUSIONS: SCAD significantly increased the risk of recurrence after catheter ablation of paroxysmal AF. The incidence of thromboembolic events after catheter ablation of paroxysmal AF in the patients with SCAD was significantly higher than that in those without SCAD.

Lambl's excrescence and the safety of radiofrequency ablation for atrial fibrillation.

BACKGROUND: Lambl's excrescences (LEs) are excrescences with an extremely low incidence, mainly ultrasound diagnosed. Increasingly, LEs are detected by transesophageal echocardiography before catheter ablation, which raises safety concerns on whether LEs were associated with an embolism event during or after ablation, but clinical data are still lacking. METHODS AND RESULTS: We consecutively recruited 8081 patients with atrial fibrillation who underwent radiofrequency catheter ablation in Beijing Anzhen Hospital from Jan 1, 2017 to Dec 31, 2019. Total 21 patients (0.3%) were diagnosed as LEs with an average age of 70.8 ± 8.9 years, and 38.1% were male. Persistent atrial fibrillation (PeAF) and paroxysmal atrial fibrillation (PAF) accounted for 57.1% (12 cases) and 42.9% (nine cases), respectively. LEs were mostly frequently observed on the aortic valve (18 cases, 75%) and mitral valve (six cases, 25%). Precisely, the noncoronary cusp is ranked first in terms of the LEs presence (seven cases, 29.2%), followed by the right coronary cusp (six cases, 25.0%), the left coronary cusp (five cases, 20.8%), the anterior mitral valve (four cases, 16.7%), and the posterior mitral valve (two cases, 8.3%). During the ablation for LEs patients, the average procedure time was 96.0 ± 22.4 min; the average fluoroscopy time was 4.2 ± 0.8 min; the average total ablation time was 20.6 ± 5.6 min; and the mean hospital stay was 3.3 ± 0.6 days. No patients suffered from serious complications during the procedure. Furthermore, no cardiovascular event was observed during a follow-up of 19.1 ± 11.8 months. CONCLUSIONS: There was no clear association between LEs with intraoperative embolism events or cardiovascular events during the follow-up period.

The Impact of Corporate Capital Structure on Financial Performance Based on Convolutional Neural Network.

Capital structure is an important indicator to measure the source, composition, and proportion of a company's equity and debit capital. It is not only related to the internal operating environment of listed companies but also related to the rights and obligations of shareholders and is closely related to the company's future development direction, decision-making bodies, and changes in governance structure. This study aims to study the impact of corporate capital structure on financial performance based on convolutional neural network. Based on the relevant theories of capital structure, by constructing a convolutional neural network model, taking a listed company as the research object, this study analyzes the company's capital structure, liabilities, and other financial conditions. Finally, it is concluded that short-term liabilities can meet the company's sustainable development and enhance the competitiveness of the industry, thereby increasing the company's operating income. However, a poor capital structure can negatively impact a company's finances. By improving the corporate governance structure of listed companies, strengthening the adjustment of the financing structure of listed companies, and strengthening the management of listed company's operating risks, the company's capital structure can be improved so that the company's financial situation can be sustainable and healthy.

Effects of intensive blood pressure control on cardiovascular and cognitive outcomes in patients with atrial fibrillation: insights from the SPRINT trial.

AIMS: Patients with atrial fibrillation (AF) have an increased risk of cardiovascular events and dementia, even if anticoagulated. Hypertension is highly prevalent in AF population; however, the optimal blood pressure (BP) target for AF patients remains unknown. METHODS AND RESULTS: We conducted subgroup analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) to examine whether AF modified the treatment effects of intensive BP control on cardiovascular and cognitive outcomes using Cox proportional hazards regression and likelihood ratio tests. Among 9361 randomized participants, 778 (8.3%) had baseline AF, and 695 (89.3%) completed at least one follow-up cognitive assessment. Intensive BP control reduced the similar relative risk of cardiovascular events irrespective of the presence of AF, with all interaction P-values > 0.05. Patients with AF experienced a greater absolute risk reduction in the composite primary cardiovascular outcome (12.3 vs. 5.6 events per 1000 person-years) with intensive treatment, compared with those without AF. However, intensive BP control increased the risk of probable dementia in patients with AF [hazard ratio (HR), 2.22; 95% confidence interval (CI), 1.03-4.80], while reducing the dementia risk in patients without AF (HR, 0.75; 95% CI, 0.60-0.95; P = 0.009 for interaction). There were no significant interactions between the presence of AF and intensive BP treatment for mild cognitive impairment. CONCLUSION: Patients with AF experienced greater absolute cardiovascular benefits with intensive BP treatment, but may need to be cautious of an increased risk of dementia. This post hoc analysis should be considered as hypothesis generating and merit further study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

DDIT3/CHOP mediates the inhibitory effect of ER stress on chondrocyte differentiation by AMPKα-SIRT1 pathway.

