Prevention Of Atrial Fibrillation Research Articles

Assessing the Predictive Value of the SAMe-TT2R2 Score for Poor Anticoagulation Control in a Diverse Ethnic Population.

Introduction: In Asian countries, warfarin is still widely used for stroke prevention in non-valvular atrial fibrillation compared to non-vitamin K antagonist oral anticoagulants (NOACs) due to its affordability. A tool such as the SAMe-TT2R2 is needed to determine the probability of achieving and maintaining good anticoagulation control with warfarin therapy. However, it requires validation in the Malaysian cohort. Therefore, the objective of our study is to validate the SAMe-TT2R2 score in predicting poor anticoagulation control in Malaysia. A time in therapeutic range (TTR) < 65% was used to determine poor anticoagulation control. Method: This retrospective cohort study was conducted from July 2022 to July 2023. Patients were enrolled in 2020 from 49 facilities located across Malaysia resulting in a total of 957 included patients. TTR was calculated using Roseendaal's method. Results: The mean (SD) TTR and SAMe-TT2R2 score in the overall cohort is 65.2% (±24) and 5.5 (±0.9) respectively. Almost half of the population (43.7%) has the SAMe-TT2R2 score of 5. Having diabetes, ischemic heart disease, and increasing HAS-BLED and SAMe-TT2R2 score affects anticoagulation control on univariate analysis. However, after adjusting for demographics and clinical variables on multivariate analysis, only the SAMe-TT2R2 score as a continuous variable persists in predicting poor anticoagulation control. A SAMe-TT2R2 score cut-off point of >5 best predicts poor anticoagulation control with a sensitivity of 0.49 and a specificity value of 0.68. Conclusion: The SAMe-TT2R2 score, especially when exceeding 5, was associated with a higher likelihood of poor anticoagulation control, emphasizing its relevance in clinical assessment. However, its limited predictive capability, reflected by a C-statistic of 0.548, suggests the need for cautious interpretation and consideration of additional factors in anticoagulation management decisions. Continuous monitoring and personalized strategies are crucial for optimizing outcomes in this population.

Artificial intelligence–derived electrocardiographic aging and risk of atrial fibrillation: a multi-national study

Abstract Background and Aims Artificial intelligence (AI) algorithms in 12-lead electrocardiogram (ECG) provides promising age prediction methods. This study investigated whether the discrepancy between ECG-derived AI-predicted age (AI-ECG age) and chronological age, termed electrocardiographic aging (ECG aging), is associated with atrial fibrillation (AF) risk. Methods An AI-ECG age prediction model was developed using a large-scale dataset (1 533 042 ECGs from 689 639 participants) and validated with six independent and multi-national datasets (737 133 ECGs from 330 794 participants). The AI-ECG age gap was calculated across two South Korean cohorts [mean (standard deviation) follow-up: 4.1 (4.3) years for 111 483 participants and 6.1 (3.8) years for 37 517 participants], one UK cohort [3.0 (1.6) years; 40 973 participants], and one US cohort [12.9 (8.6) years; 90 639 participants]. Participants were classified into two groups: normal group (age gap &amp;lt; 7 years) and ECG-aged group (age gap ≥ 7 years). The predictive capability of ECG aging for new- and early-onset AF risk was assessed. Results The mean AI-ECG ages were 51.9 (16.2), 47.4 (12.5), 68.4 (7.8), and 56.7 (14.6) years with age gaps of .0 (6.8), −.1 (6.0), 4.7 (8.7), and −1.4 (8.9) years in the two South Korean, UK, and US cohorts, respectively. In the ECG-aged group, increased risks of new-onset AF were observed with hazard ratios (95% confidence intervals) of 2.50 (2.24–2.78), 1.89 (1.46–2.43), 1.90 (1.55–2.33), and 1.76 (1.67–1.86) in the two South Korean, UK, and US cohorts, respectively. For early-onset AF, odds ratios were 2.89 (2.47–3.37), 1.94 (1.39–2.70), 1.58 (1.06–2.35), and 1.79 (1.62–1.97) in these cohorts compared with the normal group. Conclusions The AI-derived ECG aging was associated with the risk of new- and early-onset AF, suggesting its potential utility to identify individuals for AF prevention across diverse populations.

