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.

Atrial fibrillation and prediabetes:A liaison that merits attention!

Atrial fibrillation(AF)and prediabetes share common pathophysiological mechanisms with endothelial dysfunction and inflammation playing a key role.The resultant vicious cycle which sets in culminates in a higher atherogenicity and thermogenicity of the vascular system resulting in increased major adverse cardiac or cerebrovascular event(MACCE)events.However,the same has not convincingly been verified in real-world settings.In the recent retrospective study by Desai et al amongst AF patients being admitted to hospitals following MACCE,prediabetes emerged as an independent risk factor for MACCE after adjusting for all confounding variables.However,certain questions like the role of metformin,quantifying the risk for MACCE amongst prediabetes compared to diabetes,the positive impact of reversion to normoglycemia remain unanswered.We provide our insights and give future directions for dedicated research in this area to clarify the exact relationship between the two.

The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives

Regulation of gut microbiota and its impact on human health is the theme of intensive research.The incidence and prevalence of atrial fibrillation(AF)are continuously escalating as the global population ages and chronic disease survival rates increase;however,the mechanisms are not entirely clarified.It is gaining awareness that alterations in the assembly,structure,and dynamics of gut microbiota are intimately engaged in the AF progression.Owing to advancements in next-generation sequencing technologies and computational strategies,researchers can explore novel linkages with the genomes,transcriptomes,proteomes,and metabolomes through parallel meta-omics approaches,rendering a panoramic view of the culture-independent microbial investigation.In this review,we summarized the evidence for a bidirectional correlation between AF and the gut microbiome.Furthermore,we proposed the concept of“gut-immune-heart”axis and addressed the direct and indirect causal roots between the gut microbiome and AF.The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions,which shed light on a definite direction for future experiments.

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.

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.

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.

Atrial fibrillation and prediabetes:Interplay between left atrium and systemic diseases

Atrial fibrillation(AF)is associated with multiple other comorbidities,i.e.multimorbidity.Prediabetes is one of the multiple comorbidities observed in patients with AF,whereby these two disease entities share the same pathophysiological mechanisms,namely oxidative stress and inflammation.Although prediabetes is reported to have a negative impact on major adverse cardiac or cerebrovascular events in hospitalized AF patients,information about the interactions between prediabetes and AF remains inconsistent.A more in-depth exploration of pathophysiology and more comprehensive prospective clinical studies of AF and diabetes would provide a thorough understanding of the timing of events and further treatment strategies.Deeper investigations are needed to clarify the interactions and causal relationships between AF and prediabetes.

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.

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.

Relationship of inflammatory indices with left atrial appendage thrombus or spontaneous echo contrast in patients with atrial fibrillation

BACKGROUND Inflammatory indices derived from complete blood tests have been reported to be associated with poor outcomes in patients with atrial fibrillation(AF).The data about the relationship between inflammatory indices and left atrial appendage thrombus(LAAT)or dense spontaneous echo contrast(SEC)are limited.AIM To explore the value of inflammatory indices for predicting the presence of LAAT or dense SEC in nonvalvular AF patients.METHODS A total of 406 patients with nonvalvular AF who underwent transesophageal echocardiography were included and divided into two groups based on the presence(study group)or absence(control group)of LAAT or dense SEC.Inflammatory indices,including the neutrophil-to-lymphocyte ratio(NLR),platelet–tolymphocyte ratio(PLR),and lymphocyte-to-monocyte ratio(LMR),were calculated from complete blood analysis.The associations of inflammatory indices RESULTS LAAT and dense SEC were detected in 11(2.7%)and 42(10.3%)patients,respectively.The PLR only showed an association with LAAT/dense SEC in the univariate model.Elevated NLR(odds ratio[OR]=1.48,95%confidence interval[CI]:1.11-1.98,P=0.007)and reduced LMR(OR=0.59,95%CI:0.41-0.83,P=0.003)were found to be independent risk factors for the presence of LAAT/dense SEC.The areas under the NLR and LMR curves for predicting LAAT/dense SEC were 0.73(95%CI:0.66-0.80,P<0.001)and 0.73(95%CI:0.65-0.81,P<0.001),respectively,while the cutoff values were 2.8(sensitivity:69.8%;specificity:64.0%)and 2.4(sensitivity:71.7%;specificity:60.6%),respectively.CONCLUSION Increased NLR and decreased LMR may predict LAAT/dense SEC in patients with nonvalvular AF.

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.

Pharmacological Treatment for Atrial Fibrillation—Modalities in Equines and Companion Animals

Cardiac arrhythmias are probably more common in horses than in any other domestic animal species where poor performance and exercise intolerance is the most frequent clinical complaint. Atrial fibrillation is a type of cardiac arrhythmia that appears as a common finding during medical examinations in humans, large breed dogs and horses. Clinical presentations are of a particular value in racehorses in high performing activities. Atrial fibrillation is characterized by an irregular heart rhythm, secondary to a primary disease or without any sign of comorbidity. The generation and maintenance of Atrial Fibrillation requires a substrate. Some breeds have a genetic predisposition to developing Atrial Fibrillation. Most cases of Atrial Fibrillation are of the paroxysmal type and self-regulate within a few hours to days without the need for treatment. The focus of this study is on the arrhythmic agents that are used for the treatment of Atrial Fibrillation, therefore other arrhythmic agents may not be included, or are included to demonstrate their effect on increasing, inhibiting or decreasing efficacy when used together with medications for the treatment of Atrial Fibrillation. The “working horse” for the pharmacological treatment of Atrial Fibrillation is Quinidine.

Association of cannabis use disorder with atrial fibrillation in young men without concomitant tobacco use:Insights from nationwide propensity matched analysis

BACKGROUND Recent data are inconclusive regarding the risk of arrhythmias among young cannabis users.Furthermore,many young adults use both cannabis and tobacco,which could add a residual confounding effect on outcomes.So,we studied young men who have cannabis use disorder(CUD)excluding tobacco use disorder(TUD)to understand their independent association with atrial fibrillation(AF)and related outcomes.AIM To study the association of CUD with AF and related outcomes.METHODS We used weighted discharge records from National Inpatient Sample(2019)to assess the baseline characteristics and mortality rates for AF-related hospitalizations in young(18-44 years)men in 1:1 propensity-matched CUD+vs CUD-cohorts without TUD.RESULTS Propensity matched CUD+and CUD-cohorts consisted of 108495 young men in each arm.Our analysis showed an increased incidence of AF in black population with CUD.In addition,the CUD+cohort had lower rates of hyperlipidemia(6.4%vs 6.9%),hypertension(5.3%vs 6.3%),obesity(9.1%vs 10.9%),alcohol abuse(15.5%vs 16.9%),but had higher rates of anxiety(24.3%vs 18.4%)and chronic obstructive pulmonary disease(COPD)(9.8%vs 9.4%)compared to CUD-cohort.After adjustment with covariates including other substance abuse,a non-significant association was found between CUD+cohort and AF related hospitalizations(odd ratio:1.27,95%confidence interval:0.91-1.78,P=0.15).CONCLUSION Among hospitalized young men,the CUD+cohort had a higher prevalence of anxiety and COPD,and slightly higher proportion of black patients.Although there were higher odds of AF hospitalizations in CUD+cohort without TUD,the association was statistically non-significant.The subgroup analysis showed higher rates of AF in black patients.Large-scale prospective studies are required to evaluate long-term effects of CUD on AF risk and prognosis without TUD and concomitant substance abuse.

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.

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.

New-onset atrial fibrillation among COVID-19 patients: A narrative review

Over the last three years,research has focused on examining cardiac issues arising from coronavirus disease 2019(COVID-19)infection,including the emergence of new-onset atrial fibrillation(NOAF).Still,no clinical study was conducted on the persistence of this arrhythmia after COVID-19 recovery.Our objective was to co-mpose a narrative review that investigates COVID-19-associated NOAF,emphasi-zing the evolving pathophysiological mechanisms akin to those suggested for sustaining AF.Given the distinct strategies involved in the persistence of atrial AF and the crucial burden of persistent AF,we aim to underscore the importance of extended follow-up for COVID-19-associated NOAF.A comprehensive search was conducted for articles published between December 2019 and February 11,2023,focusing on similarities in the pathophysiology of NOAF after COVID-19 and those persisting AF.Also,the latest data on incidence,morbidity-mortality,and management of NOAF in COVID-19 were investigated.Considerable overlaps between the mechanisms of emerging NOAF after COVID-19 infection and persistent AF were observed,mostly involving reactive oxygen pathways.With potential atrial remodeling associated with NOAF in COVID-19 patients,this group of patients might benefit from long-term follow-up and different management.Future cohort studies could help determine long-term outcomes of NOAF after COVID-19.

Using Magnesium Sulfate to Prevent Atrial Fibrillation after Coronary Artery Bypass Grafting Surgery: A Single Centre Experience in Bangladesh

Background: Atrial fibrillation commonly occurs following cardiac surgery, particularly after coronary artery bypass grafting. Magnesium, known for its stabilizing effect on cell membranes, has shown promise in preventing postoperative atrial fibrillation. This study aimed to assess the impact of intravenous magnesium infusion in preventing atrial fibrillation after off-pump coronary artery bypass grafting, where maintaining stable cell membranes is crucial in averting this complication. Methods: A cross-sectional study was conducted at the Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, from March 2020 to February 2022. Sixty-six patients who underwent off-pump coronary artery bypass grafting were enrolled and divided into two groups. Group A (n = 33) received intravenous magnesium sulfate (10 mmol/2.47gm) for three days after surgery, while Group B (n = 33) did not receive magnesium sulfate. Postoperative atrial fibrillation occurrence in the Intensive Care Unit (ICU) within three days after surgery was evaluated using convenient sampling. Statistical analysis was performed with SPSS version 26.0, utilizing independent Student’s t-test for continuous data and Chi-square and Fisher’s exact test for categorical data. A p-value of ≤0.05 was considered statistically significant. Results: No significant differences in age or gender were observed between the two groups. Group B exhibited significantly lower magnesium levels than Group A on the 0th, 1st, 2nd, and 3rd days post-surgery. Additionally, Group B experienced a higher incidence of postoperative atrial fibrillation, longer ICU stays, and two mortalities. The study did not detect any adverse effects associated with magnesium infusion. Conclusion: It has been demonstrated that administering magnesium intravenously after off-pump coronary artery bypass grafting can lower the chances of developing atrial fibrillation. This demonstrates the potential advantages of using magnesium as a preventative measure for postoperative atrial fibrillation in such cases.

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.

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.

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.