α-Synuclein pathology from the body to the brain:so many seeds so close to the central soil

α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.

Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation

BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin resistance.This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this study.The participants were grouped based on cumulative TyG index values tertiles within 3 months after ablation.Cox regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF recurrence.The predictive value of all risk factors was assessed by receiver operating curve analysis.RESULTS There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values tertiles.After adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index group.The restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index values.When considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after RFCA.Monitoring longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation

Atrial fibrillation(AF)is the most common cardiac arrhythmia.Many medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for AF.Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production.Significant changes occur in myocardial metabolism in AF.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and obesity.GLP-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial function.This article reviews the changes in metabolic characteristics in cardiomyocytes in AF.Although the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.

Research Progress of Atrial Fibrillation Detection Technology

Atrial fibrillation (AF) is the most common chronic arrhythmia in clinical practice, which can cause high disability and mortality with the progress of the disease. Many studies at home and abroad have shown that the incidence of atrial fibrillation gradually increases with age. Clinically, the onset of most AF patients is insidious, which is difficult to capture by routine electrocardiogram, and there is some difficulty in the diagnosis. In order to make the early diagnosis of atrial fibrillation more efficient and accurate, this paper reviews the current status and research progress of detection technology for atrial fibrillation at home and abroad, in order to provide a scientific basis for the early diagnosis of atrial fibrillation.

Global epidemiology of mental disorder in atrial fibrillation between 1998-2021:A systematic review and meta-analysis

BACKGROUND As the burden of mental disorders among patients with atrial fibrillation(AF)increases,researchers are beginning to pay close attention to the risk and prevalence of these comorbidities.Although studies have independently analyzed the risk of comorbidity with depression and anxiety in patients with AF,no study has systematically focused on the global epidemiology of these two mental disorders.AIM To explore the prevalence of depression and anxiety in patients with AF.METHODS Five databases were searched from their date of establishment until January 2023.Observational studies reporting the comorbidity of AF with depression and anxiety,were included in this study.Basic information,such as the first author/publication year,study year,study type,and prevalence of depression and anxiety,were extracted.STATA SE 15.1 was used to analyze the data.Subgroup,meta-regression,and sensitivity analyses were performed to estimate study heterogeneity.RESULTS After a thorough search,26 studies were identified and included in this metaanalysis.The prevalence rates of depression and anxiety in adults with AF were 24.3%and 14.5%,respectively.Among adult males with AF,the prevalence was 11.7%and 8.7%,respectively,whereas in females it was 19.8%and 10.1%,respectively.In older adults with AF,the prevalence rates of depression and anxiety were 40.3%and 33.6%,respectively.The highest regional prevalence of depression and anxiety was observed in European(30.2%)and North American(19.8%)patients with AF.CONCLUSION In this study,we found that the prevalence of depression and anxiety among patients with AF varies with sex,region,and evaluation scales,suggesting the need for psychological interventions for patients with AF in clinical practice.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy:A case report

BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow for significant improvements in both cardiac function and structure;however,this disease has been infrequently documented.In this case,we conducted a longitudinal followup of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7.Since she had no obvious symptoms,she did not receive any treatment to improve her bradycardia during the 42-year follow-up,except for the implantation of a temporary pacemaker during labor induction surgery.As time progressed,the patient's heart gradually expanded due to her low ventricular rate,and she was diagnosed with BIC.In 2014,the patient developed atrial fibrillation,her ventricular rate gradually increased,and her heart shape gradually returned to normal.This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years,introduces another possible outcome of BIC,and emphasizes the importance of early intervention in treating BIC.CONCLUSION BIC can induce atrial fibrillation,causing an increased ventricular rate and leading to positive cardiac remodeling.

