Prevention Of Atrial Fibrillation Research Articles

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 >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 <0.0001), had fewer female patients (30.5% vs 39.3%; p <0.0001), and were less likely to be treated with oral anticoagulation (40.5% vs 50.9%; p <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<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.

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

BackgroundPrevious 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.MethodsWe 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.ResultsThe 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.ConclusionOur 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.

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<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<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<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<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

Sex differences in outcomes of percutaneous left atrial appendage closure

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). Percutaneous left atrial appendage closure (LAAC) with the Watchman device has been shown to be noninferior to anticoagulation therapy in clinical trials for stroke prevention in nonrheumatic AF. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in Japan. Since long time ago, sex differences have been attracting attention in the cardiology. Due to the cardiovascular protective effects of endogenous estrogens, premenopausal women are thought to be less likely to develop cardiovascular disease. Whereas, in area of AF, Female with AF have higher stroke risk and female with AF have severe after effect. However, there are few studies on sex differences in LAAC implantation outcomes. Purpose We aimed to identify the sex differences of outcomes of LAAC in Japanese patients. Methods A total of 118 consecutive patients who underwent LAAC at our hospital from January 2020 to August 2023 were prospectively analyzed. Various patient characteristics, comorbidities, and outcomes were identified and compared between male and female. Results Results are shown in Table. Female were older (79 vs. 73 years, p = 0.0009), thinner (Body mass index 22 vs. 24 kg/m2, p = 0.0326), and less likely to have had diabetes (19 vs. 40%, p = 0.0340). Pulmonary embolism was significantly more common in female after LAAC. If anticoagulants are discontinued after LAAC, women’s susceptibility to coagulation may become apparent. Conclusions LAAC was feasible and safe for Japanese patients of both genders. However, these results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic considering sex difference. Especially, we should pay great attention when discontinuing anticoagulants after LAAC in female.

Verification of intra- and inter-atrial conduction during Bachmann's bundle pacing using longitudinal bi-atrial strain

Abstract Introduction Although atrial septal pacing has been reported to reduce atrial fibrillation (AF) burden, there is less evidence regarding its effect on the prevention of permanent AF and the improvement of long-term clinical outcomes. However, Bachmann's bundle pacing (BBp), which features P-wave morphology similar to sinus rhythm and shortened P-wave duration (PWD), was reported to significantly reduce permanent AF recurrences and occurrences compared with right atrial appendage pacing (RAAp) and non-specific right septal pacing. Purpose Possible mechanisms for AF suppression with BBp are that fast inter-atrial conduction through BB decreases global atrial activation time and the dispersion of the overall atrial refractoriness, and it prevents the decrease in left ventricular filling and increase in left atrial pressure associated with delayed left atrial contraction. Intra-and inter-atrial conduction during BBp was evaluated using longitudinal bi-atrial strain. Methods In patients with successful BBp implantation defined by electrocardiographic criteria using SelectSecure pacing lead and C315 delivery catheter (Medtronic, Inc), both left atrium (LA) and right atrium (RA) global longitudinal strain (GLS) in simultaneous phases were measured using Philips Ultrasound Workspace 2D Strain in apical 4-chamber view during atrial pacing to assess intra- and inter-atrial conduction delay. The atrial GLS were measured semi-automatically, and the strain rate was analyzed in the three segments of septal wall, lateral wall, and roof and their average. The negative peak of strain rate during atrial systole was the starting point of atrial contraction, and time to peak (TTP) was measured. The difference in TTP between septal and lateral walls in each atrium was measured as intra-atrial conduction delay and the difference in average TTP between LA and RA as inter-atrial conduction delay. Results Ten patients who underwent successful BBp were enrolled (Sick sinus syndrome: 3, advanced atrioventricular block: 2, complete atrioventricular block: 5). At implantation, bipolar atrial electrogram amplitude was 2.03±0.93 mV, atrial lead impedance was 632.7±157.6 Ω, and atrial pacing threshold was 0.7±0.2 V at 0.4 ms. The PWD during sinus rhythm on the 12-lead ECG was 132.8±10.6 ms, while during BBp it was 108.0±11.9 ms, which was significantly shorter in the BBp group (p<0.001). The intra-atrial conduction delay in RA and LA was 10.9 ± 12.1 ms and 12.1 ± 17.3 ms, respectively, and the inter-atrial conduction delay was 6.6 ± 8.6 ms. On the other hand, for the 10 RAAp and 10 sinus rhythm patients as control groups, the inter-atrial conduction delay was 29.7±13.8 ms and 8.5±9.5 ms, respectively. BBp had significantly less inter-atrial conduction delay than RAAp (p=0.005) and was comparable to sinus rhythm (p=0.719). Conclusion Longitudinal bi-atrial strain suggested that BBp significantly reduced inter-atrial delay and it might be effective in AF suppression.Longitudinal bi-atrial strain

Direct current cardioversion and the impact of short-term exposure to air pollution: a report from the nationwide EP-PARTICLES study

Abstract Background Air pollution and atrial fibrillation (AF) represent significant public health challenges, impacting global health considerably. Numerous studies have focused on areas with high or very high air pollution concentrations, our study examines a unique area in Poland characterized by low to moderate air pollution levels. Our research also addresses a commonly overlooked in research type of pollution - Polish smog. Due to its composition rich in particulate matter and the conditions in which it is formed - is characterized by extremely adverse health effects. Aim To explore the correlation between short-term air pollution exposure and the incidence of acute direct current cardioversion (DCC) for AF treatment. Methods The study area encompassed three voivodeships from Eastern Poland at the NUTS-2 level, with a population of 5,429,378 individuals. Data on hospitalizations from 2011 to 2020 were obtained from the National Health Fund. We combined air pollution and weather condition data from both ground monitoring stations and satellite observations. Emergency visits for AF and DCC were identified using ICD-9 and ICD-10 codes. For a national perspective, we applied meta-analytical strategies to the municipality-specific outcomes. The results are presented as percentage increases in admissions (% IR) with 95% confidence intervals (95%CI). Results Over the decade, 190,454 hospitalizations for AF were reported with a standardized hospitalization rate (SHR) of 358 per 100,000/year (SD=113) and 30,291 DCC admissions (SHR=56.9 [SD]=26). The mean age for AF vs. DCC cohort was 69.6 (SD=11.2) vs. 68.7 (SD=10.4) years, with females representing 56.1% (N=106,822) of AF cases vs. 46.1% (N=13,953) of DCC admissions (P<0.001). Each 10 µg/m3 increase in PM2.5, PM10, and NO2 concentration on the exposure day led to 1.6% (1.1%–2.1%), 1% (0.8%–1.6%), and 1.8% (1.1%–2.6%) increases in acute AF admissions, respectively, with effects lasting up to 6 days. Women and older individuals were more vulnerable to AF episodes induced by air pollution (P<0.001). A 10 µg/m3 increase in PM2.5 on the day of admission increased DCC admissions by 1.5% (0.1%–2.9%, P=0.04), with effects persisting for up to 3 days. The impact of PM10 was time-delayed: 1.3% (0.2%–2.4%, P=0.02) for LAG1 (i.e. one day after exposure), and 1.1% (0.1%–2.2%, P=0.4) for LAG2. No significant effects of gaseous pollutants on DCC (SO2, NO2, and BaP) were observed, nor any differences in the effects by age or sex. Exposure-response functions show steeper slopes of the PM2.5 associations in the lower ranges of exposures, far below air quality norms set by the World Health Organization. Conclusions Air pollution acts as a triggering factor for acute AF hospitalizations and DCC. The differential impact of air pollution on AF events between groups highlights that women and older individuals are particularly vulnerable. Air pollution exposure should be considered into AF management and prevention strategies.Pooled exposure–response function: % inc

Factor XI/XIa Inhibitors: What We Now Know

The emerging class of agents targeting factor XI/XIa offers the paradigm-shifting possibility of ‘haemostasis-sparing anticoagulation’: protection from stroke and other thromboembolic events with a benign bleeding profile. With three investigational agents now into late-phase development, two presentations delivered at the European Society of Cardiology (ESC) Congress 2024, held in London, UK, have added to our knowledge of this innovative and diverse class. The first of these presentations shared the full data from the OCEANIC-AF Phase III trial, in which the small molecule factor XIa inhibitor asundexian was compared with the factor Xa inhibitor apixaban for stroke prevention in atrial fibrillation, and reviewed the probable reasons for the failure of this trial to meet its efficacy endpoint. The second presentation was a secondary analysis from the AZALEA-TIMI 71 Phase II trial, in which the safety of the monoclonal antibody factor XI inhibitor abelacimab was compared with that of the factor Xa inhibitor rivaroxaban in patients with atrial fibrillation undergoing invasive procedures. This article is based on a post-ESC interview with Jeffrey I. Weitz, Professor of Medicine and Biochemistry and Biomedical Sciences at McMaster University, Canada; Canada Research Chair (Tier 1) in Thrombosis and the Heart and Stroke Foundation; J.F. Mustard Chair in Cardiovascular Research; Executive Director of the Thrombosis and Atherosclerosis Research Institute (TaARI), in Hamilton, Canada; and Secretary General of the International Society on Thrombosis and Haemostasis (ISTH). It assesses the current status and future prospects of the factor XI/XIa inhibitor class in light of these recent developments.

L-Carnitine: A New Therapeutic Option for the Prevention of Atrial Fibrillation in Non-Cardiac Surgery-A Single-Group Interventional Pilot Study.

Background: L-carnitine is essential in lipid metabolism and reportedly has preventive effects for arrhythmia. Our objective was to examine the incidence of postoperative atrial fibrillation (POAF) and changes in serum biomarker levels following perioperative L-carnitine administration in patients with lung cancer. Methods: Thirteen patients undergoing a lobectomy with preoperative serum brain natriuretic peptide levels >24 pg/mL were perioperatively administered L-carnitine for 5 days (3 g/3×). Accurate 95% confidence intervals (CI) for POAF incidence were calculated. Serum biomarkers for POAF in lung cancer and target proteins for L-carnitine were evaluated by using open-source data from proteomic analysis. Results: The incidence of POAF was 38.5% (95% CI 13.9%-68.4%). Fatty acid-binding protein 4 (FABP4) was selected as a candidate biomarker from 1472, 63, and 26 proteins related to lung cancer, L-carnitine, and AF, respectively. A positive correlation was observed between the predicted POAF incidence rate and preoperative FABP4 levels (Pearson's r = 0.5183). The mean change in serum FABP4 after L-carnitine administration for 5 days was -2.9 ng/mL (95% CI -4.9 to -0.89 ng/mL). Conclusions: The incidence of POAF after a lobectomy was 38.5% after the perioperative administration of L-carnitine for patients at a high risk of POAF. The serum FABP4 level demonstrates potential as a candidate biomarker for POAF prediction.

Mineralocorticoid receptor antagonists for atrial fibrillation prevention: effective solution or empty promise?

Mineralocorticoid receptor antagonists for atrial fibrillation prevention: effective solution or empty promise?

Trends over time in oral anticoagulation and stroke rates in atrial fibrillation: A community-based study

ObjectivesOver the last decade, direct oral anticoagulants (DOAC) have become preferred over warfarin for stroke prevention in atrial fibrillation (AF). The objectives of this study were to quantify the shift over time from warfarin to DOACs and parallel changes in ischemic and hemorrhagic stroke rates in AF. Materials and methodsThis community-based retrospective study was undertaken within a single integrated health care network from 2011 to 2021. Changes over time in warfarin and DOAC use were quantified by year, both overall and stratified by CHA2DS2-VASc score. Ischemic and hemorrhagic stroke rate changes over time were evaluated by Poisson regression. Stroke rates were evaluated in different time eras: 2011–2015 and 2016–2021. ResultsAmong 31,978 AF patients followed an average of 5.5 years, any OAC use increased from 50.2 % (2011) to 59.4 % (2020) (p < 0.001). Warfarin use decreased from 49.3 % to 30.8 %, while DOAC use increased from 2.0 % to 30.8 % (both p < 0.001). In 2020, patients with CHA2DS2-VASc 0–1 and 2–5 were more likely to use DOACs than warfarin (18.6 % vs. 6.7 %; 33.0 % vs. 28.2 %), whereas in CHA2DS2-VASc 6–9 DOACs were used less frequently (30.0 % vs. 40.8 %). Ischemic stroke rates significantly increased by 19 % (95 % CI: 7 %, 32 %) from 2011 to 2015, but significantly decreased by 18 % (10 %, 26 %) from 2016 to 2021. Hemorrhagic stroke rates stabilized in 2016–2021 (+3 %; −18 %, 30 %) after increasing in 2011–2015 (+36 %; 4 %, 78 %). ConclusionImprovements in ischemic and hemorrhagic stroke rates coincided temporally with increased uptake of OACs and a shift toward increased uptake of DOACs relative to warfarin.

The Predictive Value of T-Lymphocyte Subset Distribution for the Occurrence and Prognosis of Atrial Fibrillation

Introduction: The effect of T lymphocytes on atrial fibrillation (AF) is still unclear. We aimed to assess the associations between the T-lymphocyte subgroup distribution and incident AF and AF prognosis. Methods: Consecutive patients were enrolled from June 2020 to October 2021. Their T-cell subgroups, including CD3, CD4, and CD8 T cells, and the CD4/CD8 ratio (CDR) were measured. We assessed the relationships between the CDR and composite endpoints, including hospitalization due to heart failure, stroke or systemic embolism, and cardiovascular mortality rates. Results: A total of 45,905 patients, among whom 818 had AF, were enrolled. The proportions of the T-lymphocyte subgroups CD3 (OR: 0.9995; 95% CI: 0.9993–0.9997, p < 0.001), CD4 (OR: 0.9995; 95% CI: 0.9991–0.9998, p = 0.004), and CD8 (OR: 0.9988; 95% CI: 0.9984–0.9992, p < 0.001) and the CDR (OR: 1.2714; 95% CI: 1.1355–1.4165, p < 0.001) were correlated with AF incidence. The CDR was associated with AF incidence (OR: 1.1998; 95% CI: 1.0746–1.3336, p < 0.001) after adjustment. High CDR was associated with a higher rate of hospitalization due to heart failure (HR: 3.45; 95% CI: 1.71–6.96, p < 0.001), stroke, or systemic embolism (HR: 2.54; 95% CI: 1.32–4.91, p = 0.005), and cardiovascular mortality (HR: 2.25; 95% CI: 1.05–4.84, p = 0.038). There was no significant difference in all-cause mortality between CDR strata (HR: 1.61; 95% CI: 0.90–2.87, p = 0.111). Conclusion: Elevated CDR was positively associated with the incidence and prognosis of AF. This finding may help improve the prevention and treatment of AF.

Clinical outcomes of Asian patients with newly diagnosed atrial fibrillation and previously diagnosed atrial fibrillation: Insights from the CODE-AF registry

BackgroundAtrial fibrillation (AF) may have different clinical features in its early phase. Objective: This study compared the characteristics and clinical outcomes of early-phase AF with later-phase AF using a large multicenter prospective registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF]). MethodsPatients enrolled between June 2016 and March 2021 were divided into two groups based on AF duration: (1) newly diagnosed (AF duration ≤90 days) and (2) previously diagnosed (AF duration >90 days). The baseline characteristics and clinical outcomes were compared. ResultsAmong the 10,001 study participants (mean age 67.0±14.5 years, and 64% men), 22% were defined as newly diagnosed and 78% as previously diagnosed. Newly diagnosed patients had fewer comorbidities and more unhealthy social behaviors. Despite lower prescription rates of oral anticoagulant, direct oral anticoagulants were more frequently used. The newly diagnosed group also had a higher composite clinical outcome risk within 90 days (adjusted HR 1.81, 95% CI 1.30–2.53, P<0.001) and revealed a higher risk of all bleeding and heart failure admission within 90 days. No significant differences remained between the groups over a 36-month follow-up. ConclusionsPatients with early-stage AF were younger and had fewer comorbidities. While there was a higher risk of heart failure admissions and minor bleeding, the risk of death, stroke, and major bleeding was not significantly increased. Structured monitoring and management during the initial months are essential to address these risks.