Endoplasmic reticulum (ER) stress is an evolutionarily conserved cellular stress response related to multiple diseases, including temporomandibular joint (TMJ) cartilage-related diseases. Recent studies have indicated that DDIT3/CHOP (a downstream transcription factor of ER stress) is an important effector in mediating ER stress to inhibit chondrogenesis. However, the underlying mechanism by which DDIT3 regulates chondrogenesis remains unclear. In this study, tunicamycin (an ER stress agonist)-induced ER stress inhibited chondrocyte differentiation and matrix synthesis in vitro and led to an osteoarthritis-like phenotype in mouse TMJ cartilage. Meanwhile, DDIT3 expression in chondrocytes was robustly upregulated. Loss-of-function experiments validated the inhibiting effect of DDIT3 on chondrocyte differentiation and matrix synthesis. Mechanistically, the inhibiting effect was attributed to the direct and indirect regulatory effect of DDIT3 on SIRT1 (sirtuin1, silent mating type information regulation protein type 1, a member of NAD+ dependent class III histone deacetylases). On one hand, DDIT3 directly promoted the transcription of SIRT1. On the other hand, DDIT3 indirectly increased the expression of SIRT1 by promoting AMPKα phosphorylation and activation. Furthermore, activation of AMPKα or SIRT1 with the corresponding agonist AICAR or resveratrol in the DDIT3-knockdown cells partially restored the inhibiting effect of DDIT3 on chondrocyte differentiation and matrix synthesis. Collectively, these novel findings indicate that DDIT3 regulates the inhibitory effect of ER stress on chondrocyte differentiation and matrix synthesis partially via the AMPKα-SIRT1 pathway. A thorough understanding of ER stress in regulating chondrocyte homeostasis and its role in the onset of osteoarthritis may be promising to develop therapeutic targets and prevent condyle cartilage destruction.

Identification of hub genes related to immune cell infiltration in periodontitis using integrated bioinformatic analysis.

BACKGROUND AND OBJECTIVE: Periodontitis is an inflammatory disease of the periodontium. However, the hub genes in periodontitis and their correlation with immune cells are not clear. This study aimed to identify hub genes and immune infiltration properties in periodontitis and to explore the correlation between hub genes and immune cells. MATERIAL AND METHODS: Differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed both on GSE10334 and GSE173078 datasets. Hub genes were identified via WGCNA and DEGs. The proportions of infiltrating immune cells were calculated by CIBERSORT algorithm, and single-cell RNA-sequencing dataset GSE164241 was used to explore cell-type-specific expression profiles of hub genes. RESULTS: Eight hub genes (DERL3, FKBP11, LAX1, CD27, SPAG4, ST6GAL1, MZB1, and SEL1L3) were selected via WGCNA and DEGs by combining GSE10334 and GSE173078 datasets. CIBERSORT analysis showed a significant difference in the proportion of B cells, dendritic cells resting, and neutrophils in the gingival tissues between healthy and periodontitis patients, and expressions of these genes were highly correlated with the infiltration of B cells in periodontitis. Furthermore, real-time quantitative PCR results further confirmed the overexpression of hub genes. Analysis of GSE164241dataset further identified that most of hub genes were mainly expressed in B cells. CONCLUSIONS: By integrating WGCNA, DEGs, and CIBERSORT analysis, eight genes were identified to be the hub genes of periodontitis and most of them were mainly expressed in B cells encouraging further researches on B cells in periodontitis pathogenesis.

Transseptal puncture in patients with septal occluder devices during catheter ablation of atrial fibrillation.

BACKGROUND: An atrial septal occluder (ASO) represents a major obstacle to the widespread adoption of atrial fibrillation (AF) catheter ablation in patients with prior atrial septal defect (ASD) closure. AIMS: The aim of this study was to describe the 'sequential technique' of transseptal puncture (TSP) in AF patients with ASO. METHODS: Sixty-four drug-refractory AF patients with ASO who underwent catheter ablation in our centre from September 2007 to March 2020 were enrolled. RESULTS: Puncture through the native septum was achieved in 29 patients (Group A) and through the device in 35 patients (Group B). The mean diameter of the occluder was significantly larger in Group B than in Group A (31.6±4.6 mm vs 22.8±3.5 mm, p<0.001). The mean time of TSP (24.9±8.8 vs 5.8±2.1 min, p<0.001), total fluoroscopy time (23.7±10.9 vs 7.5±4.4 min, p<0.001), and total procedure time (172.7±58.3 vs 123.4±43.8 min, p=0.001) of Group B were significantly longer than those of Group A. In Group B, the external sheath crossed the device by reshaping the needle and adjusting the puncture angle and position in 23 patients (Group B1), while the external sheath crossed the device with the assistance of balloon dilation in 12 patients (Group B2). No patient had thrombus, periprocedural interatrial shunt or procedural complications. CONCLUSIONS: TSP and AF ablation in patients with ASO are feasible and safe. The 'sequential technique' could be safely used in patients with ASO.