Deep Learning-Based ECG Classification for Arterial Fibrillation Detection

The application of deep learning techniques in the medical field,specifically for Atrial Fibrillation(AFib)detection through Electrocardiogram(ECG)signals,has witnessed significant interest.Accurate and timely diagnosis increases the patient’s chances of recovery.However,issues like overfitting and inconsistent accuracy across datasets remain challenges.In a quest to address these challenges,a study presents two prominent deep learning architectures,ResNet-50 and DenseNet-121,to evaluate their effectiveness in AFib detection.The aim was to create a robust detection mechanism that consistently performs well.Metrics such as loss,accuracy,precision,sensitivity,and Area Under the Curve(AUC)were utilized for evaluation.The findings revealed that ResNet-50 surpassed DenseNet-121 in all evaluated categories.It demonstrated lower loss rate 0.0315 and 0.0305 superior accuracy of 98.77%and 98.88%,precision of 98.78%and 98.89%and sensitivity of 98.76%and 98.86%for training and validation,hinting at its advanced capability for AFib detection.These insights offer a substantial contribution to the existing literature on deep learning applications for AFib detection from ECG signals.The comparative performance data assists future researchers in selecting suitable deep-learning architectures for AFib detection.Moreover,the outcomes of this study are anticipated to stimulate the development of more advanced and efficient ECG-based AFib detection methodologies,for more accurate and early detection of AFib,thereby fostering improved patient care and outcomes.

Ibrutinib and atrial fibrillation:An in-depth review of clinical implications and management strategies

Ibrutinib,a targeted therapy for B-cell malignancies,has shown remarkable efficacy in treating various hematologic cancers.However,its clinical use has raised concerns regarding cardiovascular complications,notably atrial fibrillation(AF).This comprehensive review critically evaluates the association between ibrutinib and AF by examining incidence,risk factors,mechanistic links,and management strategies.Through an extensive analysis of original research articles,this review elucidates the complex interplay between ibrutinib’s therapeutic benefits and cardiovascular risks.Moreover,it highlights the need for personalized treatment approaches,vigilant monitoring,and interdisciplinary collaboration to optimize patient outcomes and safety in the context of ibrutinib therapy.The review provides a valuable resource for healthcare professionals aiming to navigate the intricacies of ibrutinib’s therapeutic landscape while prioritizing patient well-being.

Severe hypoxemia after radiofrequency ablation for atrial fibrillation in palliatively repaired tetralogy of Fallot: A case report

BACKGROUND Patients with tetralogy of Fallot(TOF)often have arrhythmias,commonly being atrial fibrillation(AF).Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia,but the risk of complications may increase in patients with conditions such as TOF.CASE SUMMARY We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt.The patient subsequently underwent atrial septal occlusion and eventually recovered.CONCLUSION Radiofrequency ablation may cause iatrogenic atrial septal injury;thus possible complications should be predicted in order to ensure successful treatment and patient safety.

Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Management of cerebral amyloid angiopathy and atrial fibrillation:We are still far from precision medicine

The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.

Construction of A Prediction Model for Atrial Fibrillation in Patients with Dilated Cardiomyopathy and Heart Failure

Dilated cardiomyopathy(DCM)is a common myocardial disease characterized by enlargement of the heart cavity and decreased systolic function,often leading to heart failure(HF)and arrhythmia.The occurrence of atrial fibrillation(AF)is closely related to the progression and prognosis of the disease.In recent years,with the advancement of medical imaging and biomarkers,models for predicting the occurrence of AF in DCM patients have gradually become a research hotspot.This article aims to review the current situation of AF in DCM patients and explore the importance and possible methods of constructing predictive models to provide reference for clinical prevention and treatment.We comprehensively analyzed the risk factors for AF in DCM patients from epidemiological data,pathophysiological mechanisms,clinical and laboratory indicators,electrocardiogram and imaging parameters,and biomarkers,and evaluated the effectiveness of existing predictive models.Through analysis of existing literature and research,this article proposes a predictive model that integrates multiple parameters to improve the accuracy of predicting AF in DCM patients and provide a scientific basis for personalized treatment.

Study of alpha-synuclein fibrillation: state of the art and expectations

Since the discovery of the presence of fibrillary forms ofα-synuclein(α-syn)in Lewy bodies(LB)and Lewy neurites in the brain of patients affected by Parkinson’s disease(PD)and dementia with LB,great effort has been dedicated to study the features ofα-syn fibrillation.In parallel,the pathological relevance of the different toxic forms ofα-syn has been also matter of investigation.In the last twenty years,scientists have been able to single out thatα-syn fibrillation initiates pathological mechanisms that by contributing to or triggering neurodegeneration/neuroinflammation,may lead to PD pathogenesis.This notwithstanding,we still ignore the reasons whyα-syn shifts from its natively unfolded conformation to toxic oligomeric and fibrillary forms.The chameleonic nature of monomericα-syn,and the extremely polymorphic characteristics of aggregated strains,renders it difficult to picture the real nature ofα-syn fibrils,their exact composition and formation dynamics.Recently,sophisticated biophysical methods and microscopy techniques have been exploited to studyα-syn fibrillation.Here,we provide an overview of the most relevant advancement in our understanding ofα-syn fibrils formation and conformation.