The Effect of Silymarin on the Prevention of Atrial Fibrillation After Coronary Artery Bypass Grafting.

Postoperative atrial fibrillation is a frequent complication after coronary artery bypass grafting and is associated with increased mortality. The effects of various drugs on the occurrence of postoperative atrial fibrillation have been studied, but no one has looked into the effect of silymarin on the occurrence of postoperative atrial fibrillation. This prospective experimental study included 160 patients undergoing coronary artery bypass grafting. The experimental group received 400 mg of silymarin orally three days before the surgery, while the control group did not. The occurrence of postoperative atrial fibrillation was monitored. Patients' clinical data and postoperative characteristics were investigated to elucidate their impact on postoperative atrial fibrillation. Postoperative atrial fibrillation occurred in significantly fewer patients in the experimental group (14 vs. 30, P=0.008). There were also lower mean values of postoperatively measured C-reactive protein (P<0.0005) and aspartate aminotransferase (P=0.001) in the experimental group. Within the multivariate regression model, a non-silymarin group (odds ratio 0.296 [0.109-0.807], P=0.005), postoperative red blood cell transfusion (odds ratio 5.218 [1.930-14.107], P=0.001), left atrial diameter (odds ratio 7.800 [2.122-28.672], P=0.002), postoperative C-reactive protein (odds ratio 1.020 [1.008-1.032], P=0.001), and CHA₂DS₂-VASc score (standing for congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74 years, and sex category [female]) (odds ratio 1.873 [1.279-2.743], P=0.001) proved to be independently associated with the development of postoperative atrial fibrillation. This study showed that preoperative administration of silymarin significantly reduces the development of atrial fibrillation after coronary artery bypass grafting.

European Society of Cardiology (ESC) guidelines on atrial fibrillation 2024 : What is new and what is important?

The 2024 guidelines of the European Society of Cardiology (ESC) on atrial fibrillation (AF) present current and comprehensive recommendations for the diagnosis, prevention and treatment of AF. They are based on the AF-CARE treatment pathway, which includes modification of cardiovascular risk factors, stroke prevention, symptom management and continuous re-evaluation. Accordingly, all patients with newly diagnosed AF should undergo transthoracic echocardiography. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended for the treatment of heart failure across all clinical and echocardiographic levels of left ventricular ejection fraction (LVEF). The CHA2DS2-VASc score has been simplified to the CHA2DS2-VA score for the risk assessment of thromboembolism. For rate or rhythm control pharmacotherapy with beta-blockers, digitalis, amiodarone and flecainide are still the most important drugs. Pulmonary vein isolation is now also recommended as afirst-line treatment for paroxysmal AF. Re-evaluation of risk factors and treatment of comorbidities is also emphasized. Overall the guidelines represent a further development and update based on recent studies. They remain practical and provide clear and detailed recommendations for action that are globally recognized in the clinical practice.

25-year trajectories of physical activity and atrial fibrillation risk: results from the ARIC study

BackgroundThe relationship between serial changes in physical activity and the risk of developing atrial fibrillation (AF) has been rarely studied.ObjectivesTo evaluate the association between changes in physical activity over time and the incidence of AF.MethodsA total of 11,828 participants without AF at baseline (visit 1: 1987–1989) from the ARIC Study were included. Physical activity was measured using the modified Baecke Physical Activity Questionnaire at three different visits between 1987 and 2013. Physical activity trajectories over 25 years were identified using latent class trajectory modeling. The primary outcome was the incidence of AF. Multivariable Cox hazard regression models were used to evaluate the relationship between physical activity trajectories and the incidence of AF.ResultsOver a median follow-up of 24 years, 2,108 AF cases (17.8%) occurred. Four distinct physical activity trajectories were identified: light [n = 5,266 (43.3%)]; reduced moderate [n = 3,583 (29.0%)]; moderate [n = 2,691 (25.0%)]; and vigorous intensity [n = 288 (2.8%)]. Compared to the light group, the hazard ratio (HR) and 95% confidence interval (CI) for AF were 1.18 (1.07–1.30) (p &amp;lt; 0.001) for the reduced moderate group, 0.61 (0.53–0.70) (p &amp;lt; 0.001) for the moderate group, and 0.82 (0.59–1.12) (p = 0.21) for the vigorous group, after multivariate adjustments.ConclusionMaintaining moderate levels of physical activity is associated with a lower risk of AF, while a decrease in activity from moderate to light levels increases the risk. These findings highlight the importance of sustaining adequate physical activity levels for the prevention of AF.

JTH in Clinic – Choosing the optimal oral anticoagulant for stroke prevention in atrial fibrillation: direct oral anticoagulants vs. vitamin K antagonists

Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) for stroke prevention in many patients with atrial fibrillation (AF) but VKAs may still be preferred in some situations. We use a case-based approach to present the evidence for the possible use of a VKA in preference to a DOAC in patients with AF and rheumatic mitral stenosis, high body mass index, frailty and with breakthrough stroke despite being prescribed a DOAC.

Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

Although most patients with atrial fibrillation (AF) receiving a direct oral anticoagulant (DOAC) do not require drug concentration measurements, there are situations where such information could be useful. Existing guidance documents provide usual on-therapy ranges for drug concentrations, but these have important limitations. This is a systematic review and meta-analysis of studies reporting trough and peak levels of DOAC regimens approved for stroke prevention in AF. We used random effects models and the quantile estimation method to estimate the median and a usual on-therapy range (10th and 90th percentiles). Of 4,822 unique publications, 53 studies met eligibility (29,266 trough and 12,103 peak levels). Usual on-therapy ranges for trough levels were 38 to 155 and 58 to 206 ng/mL for apixaban 2.5 and 5 mg twice daily; 35 to 138 and 33 to 151 ng/mL for dabigatran 110 and 150 mg twice daily; 8 to 54 and 13 to 66 ng/mL for edoxaban 30 and 60 mg daily; and 16 to 74 and 19 to 72 ng/mL for rivaroxaban 15 and 20 mg daily. The corresponding range for peak levels were 96 to 251 and 132 to 343; 65 to 223 and 76 to 285; 57 to 219 and 127 to 407; 131 to 384, and 169 to 313 ng/mL, respectively. This systematic review and meta-analysis provides updated and more representative usual on-therapy ranges of DOAC levels in patients with AF.

Abstract 4136743: Current Oral Anticoagulation Use Among Patients With Atrial Fibrillation and Risk Factors Associated With Inadequate Treatments: A Report From a UK Population Cohort Study

Background: The worldwide prevalence of atrial fibrillation (AF) continues to grow with approximately 60 million cases each year. Aim: To understand demographic and clinical attributes of patients receiving adequate DOAC (direct oral anticoagulant) treatment, DOAC undertreatments, or no OAC (oral anticoagulant) treatments, thus providing valuable perspectives into the current landscape of stroke prevention in AF within the UK. Methods: We used the Clinical Practice Research Datalink (CPRD) Aurum database from January 2020 to March 2021 for this retrospective observational study. Patients’ characteristics from various cohorts (standard dose [SD], low dose [LD] per label, LD inconsistent per label prescribing, and untreated) were evaluated based on OAC treatment. Duration of index OAC treatment, time to discontinuation and incidence rates across OAC treated cohorts were assessed. A machine learning method (Elastic Net) identified factors associated with being undertreated or untreated. Results: The final sample included 13,341 patients (mean age 78.5 and female 47%). Within a 180-day timeframe post-diagnosis, 76% of patients received OAC treatment, while 24% did not receive any OAC therapy. Among those treated with DOAC (n=9947), 74% were administered SD (n=7238), 18% received LD per labels (n=1756) and 10% were inappropriately prescribed LD of DOACs (n=953). Both LD cohorts tended to have shorter duration of OAC therapy (figure) and higher discontinuation rates (per 100 person-years; LD per label: 42.97; LD not per label: 39.11) compared to the SD cohort (SD: 31.67). Patients who were untreated were associated with elevated bleeding risk factors such as renal disease and prior bleeding history; patients who received inappropriate LD were associated with age above 75, renal disease, GI conditions with PPI (proton pump inhibitor) concomitant treatments when compared to SD cohort. Conclusions: In our study, a considerable proportion of AF patients remained untreated/undertreated and were associated with bleeding risk factors, highlighting the unmet needs within this population. Exploring potential alternative treatment options with enhanced safety profiles could offer substantial benefits to patients in need.

