Independent Risk Factor For Atrial Fibrillation Research Articles

Association of sarcopenia with the long-term risk of atrial fibrillation: A prospective cohort study.

The relationship between sarcopenia and the long-term risk of atrial fibrillation (AF) remains unclear. This study recruited a large prospective Caucasian cohort from the UK Biobank. Participants were assessed at baseline with handgrip strength and muscle mass and were categorized into groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia. Kaplan-Meier method and Cox proportional hazards model were used to explore the association between sarcopenia and the incidence of AF. The genetic predisposition of AF was assessed by polygenic risk score. Sensitivity analyses were performed to validate the results. A total of 384,433 participants with a median age of 58 years and 54.3% women were enrolled in this study. There were 24,007 cases of new-onset AF over a median follow-up of 12.56 years. The groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia accounted for 22,290 (6.1%), 1665 (9.2%), and 52 (11.9%) cases, respectively. Compared with the non-sarcopenia group, participants with probable sarcopenia or confirmed sarcopenia had an 8% (95% CI, 1.03-1.14) or 61% (95% CI, 1.23-2.12) higher risk of AF incidence. The findings remained robust in multiple sensitivity analyses, such as subgroup analysis and further adjustment of genetic predisposition. Notably, the association between sarcopenia and a high AF risk was more pronounced in younger participants, women, and those with valvular heart disease. In conclusion, sarcopenia was associated with a high long-term risk of AF in Caucasians, supporting sarcopenia as a new independent risk factor of AF.

Predictors of atrial fibrillation after embolic stroke of undetermined source in patients with implantable loop recorders.

In patients with embolic stroke of undetermined source (ESUS), underlying subclinical atrial fibrillation (AF) is often suspected. Previous studies identifying predictors of AF have been limited in their ability to diagnose episodes of AF. Implantable loop recorders enable prolonged, continuous, and therefore more reliable detection of AF. The aim of this study was to identify clinical and ECG parameters as predictors of AF in ESUS patients with implantable loop recorders. 101 ESUS patients who received an implantable loop recorder between 2012 and 2020 were included in this study. Patients were followed up regularly on a three-monthly outpatient interval. During a mean follow-up of 647 ± 385days, AF was detected in 26 patients (26%). Independent risk factors of AF were age ≥ 60years (HR 2.753, CI 1.129-6.713, p = 0.026), P-wave amplitude in lead II ≤ 0.075mV (HR 3.751, CI 1.606-8.761, p = 0.002), and P-wave duration ≥ 125ms (HR 4.299, CI 1.844-10.021, p < 0.001). In patients without risk factors, the risk of developing AF was 16%. In the presence of one risk factor, the probability increased only slightly to 18%. With two or three risk factors, the risk of AF increased to 70%. AF was detected in about one in four patients after ESUS in this study. A comprehensive evaluation involving multiple parameters and the existence of multiple risk factors yields the highest predictive accuracy for detecting AF in patients with ESUS.

Age-Dependent Detection of Atrial Fibrillation with Implantable Cardiac Monitors in Patients with Cryptogenic Stroke.

Background Continuous monitoring using implantable cardiac monitors (ICMs) results in atrial fibrillation (AF) detection rates of up to 30% in patients with cryptogenic stroke (CS). Although higher age is an independent risk factor for AF, there are no age-specific recommendations for the implantation of ICM. Objective The aim of this study was to analyze age-related AF rates in patients with CS and continuous rhythm monitoring, to determine the rates of oral anticoagulation (OAC) and recurrent cerebrovascular events (stroke or transient ischemic attack) in patients with ICM-detected AF, and to describe the temporal relationship of AF detection and recurrent cerebrovascular events. Methods In this observational study, patients with CS provided with ICMs were systematically followed. All patients underwent 72-hour electrocardiography monitoring, transcranial Doppler ultrasound, and transthoracic echocardiography prior to ICM insertion. Follow-up included a regular outpatient presentation every 3 months with medical history, physical examination, and interrogation of the ICM. Results One-hundred eighty-six patients (mean age: 65 ± 12 years, 54% female) were included in this analysis. AF was detected in 6, 27, 56, and 65% ( p < 0.001) of patients aged less than 60, 60 to 69, 70 to 79, and more than or equal to 80 years, respectively. All patients with AF under 60 years had an impaired left ventricular systolic function. OAC was initiated in 85% of the patients with AF. Recurrent cerebrovascular events occurred in 34 patients of whom 14 had a diagnosis of AF. In nine patients, AF was diagnosed before the occurrence of a recurrent cerebrovascular event. Conclusion AF prevalence increased with age and was absent in CS patients younger than 60 years and with preserved left ventricular ejection fraction. The temporal relationship of AF and recurrent cerebrovascular events was weak.

Effect of type 2 diabetes on cardiac arrhythmias in patients with obstructive hypertrophic cardiomyopathy

AimsType 2 diabetes (T2D), a prevalent cardiovascular disease, is linked with cardiac arrhythmias such as atrial fibrillation (AF) and ventricular arrhythmia. This study evaluated T2D's impact on these arrhythmias in patients with obstructive hypertrophic cardiomyopathy (OHCM). Methods and materialsWe retrospectively analyzed the data of 75 patients with OHCM and T2D from two medical centers in China from 2011 to 2020. A propensity score-matched cohort of 150 patients without T2D was also analyzed. ResultsAltogether, 225 patients were included. The prevalence of supraventricular tachycardia (SVT), AF, and non-sustained ventricular tachycardia (NSVT) was higher in patients with HCM and T2D than in those without T2D. Multivariate logistic regression showed T2D as an independent risk factor for SVT (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.01–3.58, P = 0.04), AF (OR = 2.68, 95% CI = 1.27–5.67, P = 0.01), and NSVT (OR = 2.18, 95% CI = 1.04–4.57, P = 0.04). Further analysis identified fasting glucose and glycosylated hemoglobin levels as independent risk factors for AF and NSVT in patients with T2D. ConclusionsT2D independently increases the risk of cardiac arrhythmias (SVT, AF, NSVT) in OHCM patients. Furthermore, fasting glucose and glycosylated hemoglobin levels independently heighten AF and NSVT risk in OHCM patients with T2D.

Predictive nomogram models for atrial fibrillation in COPD patients: A comprehensive analysis of risk factors and prognosis.

The aim of the present study was to identify the independent risk factors and prognostic indicators for atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) and to develop predictive nomogram models. This retrospective study included a total of 286 patients with COPD who were admitted to the Second Affiliated Hospital of Guilin Medical College between January 2020 and May 2022. The average age of the patients was 77.11±8.67 years. Based on the presence or absence of AF, the patients were divided into two groups: The AF group (n=87) and the non-AF group (n=199). Logistic regression analysis was conducted to identify variables with significant differences between the two groups. Nomogram models were constructed to predict the occurrence of AF in COPD patients and to assess prognosis. Survival analysis was performed using the Kaplan-Meier method. The follow-up period for the present study extended until April 31, 2023. Survival time was defined as the duration from the date of the interview to the date the participant succumbed or the end of the follow-up period. In the present study, age, uric acid (UA) and left atrial diameter (LAD) were found to be independent risk factors for the development of AF in patients diagnosed with COPD. The stepwise logistic regression analysis revealed that age had an odds ratio (OR) of 1.072 [95% confidence interval (CI): 1.019-1.128; P=0.007], UA had an OR of 1.004 (95% CI: 1.001-1.008; P=0.010) and LAD had an OR of 1.195 (95% CI: 1.098-1.301; P<0.001). Univariate and multivariate Cox regression analysis revealed that LAD and UA were independent prognostic factors for long-term mortality in COPD patients with AF. LAD had a hazard ratio (HR) of 1.104 (95% CI: 1.046-1.165; P<0.001) and UA had an HR of 1.004 (95% CI: 1.000-1.008; P=0.042). Based on these findings, predictive nomogram models were developed for AF in COPD patients, which demonstrated good discrimination ability with an area under the curve of 0.886. The prognostic nomogram for COPD patients with AF also showed good predictive accuracy with a concordance index of 0.886 (95% CI: 0.842-0.930). These models can provide valuable information for risk assessment and prognosis evaluation in clinical practice. Age, UA and LAD are independent risk factors for AF in COPD patients. The developed nomogram models provide a reliable tool for predicting AF in COPD patients and for prognosis assessment.

Age-dependent detection of Atrial Fibrillation with implantable cardiac monitors in patients with cryptogenic stroke

Abstract Background Prolonged and intensified rhythm monitoring is recommended to detect atrial fibrillation (AF) in patients with cryptogenic stroke (CS). Continuous monitoring using implantable cardiac monitors (ICM) results in AF detection rates of up to 30%. Although higher age has been identified as an independent risk factor for AF in patients post CS, there are no specific recommendations for the implantation of ICM in younger patients. Furthermore, the temporal relationship between AF and recurrent stroke in patients with continuous monitoring is a relevant issue and scarcely investigated. Objectives (1)To analyze age-related AF rates in patients with CS and continuous rhythm monitoring using ICM. (2)To determine the rates of oral anticoagulation and recurrent strokes in patients with ICM-detected AF after CS. (3)To describe the temporal relationship of AF detection and recurrent stroke in these patients. Methods From 02/2014 to 11/2021, patients with CS provided with ICMs were systematically followed. All patients underwent 72-h ECG monitoring, transcranial doppler ultrasound and transthoracic echocardiography according to current guidelines prior to ICM insertion. Follow-up was performed by means of a regular outpatient presentation every three months and included medical history, physical examination, and interrogation of the ICM. AF was defined as any episode of absolute arrhythmia &amp;gt;30 seconds. Results One hundred and eighty-six patients (mean age 65 ± 12 years) were included in this analysis. AF was detected in 62 patients (33 %) during a mean follow-up of 36 ± 23 months. AF was found in 6 % (3/52), 27 % (17/62), 56 % (31/55) and 65 % (11/17) (p &amp;lt; 0.001) in patients aged &amp;lt; 60 years, 60-69 years, 70-79 years and ≥ 80 years, respectively (see Figure 1). All patients with AF under 60 years had an impaired systolic left ventricular function (left ventricular ejection fraction &amp;lt; 50 %). Oral anticoagulation was initiated in 85% of the patients with AF. Recurrent stroke occurred in 34 patients (18.3%) of whom fifteen had a diagnosis of AF. In nine patients, AF was diagnosed before the occurrence of a recurrent stroke. In four patients, AF was diagnosed after recurrent stroke and in one patient, AF and recurrent stroke occurred simultaneously (see Figure 2). Conclusion AF was absent in cryptogenic stroke patients with preserved ejection fraction and younger than 60 years. AF prevalence increased with age. The temporal relationship of AF and recurrent stroke was weak. Further research is needed to better identify stroke patients at risk of AF and recurrent stroke. Figure 1: Time to first detection of Atrial fibrillation in patients aged &amp;lt; 60 years, 60-69 years, 70-79 years and ≥80 years, respectively. Figure 2: Temporal relationship of first detected atrial fibrillation (AF) and recurrent stroke in patients with cryptogenic stroke.Figure 1Figure 2

Abstract 18192: Sleep Apnea and Incident Atrial Fibrillation : Implications for Targeted Screening

Introduction: In younger individuals, the factors contributing to atrial fibrillation (AF) and ischemic stroke are not entirely understood. Despite the frequent coexistence of obstructive sleep apnea (OSA) and AF, current guidelines do not advise routine screening for either condition. Hypothesis: OSA may be an independent predictor of AF in younger adults Methods: We mined electronic health records of patients aged 20-50 Y who have had &gt;=2 visits within Stanford Healthcare System during the period of 2008 to 2022. Our primary endpoint was incident AF. A comprehensive list of risk factors was mined as covariates. Time-varying covariate survival analysis was done to relate the covariates to the primary endpoint. Analysis was performed in R. Results: From a total population of approximately 1.3 million patients aged between 20 and 50 years, we identified 541168 individuals. Among them, 66088 (12.2%) had OSA. During the follow-up, 5060 young adults (67 per 100,000 person-years) developed new AF. In the multivariable adjusted time-varying analysis, apart from previously reported cardiovascular and demographic risk factors, sleep apnea [aHR:1.13 (1.06,1.20)], CKD [aHR:1.91 (1.22,1.44)], cancer [aHR:1.12, (1.04,1.20)], chronic liver disease [aHR:1.13, (1.05,1.21)] were independent risk factors of AF (Fig 1a). Although risk portended by sleep apnea may be slightly lower than some CHADS2VASC factors, sleep apnea is much more prevalent than them, which may support the benefit for screening in this young population (Fig 1b). Conclusions: In a cohort of over half a million adults aged between 20 and 50, sleep apnea significantly and independently predicts incident AF, which may have implications in screening and treatment strategies for younger patients.

Increased Left Atrial Stiffness is Significantly Associated with Paroxysmal Atrial Fibrillation in Diabetic Patients.

Atrial fibrillation (AF) and diabetes mellitus (DM) are common pathogenic diseases. Diabetes is an independent risk factor for AF, and coexisting AF is a risk factor for the diabetic pa-tient's progression. The purpose of this study was to see if two-dimensional-speckle tracking echocardiography (2D-STE) might provide valuable criteria for determining the risk of AF in diabetic patients. This retrospective study compared 30 adult diabetic patients with documented paroxysmal atrial fibrillation (PAF) with 30 age- and sex-matched diabetic patients without PAF. Inclusion criteria were: age ≥18 years, sinus rhythm, diabetes mellitus type 2, and the ability to sign the informed consent. Exclusion criteria included: moderate or severe valvular disease, previous myocardial infarction, left ventricular ejection fraction (LVEF) <50%, congenital heart disease, a history of cardiac surgery, paced atrial or ventricular rhythm, inadequate echocardiography imaging. The medical history, clinical, biochemical data and the results of the transthoracic cardiac ultrasound examination were registered during their evaluation at the outpatients cardiology clinics. The mean age of the patients was 62.5±1.7 years, 60% were men. Diabetic patients who experienced PAF episodes demonstrated significantly impaired left atrial (LA) deformation patterns, with decreased LA strains and increased LA stiffness (p < 0.05). The present study demonstrates that LA strains and LA stiffness are significantly associated with the occurrence of PAF in diabetic patients. As 2D-STE of the LA is more sensitive than routine echocardiographic examination, it should be performed in patients suspected of being suffering from PAF.

Correlation between the triglyceride-glucose index and the onset of atrial fibrillation in patients with non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with atrial fibrillation (AF). Insulin resistance (IR) is the main cause of the high prevalence of AF in NAFLD patients. The triglyceride-glucose index (TyG) is a novel IR-related indicator implicated in the incidence and severity of NAFLD. However, the role of TyG in determining the risk for AF in patients with NAFLD remains unclear.MethodsA retrospective study was conducted on 912 patients diagnosed with NAFLD via ultrasonography. These patients were divided into two groups: (1) NAFLD+ AF and (2) NAFLD+ non-AF. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to assess the correlation between the TyG index and the high risk for AF. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value for the TyG index for AF. Restricted cubic splines (RCS) were used to test the linear correlation between TyG and the risk for AF.ResultsA total of 204 patients with AF and 708 patients without AF were included in this study. The LASSO logistic regression analysis showed that TyG was an independent risk factor for AF (odds ratio [OR] = 4.84, 95% confidence interval [CI] 2.98–7.88, P < 0.001). The RCS showed that the risk for AF increased linearly with TyG over the entire TyG range; this risk was also evident when the patients were analyzed based on sex (P for nonlinear > 0.05). In addition, the correlation between TyG and AF was a consistent finding in subgroup analysis. Furthermore, ROC curve analysis showed that TyG levels combined with traditional risk factors improved the predictive value for atrial fibrillation.ConclusionThe TyG index is useful in assessing the risk for atrial fibrillation in patients with NAFLD. Patients with NAFLD and increased TyG indices have higher risks for atrial fibrillation. Therefore, TyG indices should be assessed when managing patients with NAFLD.

The monocyte-to-high-density lipoprotein ratio is associated with the occurrence of atrial fibrillation among NAFLD patients: A propensity-matched analysis.

Accumulating evidence suggests that patients with nonalcoholic fatty liver disease (NAFLD) have a significantly high risk of incident atrial fibrillation (AF). Systemic inflammation, metabolic disorders and oxidative stress could be the potential mechanisms by which NAFLD drives AF. Monocyte-to- high-density lipoprotein ratio (MHR) has emerged as a novel biomarker of inflammation and oxidative stress that has not been studied in AF with NAFLD patients. We aimed to investigate the relationship between MHR and the risk of AF among NAFLD patients. A retrospective analysis was performed for the clinical data of the patients with NAFLD in the Second Hospital of Shanxi Medical University from January 2019 to October 2022, among whom 204 patients with AF were enrolled as NAFLD+AF group and 613 patients without AF were enrolled as NAFLD control, and 152 patients were selected from each group based on propensity score matching (PSM) at a ratio of 1:1 to balance the covariates between groups. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Logistic regression analysis was performed to identify the independent predictor for occurrence of AF among NAFLD patients. Trend chi-square test to analyze the prevalence of AF among MHR tertiles, and then the correlation between MHR and the risk of AF confirmed by restricted cubic splines (RCS). The receiver operating characteristic (ROC) curve analysis was used to determine the optimum MHR cutoff value to predict AF. Univariate analysis showed that AF patients had higher MHR than non-AF patients (P < 0.001). Meanwhile, compared with pure NAFLD patients, multivariate logistic regression analysis showed that MHR remained to be an independent risk factor for AF after adjusting for confounding risk factors (OR = 10.67, 95% CI 2.17-52.37, P = 0.004). TC、HDL-C were also independent risk factors for AF. Among them, TC and HDL-C are protective factors for AF. The trend chi-square test showed that the risk of AF increased with an increase in MHR (P < 0.05). However, the RCS showed a nonlinear and J-shaped relationship between MHR and the risk of AF (P for non-linearity = 0.023). The occurrence of AF increased with increasing MHR only when MHR > 0.44. The ROC curve showed that MHR combined with traditional risk factors can improve the ability to predict AF. MHR is an independently associated with incident AF in patients with NAFLD and show a certain predictive value.

Risk factors and SCN5A-H558R polymorphism for atrial fibrillation in Tibetans living at different altitudes.

Several studies have found associations of genes with atrial fibrillation (AF), including SCN5A-H558R. However, there are limited data of these associations among populations living at different altitudes. We investigated the relationship between the SCN5A-H558R polymorphism and AF in Tibetans living at different altitudes in Qinghai, China. General clinical and genotype data were obtained from 72 patients with AF and 109 non-AF (NAF) individuals at middle altitudes, and from 102 patients with AF and 143 NAF individuals at high altitudes. Multifactor logistic regression was performed to determine associations and AF risk factors. SCN5A-H558R genotypes differed significantly between the AF and NAF groups (P < .0125) and the G allele was an independent AF risk factor (P < .05) at both altitudes, with no significant differences according to altitude (P > .0125). At middle altitudes, age, red blood cell distribution width (RDW-SD), left atrial internal diameter (LAD), and G allele were independent AF risk factors. At high altitudes, age, smoking, hypertension, RDW-SD, free triiodothyronine, LAD, and G allele were independent AF risk factors (P < .05). The G allele of SCN5A-H558R might be an independent risk factor of AF both high and middle altitude, but there are some differences in other clinical risk factors of AF.

Abstract 13949: Age-Dependent Detection of Atrial Fibrillation With Implantable Cardiac Monitors in Patients With Cryptogenic Stroke

Introduction: Prolonged and intensified rhythm monitoring is recommended to detect atrial fibrillation (AF) in patients with cryptogenic stroke (CS). Continuous monitoring using implantable cardiac monitors (ICM) results in AF detection rates of up to 30%. Although higher age has been identified as an independent risk factor for AF after CS, there are no specific recommendations for the implantation of ICM in younger patients. Hypothesis: AF dectection in young patients (&lt; 60 years) with CS and continuous rhythm monitoring is low. Methods: From 02/2014 to 11/2021, 186 patients (mean age 65 ± 12 years) with cryptogenic stroke were included in this analysis. All patients underwent 72-h ECG monitoring, transcranial Doppler Ultrasound and transthoracic echocardiography according to current guidelines. Follow-up was performed by means of a regular outpatient presentation every three months and included medical history, physical examination, and interrogation of the ICM. AF was defined as any episode of absolute arrhythmia &gt;30 seconds. Results: AF was detected in 62 patients (33 %) during a mean follow-up of 36 ± 23 months. AF was found in 6 % (3/52), 27 % (17/62), 56 % (31/55) and 65 % (11/17) (p &lt; 0.001) in patients aged &lt; 60 years, 60-69 years, 70-79 years and ≥ 80 years, respectively (see Figure 1). All patients with AF under 60 years had an impaired systolic left ventricular function (left ventricular ejection fraction &lt; 50 %). Conclusions: In cryptogenic stroke patients, detection of Atrial Fibrillation by implantable cardiac monitors increases with advanced age. In patients younger than 60 years, Atrial Fibrillation was only detected in patients with impaired systolic left ventricular function. The diagnostic benefit of ICM implantation in young patients with cryptogenic stroke and preserved LV function is limited. Possibly positive predictors for AF detection should be identified and considered in the decision to implant cardiac monitors.

Increased risk of atrial fibrillation in patients with uterine fibroids: a nationwide population-based study

Abstract Background Uterine fibroid, the most common benign neoplasm of the uterus, is associated with an elevated risk of cardiovascular disease. The link between incident atrial fibrillation (AF) and the uterine fibroid is unclear because earlier studies focused primarily on the development of atherosclerosis and hypertension. We aimed to investigate the risk of AF in patients with uterine fibroid. Methods This is a retrospective cohort study using the Korean National Health Insurance Service database (NHIS). From 2009 to 2012, a total of 2,574,349 women (20 to 40 years old) who underwent general health examinations were included. Diagnosis of uterine fibroids and surgical treatment status was defined by the international classification of diseases, 10th revision codes, and procedural codes from the Korean NHIS. The primary outcome was newly diagnosed AF. The risk of AF according to the uterine fibroids and their surgical treatment status was evaluated using Cox proportional-hazard models. Results Of the total population, the mean age was 29.76±4.27 years, and 20,682 (0.8%) were identified to have uterine fibroid. Incident AF was identified in 3,868 patients (61 in the fibroid group, 3,807 in the control group) during a mean follow-up of 7.3±1.1 years. Patients of the uterine fibroid group showed a higher incidence of AF compared to the control group (0.41 and 0.20 per 1000 person-years, respectively, Figure 1). Multivariate Cox-regression analysis presented that uterine fibroid was an independent risk factor of AF: hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.16–1.93, p=0.002. Compared to the control group, uterine fibroid patients who underwent surgical treatment tend to show a lower risk for AF (HR 1.22, 95% CI 0.79–1.90) than patients without surgical treatment (HR 1.69, 95% CI 1.24–2.30), though statistical significance was indeterminate (Figure 2). After propensity score matching, patients of the uterine fibroid group showed higher risk of AF when compared to the control group (HR 1.77, 95% CI 1.32–2.63, p&amp;lt;0.001), which was in line with our main results. The presence of uterine fibroid was consistently associated with higher risk of AF among all subgroups except for the stroke subgroup. Conclusion Patients with uterine fibroids are predisposed to an increased risk of AF compared to the control group. Careful monitoring of arrhythmia development would be warranted in patients of uterine fibroid and surgical treatment as it is associated with a modest risk decrement of incident AF. Funding Acknowledgement Type of funding sources: None.

The Arf6/PIP5K pathway activates IKACh in cigarette smoke mediated atrial fibrillation

Cigarette smoking (CS) is a major cause of cardiovascular diseases. Smokers are at a significantly higher risk for developing atrial fibrillation (AF), a dangerous and abnormal heart rhythm. In the US, 15.5% of adults are current smokers, and it is becoming clear that CS is an independent risk factor for AF, but a detailed mechanistic understanding of how CS contributes to the molecular patho-electrophysiology of AF remains elusive. We investigated if CS related AF is in part mediated through a mechanism that depends on the cardiac acetylcholine activated inward rectifier potassium current (IKACh). We tested the hypothesis that CS increases IKACh via phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5K) and ADP ribosylation factor 6 (Arf6) signaling, leading to AF perpetuation. In vivo inducibility of AF was assessed in mice exposed to CS for 8 weeks. AF duration was increased in CS exposed mice, and TertiapinQ, an IKACh blocker prevented AF development in CS exposed mice. In HEK293 cells stably transfected with Kir3.1 and Kir3.4, the molecular correlates of IKACh, CS exposure increased the expression of the Kir3.1 and Kir3.4 proteins at the cell surface, activated Arf6 and increased the IKACh current. Inhibition of PIP5K, or of Kir3.1/Kir3.4 trafficking via Arf6 abrogated the CS effects on IKACh. Cigarette smoke modifies the atrial electrophysiological substrate, leading to arrhythmogenesis, in part, through IKACh activation via an Arf6/PIP5K dependent pathway.

The effect of apolipoprotein E gene polymorphism and Lp(a) levels on coronary artery disease with atrial fibrillation.

ObjectiveTo explore the influence of apolipoprotein E (APOE) genotypes and blood lipid metabolism on coronary artery disease (CAD) with atrial fibrillation (AF).MethodsPatients with suspected CAD were consecutively enrolled and divided into groups with or without CAD and/or AF. Blood lipid levels and APOE genotypes were determined and analysed for associations with CAD and AF.ResultsA total of 2048 patients were included (400 patients without CAD or AF [controls], 126 patients without CAD but with AF, 1294 patients with CAD without AF, and 228 patients with CAD and AF). Age and lipoprotein (a) (Lp[a]) levels were significantly higher in patients with CAD and AF versus those with CAD without AF. Among patients with CAD, the E3/E3 genotype and ε3 allele frequencies were significantly lower in patients with AF than in those without AF, and the E4/E4 genotype and ε4 allele frequencies were significantly increased. Multivariate logistic regression revealed that increased Lp(a) levels and age were independent risk factors for AF in patients with CAD.ConclusionAmong patients with CAD, those with AF had increased age, ε4 frequencies and Lp(a) levels. Age and Lp(a) levels may be independent risk factors for AF in patients with CAD.

Migraine with aura associates with a higher artificial intelligence: ECG atrial fibrillation prediction model output compared to migraine without aura in both women and men.

To compare the artificial intelligence-enabled electrocardiogram (AI-ECG) atrial fibrillation (AF) prediction model output in patients with migraine with aura (MwA) and migraine without aura (MwoA). MwA is associated with an approximately twofold risk of ischemic stroke. Longitudinal cohort studies showed that patients with MwA have a higher incidence of developing AF compared to those with MwoA. The Mayo Clinic Cardiology team developed an AI-ECG algorithm that calculates the probability of concurrent paroxysmal or impending AF in ECGs with normal sinus rhythm (NSR). Adult patients with an MwA or MwoA diagnosis and at least one NSR ECG within the past 20 years at Mayo Clinic were identified. Patients with an ECG-confirmed diagnosis of AF were excluded. For each patient, the ECG with the highest AF prediction model output was used as the index ECG. Comparisons between MwA and MwoA were conducted in the overall group (including men and women of all ages), women only, and men only in each age range (18 to <35, 35 to <55, 55 to <75, ≥75 years), and adjusted for age, sex, and six common vascular comorbidities that increase risk for AF. The final analysis of our cross-sectional study included 40,002 patients (17,840 with MwA, 22,162 with MwoA). The mean (SD) age at the index ECG was 48.2 (16.0) years for MwA and 45.9 (15.0) years for MwoA (p < 0.001). The AF prediction model output was significantly higher in the MwA group compared to MwoA (mean [SD] 7.3% [15.0%] vs. 5.6% [12.4%], mean difference [95% CI] 1.7% [1.5%, 2.0%], p < 0.001). After adjusting for vascular comorbidities, the difference between MwA and MwoA remained significant in the overall group (least square means of difference [95% CI] 0.7% [0.4%, 0.9%], p < 0.001), 18 to <35 (0.4% [0.1%, 0.7%], p=0.022), and 35 to <55 (0.5% [0.2%, 0.8%], p < 0.001), women of all ages (0.6% [0.3%, 0.8%], p < 0.001), men of all ages (1.0% [0.4%, 1.6%], p=0.002), women 35 to <55 (0.6% [0.3%, 0.9%], p < 0.001), and men 18 to <35 (1.2% [0.3%, 2.1%], p=0.008). Utilizing a novel AI-ECG algorithm on a large group of patients, we demonstrated that patients with MwA have a significantly higher AF prediction model output, implying a higher probability of concurrent paroxysmal or impending AF, compared to MwoA in both women and men. Our results suggest that MwA is an independent risk factor for AF, especially in patients <55 years old, and that AF-mediated cardioembolism may play a role in the migraine-stroke association for some patients.

Homocysteine and atrial fibrillation: novel evidences and insights.

Atrial fibrillation (AF) is one of the most prevalent rhythm disorders worldwide, with around 37.574 million cases around the globe (0.51 % global population). Different studies showed a high informative value of different biomarkers, including such related to the systemic inflammation, biomechanical stress and fibrosis. In this review article we aimed to study only the relation of homocysteine to the AF development. Homocysteine is a sulfur-containing amino acid, that is produced in the process of methionine metabolism. Which is a non-canonical amino acid, that is derived from the food proteins. From the scientific point of view there is a relation between hyperhomocysteinemia and myocardial fibrosis, but these mechanisms are complicated and not sufficiently studied. Homocysteine regulates activity of the ion channels through their redox state. Elevated homocysteine level can condition electrical remodeling of the cardiomyocytes through the increase of sodium current and change in the function of rapid sodium channels, increase of inwards potassium current and decrease in amount of rapid potassium channels. High homocysteine concentration also leads to the shortening of the action potential, loss of the rate adaptation of the action potential and persistent circulation of the re-entry waves. In a series of experimental studies on mice there was an association found between the homocysteine level and activity of vascular inflammation. Elevation of homocysteine level is an independent factor of the thromboembolic events and AF relapses. Population studies showed, that homocysteine is an independent risk factor for AF. So, homocysteine is an interesting target for up-stream therapy.

Higher heart rate variability as a predictor of atrial fibrillation in patients with hypertension

The autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF). However, the meaning of higher heart rate variability (HRV) in predicting AF remains unclear. Among 2100 patients in the Holter registry, a total of 782 hypertensive patients were included in this study. Baseline HRV was measured by time domain and frequency domain methods using 24-h Holter monitoring. The primary outcome was the development of AF. During an average follow-up of 1.1 years, 44 patients developed AF. Higher HRV parameters including high-frequency (P < 0.001), the square root of the mean squared differences of successive NN intervals (P < 0.001), and the percentage of NN intervals that are more than 50 ms different from the previous interval (P < 0.001) were associated with the occurrence of AF in univariate analysis. Premature atrial contractions burden, lower baseline heart rate, age, hemodialysis, coronary artery disease, and chronic heart failure were also associated with AF. In Cox regression analysis, higher HRV (representing excessive autonomic fluctuation) was an independent risk factor for AF. Excessive autonomic fluctuation represented by higher HRV in patients with hypertension was associated with an increased risk of AF.

Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers.

Alcohol-a risk factor for atrial fibrillation (AF)-is metabolized by aldehyde dehydrogenase 2 (ALDH2). Dysfunctional alleles of ALDH2 (ALDH2-deficient variants) are prevalent among East Asians. Because the prevalence of AF is estimated to be high in ALDH2-deficient variant carriers, we investigated the correlation between AF and ALDH2-deficient variant carriers, including the association with habitual alcohol consumption. A total of 656 consecutive patients were included in this investigation. ALDH2 genotypes were divided into ALDH2 homozygous wild-type (∗1/∗1), ALDH2 heterozygous-deficient allele (∗1/∗2), and ALDH2 homozygous-deficient allele (∗2/∗2). Multivariate analyses were applied to determine the correlation between ALDH2 genotype and AF. ALDH2∗1/∗2 and ALDH2∗2/∗2 carriers who were ALDH2-deficient variant carriers comprised 199 (30.3%) and 27 (4.1%) patients, respectively. Among these patients, the proportions of habitual alcohol consumption were 26.1% and 0%, respectively. Multivariate analysis revealed that ALDH2∗1/∗2 itself was not a risk factor for AF (odds ratio [OR]: 1.28; P=0.21). However, habitual alcohol consumption in ALDH2∗1/∗2 carriers was an independent risk factor of AF (OR:4.13; P=0.001). Contrary to expectations, ALDH2∗2/∗2 itself had a lower incidence of AF among other risk factors (OR: 0.37; P=0.03). Although the ALDH2∗1/∗2 itself was not associated with AF, ALDH2∗1/∗2 carriers with habitual alcoholconsumption could experience AF because of slow alcohol metabolism. In contrast, ALDH2∗2/∗2 itself had a lower incidence of AF. This might be related to the absence to habitual alcohol consumption in ALDH2∗2/∗2 carriers because ofthe negligible activity of ALDH2. Thus, abstaining from alcohol consumption might prevent the development of AF in patients who are ALDH2∗1/∗2 carriers.

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation, Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD. Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles). ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001]. ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.