Development and Validation of a Postoperative Prognostic Nomogram to Predict Recurrence in Patients with Persistent Atrial Fibrillation:A Retrospective Cohort Study

Background:Patients with persistent atrial fibrillation(PsAF)have a high risk of recurrence after catheter radiofre-quency ablation.Nevertheless,no effective prognostic tools have been developed to identify these high-risk patients to date.This study sought to develop and validate a simple linear predictive model for predicting postoperative recurrence in patients with PsAF.Methods:From June 2013 to June 2021,patients with PsAF admitted to our hospital were enrolled in this single-center,retrospective,observational study.The characteristics substantially associated with recurrence in patients with PsAF were screened through univariate and multivariate logistic regression analysis.The receiver operating charac-teristic curve was used to assess the predictive significance of the nomogram model after nomogram development.Furthermore,to assess the clinical value of the nomogram,we performed calibration curve and decision curve analyses.Results:A total of 209 patients were included in the study,42(20.10%)of whom were monitored up to 1 year for recurrent AF.The duration of AF episodes,left atrial diameter,BMI,CKMB,and alcohol consumption were found to be independent risk factors(P<0.05)and were integrated into the nomogram model development.The area under the curve was 0.895,the sensitivity was 93.3%,and the specificity was 71.4%,thus indicating the model’s excellent predic-tive ability.The C-index of the predictive nomogram model was 0.906.Calibration curve and decision curve analyses further revealed that the model had robust prediction and strong discrimination ability.Conclusion:This simple,practical,and innovative nomogram can help clinicians in evaluation of the risk of PsAF recurrence after catheter ablation,thus facilitating preoperative evaluation,postoperative monitoring and ultimately the construction of more personalized therapeutic protocols.

Atrial fibrillation and coronary artery disease:An integrative review focusing on therapeutic implications of this relationship

The incidence of both atrial fibrillation(AF)and coronary artery disease(CAD)increases with advancing age.They share common risk factors and very often coexist.Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level.In this review,we delineated this complex relationship,identified a common theme between the two,and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management.Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography.Further,the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship.CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity.AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system.In a nutshell,the two form a vicious cycle wherein one disease promotes the other.Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism.Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients.Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases.The relationship between AF and CAD is complex and much more than mere coincidence.The two diseases share common risk factor and pathophysiology.Hence,it is impractical to treat them in isolation.Accordingly,we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.

Mendelian randomization provides evidence for a causal effect of serum insulin-like growth factor family concentration on risk of atrial fibrillation

BACKGROUND Atrial fibrillation(AF)is one of the most common persistent arrhythmias among adult cardiovascular diseases.It is important to identify potential risk factors for AF.Members of the insulin-like growth factor(IGF)family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.assess genetic relationships between IGF family members and AF.METHODS MR was performed based on genome-wide association study(GWAS)datasets,and concentration levels of 14 IGF family members were retrieved.An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations.A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects.Two-sample MR packages were used to perform MR analysis in R.MR-Egger,weighted median(WM),and inverse va-riance weighted(IVW)methods were used.RESULTS Core Tip:Due to the high prevalence of atrial fibrillation(AF),and adverse outcomes related to it,it is important to identify risk factors associated with development of the condition.Insulin-like growth factor(IGF)family members exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases,and previous population-based studies indicate associations between IGF family members and AF.However,the causal effects of IGF family members in AF have not been evaluated.The results of the current study provide novel insights on the pathogenesis of AF,and implic-ations of serum IGF family member concentrations when assessing the risk of AF.The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF.Further observational and experimental studies are critically needed.