Abstract 4129195: Mechanisms of Healthy Aging in the Prevention of Atrial Fibrillation

Introduction: Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia. AF can lead to severe complications such as myocardial infarction, strokes, and sudden death. With 70% of AF patients aged 65 and older, aging stands as the major risk factor for AF. Our group have recently contributed to reveal that old Wistar rats (20 months) are more susceptible to AF than younger rats (5 months). Interestingly, Lou/c/jall (LOU) rats, a model of healthy aging derived from Wistar rats, can live up to ~35 months old (equivalent to 100 human years). LOU rats have been identified as resistant to age-related diseases such as obesity, hypertension, and neurodegenerative disorders, which are major risk factors for AF. However, the susceptibility of LOU rats to AF have never been reported. Hypothesis: LOU rats may carry specific molecular adaptations conferring resistance to age-related cardiac remodeling and low AF vulnerability. Objectives: Characterize the vulnerability of very old LOU rats (32 months) to AF compared to old Wistar rats (22 months). Determine the atrial inflammatory profile of LOU rats and identify the molecular adaptations that may explain their resistance to AF Methods: Male and Female rats were divided into five groups: LOU and Wistar rats of 5 months (young), 20 months (old), and 32 months (very old: LOU/c rats only). AF inducibility was assessed in vivo using transesophageal electrophysiological study and cardiac structure and function were analyzed by in vivo echocardiography. Atrial electrical conduction was examined using ex vivo optical mapping. Histological analyses were performed to assess atrial fibrosis. Additionally, immunoblot analysis, qPCR, and RNA sequencing were employed to investigate the levels of biomarkers involved in atrial inflammation and fibrosis. Result: Old Wistar rats were more vulnerable to AF than young rats. Old and very old LOU were significantly more resistant to AF than old Wistar animals. LOU rats’ low susceptibility to AF was accompanied with absence of cardiac structural and functional remodeling and low levels of atrial fibrosis compared to old Wistar. Additionally, advanced age did not affect LOU rats’ atrial electrical conduction properties as compared to old Wistar rats. Conclusion: Promotion of healthy aging conditions mimicking LOU rats’ resistance to cardiac remodeling and reduction of atrial fibrosis may contribute to prevent AF in subjects with pathological aging.

Abstract 4141454: Atrial Fibrillation in American Indians: Comparative Analysis of Characteristics and Anticoagulation Use for Stroke Prevention of Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting individuals of all races. Anticoagulation (AC) therapy is recommended by the guidelines to reduce the risk of stroke in AF patients. Previous reports indicate that American Indians (AI) have a higher risk of AF and an increased risk of stroke from AF. Aim: To describe the demographic and clinical characteristics of the AI population with AF and compare their AC status with other racial groups. Methods: We retrospectively analyzed AF patients age &gt;18 years hospitalized between January 2022 and October 2023 in two hospitals serving a large Navajo Nation AI population in rural Northern Arizona. We compared baseline characteristics, AC status and direct oral anticoagulant (DOAC) use between AI and other races. Between group statistical analysis was completed using a chi-square for categorical variables and a Mann-whiney U test for continuous variables, with statistical significance defined as a p-value ≤ 0.05. Results: In total, 9255 patients were admitted with AF: 871 (9.4%) were AI, with 696 (79.9%) being Navajo Nation AI and 8284 (89.5%) from other non-AI races. AI patients with AF were younger (average age 65±15.9 vs 75±11.2; p &lt;0.0001), had fewer female patients (30.5% vs 39.3%; p &lt;0.0001), and were less likely to be treated with oral anticoagulation (40.5% vs 50.9%; p &lt;0.0001; OR 0.66; 95% CI: 0.57 to 0.76) compared to non-AI races (table 1). Among those anticoagulated, AI patients were less likely to receive a DOAC (38.0% vs 44.7%; p = 0.0002; OR 0.76; 95% CI: 0.66 to 0.88) compared to non-AI races (table 2). Conclusions: Our analysis, with a significant number of AI pts, reveal that AI patients develop AF at a younger age and despite an increased risk of stroke, have significantly lower rates of anticoagulation use, particularly with DOACs. Our findings underscore the need for guideline-adherent AC use in this AI population.

Abstract 4113188: Increased Physical Activity Intensity Associated with Reduced Risk of Atrial Fibrillation among Older Adults in South Korea: A Retrospective Cohort Study

Introduction: Physical activity (PA) may be associated with a lower risk of atrial fibrillation (AF), but this relationship remains controversial. In particular, further research is needed on the association between changes in PA intensity and AF risk among older adults. Hypothesis: We hypothesized that an increase in PA intensity would be associated with a reduced risk of AF among older adults aged 65 years and older in South Korea. Aim: This cohort study aimed to evaluate the association between changes in metabolic equivalent tasks (METs)-min/week and the risk of AF in the elderly using a nationally representative database. Methods: We conducted a retrospective cohort study using the Korea National Health Insurance Service (KNHIS) database. This cohort included 1,726,697 individuals aged 65 years and older without a history of cardiovascular disease diagnosis who underwent two consecutive health screening examinations from 2009 to 2012. PA was defined as MET-min/week derived from two consecutive health examinations during 2009-2010 (1st period) and 2011-2012 (2nd period), respectively. The primary outcome was an AF diagnosis during the follow-up period from 2013 to 2021. We estimated the sub-distribution hazard ratio (sHR) and 95% confidence interval (CI) for the association of changes in PA intensity with AF using Fine-Gray sub-distribution hazard models after adjustment for covariates. Results: This study included 1,726,697 participants (mean age 71.08; 46.78% male). An increase in PA intensity was associated with a reduced risk of AF (P for trend&lt;0.001). Compared to persisting in physical inactivity, a change in PA intensity from physically inactive to ≥1000 MET–min/week was associated with a lower risk of AF (sHR, 0.83, 95% CI, 0.81-0.85). In contrast, a change in PA intensity from ≥1000 MET–min/week to being physically inactive was associated with a higher risk of AF (sHR, 1.30, 95% CI, 1.27-1.33) as compared to persistence in ≥1000 MET–min/week of PA intensity. Conclusions: An increase in MET-min/week may be associated with a reduced risk of AF among adults aged 65 years and older. Therefore, interventions encouraging PA should be recommended to maximize the health benefits of AF prevention in the elderly.

Prevention of Atrial Fibrillation using Vaughan Williams Class IC Drugs for Multiple Premature AtrialContractions: A Clinical Observational Study

Background: Atrial fibrillation (A-Fib) poses a significant clinical challenge, particularly in the elderly and those with hypertension. If A-Fib represents one stage in the spectrum of electrical degeneration caused by aging-induced remodeling of the left atrial wall, catheter ablation is not an essential treatment. The efficacy of Vaughan Williams Class IC drug in preventing the progression of multiple premature atrial contractions (mPAC) toward paroxysmal atrial fibrillation (PAF) and A-Fib in the earlier stage of histological change was investigated. Method and results: Group A (4 patients with mPAC) and Group B (9 patients with PAF) were treated with Class IC drugs. Treatment outcomes were compared between these two Groups and Group C (8 patients with chronic A-Fib). Follow-up assessments were performed to evaluate the maintenance of sinus rhythm. All mPAC patients maintained sinus rhythm during the follow-up period. In the PAF group, 8 out of 9 patients maintained their sinus rhythm. Conclusion: Early treatment with Class IC drugs shows promise in preventing the progression of A-Fib and maintaining sinus rhythm in patients with mPAC and PAF. These findings highlight the potential role of pharmacological therapy in delaying the onset of A-Fib, thereby improving clinical outcomes and reducing the need for invasive procedures such as ablation.

Symptoms Burden as a Clinical Outcomes Assessment in HeartFailure Patients With Atrial Fibrillation.

Safe and effective pharmacologic therapy for atrial fibrillation (AF) in heart failure (HF) is an unmet need. In AF clinical trials, the standard primary endpoint of time to first symptomatic AF event (TTFSE) has several disadvantages, which could theoretically be overcome by measurement of AF-specific symptoms burden during an entire follow-up period. The authors sought to develop and validate a method of measuring symptom burden of AF in a HF population. The authors constructed a patient-reported outcome instrument (Atrial Fibrillation Symptoms Questionnaire [AFSQ]) to function in the setting of AF/HF, and used it to measure symptoms throughout long-term follow-up. The AFSQ queries the presence of 10 new or worsening symptoms, equally divided between those associated with AF or HF. In a 267 patient AF/HF trial comparing 2 AF prevention treatments, the AFSQ was linked to electrocardiography documented AF to form a 2-component clinical outcome assessment (SxBAF) that was subjected to psychometric testing, anchor validation, and endpoint efficiency comparison to TTFSE. SxBAF exhibited greater efficiency than time to first symptomatic event for treatment difference detection, resulting in smaller projected clinical trial sample sizes. SxBAF correlated well with device-detected AF burden (Spearman's ρ=0.74; P< 0.0001), while permitting gradation in symptom severity. SxBAF also identified treatment group differences in cardiovascular serious adverse events and AF interventions and in recent-onset AF provided specificity for AF- or worsening HF-associated symptoms (P< 0.001 for each). Measurement of symptoms burden throughout clinical trial follow-up is feasible in AF/HF and should be useful for evaluating patient-centered outcomes in AF prevention trials. (Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With HeartFailure [GENETIC-AF]; NCT01970501).

Factors related to the choice of warfarin for treating newly diagnosed nonvalvular atrial fibrillation are associated with safety outcomes during anticoagulation: A new‐user, active‐comparator, retrospective cohort study

AbstractBackgroundDirect oral anticoagulants (DOACs) are preferred for stroke prevention in nonvalvular atrial fibrillation (NVAF); however, warfarin is still used. This study examined why physicians may choose warfarin over DOACs and the associated safety outcomes in patients with NVAF.MethodsWe conducted a new‐user, active‐comparator cohort study in newly diagnosed patients with NVAF to assess safety outcomes after the introduction of DOACs in Japan.ResultsThe median observation period was 1120 days; 1428 patients started anticoagulation therapy with warfarin and 1551 with DOACs. Warfarin was chosen for patients with lower creatinine clearance and left ventricular ejection fractions and those using aspirin and verapamil. The unadjusted risk of major bleeding was considerably higher in the warfarin group but was nonsignificant after adjusting for variables associated with the choice of warfarin, in addition to age and sex. The risk of death was higher in the warfarin group, even after adjustments for relevant variables. However, high‐risk subgroups, including those with older ages and multiple comorbidities, such as renal impairment, for whom warfarin was more likely to be selected, had severely compromised prognoses with either anticoagulant. The risk of stroke/systemic embolism was not significantly different between the two groups.ConclusionsWarfarin is often chosen for older patients with multiple comorbidities characterized by reduced renal function, which is associated with a higher risk of major bleeding and mortality. These high‐risk patients seem to have a poor prognosis regardless of the type of anticoagulant used. Thus, safe anticoagulant therapy remains a challenge for such patients.

Lipid-lowering drugs, circulating inflammatory factors, and atrial fibrillation: a mediation Mendelian randomization study.

Previous studies have shown an association between lipid-lowering drugs, circulating inflammatory factors, and atrial fibrillation (AF), but the specific effects of lipid-lowering drugs on AF and whether they can be mediated by circulating inflammatory factors remain unclear. We collected 10 genetic variants encoding lipid-lowering drug targets (LDLR, HMGCR, PCSK9, NPC1L1, APOB, APOB, ABCG5, ABCG8, LPL, APOC3, and PPARA) and AF based on genome-wide association study (GWAS) summary statistics. Drug target Mendelian randomization (MR) was used to explore the causal relationship between lipid-lowering drugs and AF. In addition, we performed a mediation analysis of 91 circulating inflammatory factors to explore potential mediators. Sensitivity analyses were performed to verify the reliability of the MR Results by MR-Egger intercept test, Cochran's Q test and leave-one-out test. The results of IVW method showed that LPL agonist had a protective effect on AF(OR = 0. 854, 95%CI: 0.816-0.894, P = 1.844E-11). However, the other nine lipid-lowering drug targets had no significant effect on AF. Notably, we found a mediator role of Fibroblast Growth Factor 5 (FGF5) in the protective effect of LPL agonist on AF with a mediator ratio of 9.22%. Sensitivity analyses supported the robustness of our findings, indicating a possible mediating pathway by which LPL agonists affect the risk of AF. Our study provides new insights into the complex interactions among lipid-lowering agents, circulating inflammatory factors and AF, and also identified a potential mediating role of FGF5 in the pathogenesis of AF. Our findings highlight the potential of LPL agonists and targeting specific inflammatory factors for therapeutic intervention in AF, providing promising avenues for future research and clinical strategies for the management and prevention of AF.

Risk factors and prevention of atrial fibrillation in the postoperative period after coronary artery bypass grafting: a literature review

The increasing volume of coronary artery bypass grafting inevitably contributes to a growing number of postoperative complications. Atrial fibrillation (AF) develops in every second or third patient. This complication prolongs inpatient stays and increases costs of the healthcare system. The review presents data on the risk factors for postoperative AF, as well as the proposed methods of prevention and treatment. The research results indicate the role of type 2 diabetes mellitus, obesity, arterial hypertension; among laboratory parameters, mean platelet volume, red blood cell distribution width, C-reactive protein, erythrocyte sedimentation rate, monocyte/high-density lipoprotein cholesterol ratio are of prognostic value. Drug and non-drug methods of prevention and treatment of postoperative AF are discussed. The methods indicated in the presented works showed effectiveness, but had a number of limitations.

From the INVICTUS Trial to Current Considerations: It's Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies-e.g., osocimab, anti-sense oligonucleotides-e.g., fesomersen, and small molecule inhibitors-e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

Plasma trimethylamine-n-oxide associates with reduced hippocampal volume and cognitive impairment in atrial fibrillation

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia in modern society and affected patients appear particularly vulnerable to cognitive dysfunction. Yet, the pathomechanism of this association other than thromboembolism (TE) is not fully understood. We have shown earlier an association of cognitive dysfunction with the gut microbiome derivate trimethylamine-N-oxide (TMAO), which predominantly results from the consumption of red meat. We therefore hypothesized that TMAO may affect hippocampal volume (HV) as a brain structure relevant for cognition. Purpose To demonstrate the structure-function correlation of high TMAO levels with reduced cognitive function and lower HV in a large cohort of patients with atrial fibrillation. Methods We included 1’736 patients with confirmed AF from the Swiss-AF-cohort with both, available blood samples for TMAO measurement and with brain magnetic resonance imaging (bMRI) for the determination of HV at baseline. TMAO levels were measured by liquid chromatography-mass spectrometry (LC-MS). bMRI were obtained by 1.5 or 3 Tesla scanners. HV was assessed by the FreeSurfer software (v 7.4.0) subregion segmentation module and normalized by using Sequence Adaptive Multimodal SEGmentation (SAMSEG) to determine the segmentation based intracranial volume. Patients were divided into TMAO quartiles (Q1: 0.6-3.8, Q2: 3.8-5.5, Q3: 5.5-8.5, Q4: 8.5-164.3μmol/l). Their TMAO levels were compared with their HV (unit = mm3) in linear mixed effect models adjusted for multiple covariates (model 1: age, sex, total intracranial volume (ICV), education level; model 2 = model 1 + smoking status, body mass index (BMI), alcohol consumption, physical activity; model 3 = model 2 + hypertension, coronary artery disease, previous stroke, geriatric depression scale). We assessed both unilateral HV (right = RHV, left = LHV) and bilateral HV standardized by the individual total ICV. Results Overall mean age was 72.5 years (+/-8.4 SD), 27.2% were female. Most of the patients were well educated (39.4% advanced, 48.8% middle education) and 44% never smoked. After multivariable adjustments, patients in the highest TMAO quartile showed a significant reduction of bilateral HV volume of 93.4mm3 (95% CI -179.0 to -7.8, p = 0.03). The RHV appeared more affected and was significantly reduced by 48.2mm3 (CI -93.4, -3.0, p=0.04), whereas LHV was decreased by 44.2mm3 (-89.4, 1.0, p=0.06) in the highest TMAO quartile. Conclusion(s) TMAO negatively associates with bilateral HV in patients with AF. Our results suggest a structure-function-correlation between high TMAO levels and cognitive dysfunction. The findings may be relevant for the high TMAO-exposed patients and advocates for the importance of (possible dietary) prevention in AF.

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P&amp;lt;0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P&amp;lt;0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P&amp;lt;0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

Left atrial enlargement: a crucial indicator for identifying atrial fibrillation in patients with hypertension

Abstract Background Left atrial enlargement resulting from hypertension is closely linked to the development and persistence of atrial fibrillation (AF). The newly proposed staging recognizes AF as disease continuum, which makes us aware that AF prevention should focus on the Pre-AF stage, and atrial enlargement is one of the important manifestations in this stage. Previous scoring systems, such as CHA2DS2-VASc and C2HEST, along with the recently highlighted left atrial diameter (LAD), have been significant tools for predicting AF occurrence. However, a comprehensive assessment of their utility is currently lacking. Purpose This study aims to explore the role of left atrial size in identifying atrial fibrillation (AF) among hospitalized hypertensives, and to compare its recognition effectiveness with previous scoring systems. Methods We conducted a cross-sectional analysis within hospitalized hypertensives. The discovery, internal and external validation datasets were established. The XGBoost was employed to identify key variables related to AF occurrence, which were ranked based on their importance scores. To gauge the predictive prowess of LAD regarding AF occurrence, we plotted the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). This enabled us to pinpoint the LAD cutoff value corresponding to the maximum Youden index, indicative of susceptibility to AF. Subsequently, Youden index determined the optimal cutoff value from the ROC curve. Delong’s test compared the identification abilities of different tools within the same dataset. Logistic regression analysis assessed the correlation between clinical variables and left atrial size. Results The XGBoost revealed 17 variables affecting AF occurrence in hypertensives, with LAD, age, and HF ranking among the top 3 (Figure 2a). LAD had a more pronounced impact on AF occurrence than other variables. LAD-based identification of AF in hypertensives had AUC of 0.827 (95%CI: 0.816-0.837), with an optimal cutoff of 38mm. Subgrouping the study population by LAD≥38mm, ROC curves showed AUCs of 0.757 (95%CI: 0.745-0.768) for the discovery set, 0.750 (95%CI: 0.731-0.768) for internal validation, and 0.759 (95%CI: 0.743-0.776) for external validation. LAD≥38mm had a more higher and stable AUC value for judging the AF occurrence than CHA2DS2-VASc and C2HEST scores (Figure 2b). Hypertensives with LAD≥38mm had a 9.72-fold higher AF risk than those with LAD&amp;lt;38mm. Conclusion LAD is a pivot determinant for AF occurrence. LAD≥38mm is a valuable identifier for high-risk hypertensives prone to AF.Figure 1.Center illustrationFigure 2.XGboost and Delong’s test of ROC