Three-year outcomes of patients with non-valvular atrial fibrillation: the COOL-AF registry

BACKGROUND Clinical outcomes of patients with non-valvular atrial fibrillation(AF)in Asian populations may be different from non-Asians.In this study,we aimed to determine the incidence of ischemic stroke/systemic embolism(SSE),major bleeding,and death,and the predictors for clinical outcomes in a contemporary Asian cohort of newly diagnosed AF patients.METHODS This is a prospective multicenter nationwide registry of patients with AF from 27 hospitals in Thailand.Baseline data and follow-up data were collected every 6 months until 3 years.Data collections included demographic,medical history,laboratory,and medication details.Clinical outcomes were SSE,major bleeding,and all-cause mortality.Incidence rates for each clinical outcome were calculated and presented as rate per 100 person-years.Univariate and multivariate analysis was performed to determine the independent predictors for clinical outcomes.RESULTS There was a total of 3405 patients:mean age was 67.8±11.3 years,1981(58.2%)were male.During 30.8±9.7 months follow-up,there was a total of 132 SSE(3.9%),191 major bleeding(5.6%),and 357 all-cause deaths(10.5%).The incidence rates of SSE,major bleeding,and death were 1.56(1.30-1.84),2.26(1.96-2.61),and 4.17(3.33-4.25),per 100 person-years respectively.Independent predictors for clinical outcomes were age,type of AF,and the presence of comorbid conditions.CONCLUSION The incidence rate of SSE,major bleeding,and death remains high reflecting the unmet needs in AF management。

Predictive value of bleeding risk scores in elderly patients with atrial fibrillation and oral anticoagulation

BACKGROUND The predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well known.The goal of this study was to evaluate the predictive value of HASBLED,ORBIT and ATRIA for major bleeding(MB)and intracranial hemorrhage(ICH)in patients≥75 years with atrial fibrillation and oral anticoagulation(OAC).METHODS A retrospective unicenter study including patients≥75 years with atrial fibrillation(AF)and OAC.A total of 7613 patients≥75 years with AF and OAC included between 2014 and 2018(registry:NCT04364516).We analyzed the discriminative value of HASBLED,ATRIA and ORBIT scores for bleeding endpoints(major bleeding as primary endpoint and intracerebral hemorrhage as secondary).Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major bleeding.Model discrimination was assessed using Harrell’s C-statistic.Calibration was assessed with goodness-of-fit test proposed by Gronnesby and Borgan.RESULTS During a mean follow up of 4.0 years(IQR:2.4–5.7 years),729 patients developed MB(2.61 per 100 patients/year)and 243 patients developed ICH(0.85 per 100 patients/year).Three scores showed a low discrimination for major bleeding,being ORBIT the best(HASBLED C statistic=0.557;ATRIA C statistic=0.568;ORBIT C statistic=0.595)and also a low discrimination for ICH(HASBLED C statistic=0.509;ATRIA C statistic=0.522;ORBIT C statistic=0.526).Among the variables that are part of the scores and other baseline characteristics,after multivariable adjustment only sex(male),dementia,prior admission for bleeding,anemia and liver disease were found as a predictors of MB.CONCLUSIONS In older patients under oral anticoagulation with atrial fibrillation,the risk scores HASBLED,ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial hemorrhage.Therefore,other better alternatives should be evaluated for this purpose.

Circulating circRNA expression profile and its potential role in late recurrence of paroxysmal atrial fibrillation post catheter ablation

BACKGROUND Catheter-based pulmonary vein isolation(PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation(PAF). Nevertheless, late recurrences of atrial fibrillation(LRAF) occurring during 3 to 12months are common, and the underlying mechanisms remain elusive. Circular RNAs(circ RNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear.METHODS In the present study, the expression profile of circulating circ RNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction(q RT-PCR). Bioinformatics analyses, including Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis, and circ RNA/mi RNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed(DE) circ RNAs.RESULTS A total of 12,834 circ RNAs, comprising 5,491 down-regulated and 7,343 up-regulated circ RNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity,cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circ RNAs is endocytosis. In the circ RNA/micro RNAs interaction network, four up-regulated circ RNAs(hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circ RNA(hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF.CONCLUSIONS This investigation discovered the expression pattern of circulating circ RNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI.