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BackgroundThe bleeding risk profile of patients with atrial fibrillation (AF) may change over time, and the increment of HAS-BLED score is perceived to result in discontinuations of oral anticoagulants (OACs).ObjectivesTo investigate the changes of HAS-BLED scores of AF patients initially with a low bleeding risk. The associations between continuation or discontinuation of OACs and clinical outcomes after patients’ bleeding risk profile worsened (ie HAS-BLED increased) were studied.MethodsThe present study used Taiwan nationwide health insurance research database. From year 2000 to 2015, a total of 24,990 AF patients aged ≥ 20 years with a CHA2DS2-VASc score  ≥ 1 (males) or  ≥ 2 (females) having an HAS-BLED score of 0–2 who were treated with OACs were identified and followed up for changes of the HAS-BLED scores. Patients who did not refill OACs within 90 days after their HAS-BLED scores increased to  ≥ 3 were defined as discontinuations of OACs. The risks of clinical outcomes were compared between patients who continued or stopped OACs once their HAS-BLED scores increased to  ≥ 3.ResultsMean HAS-BLED score of study population increased from 1.54 to 3.33. At end of 1 year, 5,229 (20.9%) patients had an increment of their HAS-BLED scores to  ≥ 3, mainly due to newly diagnosed hypertension, stroke, bleeding, and concomitant drug therapies. Among 4777 patients who consistently had an HAS-BLED score  ≥ 3, 1,062 (22.2%) stopped their use of OACs. Patients who kept on OACs (n = 3715; 77.8%) even after their HAS-BLED scores increased to ≥ 3 were associated with a lower risk of ischemic stroke (aHR 0.60, 95%CI 0.53–0.69), major bleeding (aHR 0.78, 95%CI 0.67–0.91), all-cause mortality (aHR 0.88, 95%CI 0.79–0.97), and any adverse events (aHR 0.75, 95%CI 0.68–0.82) adjusted for age, sex, heart failure, and HAS-BLED score. These results were consistent among the cohorts after propensity matching.ConclusionsFor patients whose HAS-BLED scores increased to ≥ 3, the continuation of OACs was associated with better clinical outcomes. An increased HAS-BLED score in anticoagulated AF patients may not be the only reason to withhold OACs, but reminds physicians to correct modifiable bleeding risk factors and follow up patients more closely.Associations between Continuation or Discontinuation of Oral Anticoagulants and Risks of Clinical Outcomes after HAS-BLED Scores IncreasedAF atrial fibrillation; aHR adjusted hazard ratio; ICH intra-cranial hemorrhage; OACs oral anticoagulants

Amiodarone is commonly used during therapeutic hypothermia (TH) following cardiac arrest due to ventricular arrhythmias. However, electrophysiological changes and proarrhythmic risk after amiodarone treatment have not yet been explored in TH. Epicardial high-density bi-ventricular mapping was performed in pigs under baseline temperature (BT), TH (32-34°C), and amiodarone treatment during TH. The total activation time (TAT), conduction velocity (CV), local electrogram (LE) duration, and wavefront propagation from pre-specified segments were analyzed during sinus rhythm (SR) or right ventricular (RV) pacing (RVP), along with tissue expression of connexin 43. The vulnerability to ventricular arrhythmias was assessed. Compared to BT, TH increased the global TAT, decreased the CV, and generated heterogeneous electrical substrate during SR and RVP. During TH, the CV reduction and LE duration prolongation were greater in the anterior mid RV than in the other areas, which changed the wavefront propagation in all animals. Compared to TH alone, amiodarone treatment during TH further increased the TAT and LE duration and decreased the CV. Heterogeneous conduction was partially attenuated after amiodarone treatment. After TH and amiodarone treatment, the connexin 43 expression in the anterior mid RV was lower than that in the other areas, compatible with the heterogeneous CV reduction. The animals under TH and amiodarone treatment had a higher incidence of inducible ventricular arrhythmias than those under BT or TH without amiodarone. Electrical heterogeneity during amiodarone treatment and TH was associated with vulnerability to ventricular arrhythmias.

Background Undetected atrial fibrillation (AF) poses a significant risk of stroke and cardiovascular mortality. However, diagnosing AF in real-time can be challenging as the arrhythmia is often not captured instantly. To address this issue, a deep-learning model was developed to diagnose AF even during periods of arrhythmia-free windows. Methods The proposed method introduces a novel approach that integrates clinical data and electrocardiograms (ECGs) using a colorization technique. This technique recolors ECG images based on patients' demographic information while preserving their original characteristics and incorporating color correlations from statistical data features. Our primary objective is to enhance atrial fibrillation (AF) detection by fusing ECG images with demographic data for colorization. To ensure the reliability of our dataset for training, validation, and testing, we rigorously maintained separation to prevent cross-contamination among these sets. We designed a Dual-input Mixed Neural Network (DMNN) that effectively handles different types of inputs, including demographic and image data, leveraging their mixed characteristics to optimize prediction performance. Unlike previous approaches, this method introduces demographic data through color transformation within ECG images, enriching the diversity of features for improved learning outcomes. Results The proposed approach yielded promising results on the independent test set, achieving an impressive AUC of 83.4%. This outperformed the AUC of 75.8% obtained when using only the original signal values as input for the CNN. The evaluation of performance improvement revealed significant enhancements, including a 7.6% increase in AUC, an 11.3% boost in accuracy, a 9.4% improvement in sensitivity, an 11.6% enhancement in specificity, and a substantial 25.1% increase in the F1 score. Notably, AI diagnosis of AF was associated with future cardiovascular mortality. For clinical application, over a median follow-up of 71.6 ± 29.1 months, high-risk AI-predicted AF patients exhibited significantly higher cardiovascular mortality (AF vs. non-AF; 47 [18.7%] vs. 34 [4.8%]) and all-cause mortality (176 [52.9%] vs. 216 [26.3%]) compared to non-AF patients. In the low-risk group, AI-predicted AF patients showed slightly elevated cardiovascular (7 [0.7%] vs. 1 [0.3%]) and all-cause mortality (103 [9.0%] vs. 26 [6.4%]) than AI-predicted non-AF patients during six-year follow-up. These findings underscore the potential clinical utility of the AI model in predicting AF-related outcomes. Conclusions This study introduces an ECG colorization approach to enhance atrial fibrillation (AF) detection using deep learning and demographic data, improving performance compared to ECG-only methods. This method is effective in identifying high-risk and low-risk populations, providing valuable features for future AF research and clinical applications, as well as benefiting ECG-based classification studies.

Abstract Aims To investigate the co-distributions of stroke and bleeding risks in Asian patients with atrial fibrillation (AF) and the clinical benefits of oral anticoagulants (OACs) among AF patients with a single stroke risk factor but at high bleeding risk. Methods and results From 1 January 2001 to 31 December 2016, a total of 404 949 AF patients were retrospectively identified from Taiwan National Health Insurance Research Database. Stroke risk was assessed using the CHA2DS2-VASc score and was categorized into low risk (score = 0 for males and 1 for females), intermediate risk (i.e. a single non-sex stroke risk factor; score = 1 for males and 2 for females), and high risk (score ≥2 for males and ≥3 for females). A high risk of bleeding was defined as a HAS-BLED score ≥3. Around 57.5% of AF patients were at high risk for both stroke and bleeding, and most patients (97.6%) with a low stroke risk were also at low risk for bleeding. Around 18.3% of patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) were at high bleeding risk, and the use of OACs in such patients was associated with a lower risk of composite adverse events of ischaemic stroke, intracranial haemorrhage, or mortality (4.19/100 person-years vs. 5.22/100 person-years, adjusted hazard ratio = 0.781, P = 0.04). Conclusion For AF patients with an intermediate risk of stroke (i.e. a single non-sex stroke risk factor) but at high bleeding risk, the use of OACs was still significantly associated with a better overall clinical outcome.

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. We used the “National Health Insurance Research Database” in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94). In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

Importance Current guidelines recommend the use of non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). Data regarding warfarin sodium use compared with NOAC use in patients with AF with a history of intracranial hemorrhage (ICH) are limited. Objective To compare the clinical outcomes of warfarin use and NOAC use in patients with AF with a history of ICH using a nationwide cohort with AF. Design, Setting, and Participants A nationwide cohort study from January 1, 2012, to December 31, 2016, was performed using data from the Taiwan National Health Insurance Research Database. The dates of analysis were July 1 to September 1, 2019. The study population comprised patients with AF with a history of ICH and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, prior stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease], age 65-74 years, sex category [female]) of at least 1 for men or at least 2 for women who had received warfarin or NOACs. The clinical outcomes were examined using Cox proportional hazards regression analyses among the study population before and after propensity score matching. Exposures Oral anticoagulation with warfarin or NOACs. Main Outcomes and Measures The clinical outcomes measured were all-cause mortality, ischemic stroke, ICH, major bleeding, and adverse events. Results The study cohort included 4540 patients (mean [SD] age, 76.0 [10.5] years; 2653 men [58.4%]), with 1047 patients receiving warfarin (mean [SD] age, 75.1 [11.4] years; 571 men [54.5%]) and 3493 patients receiving NOACs (mean [SD] age, 76.3 [10.2] years; 2082 men [59.6%]). Compared with warfarin use, NOAC use was associated with statistically significantly lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.517; 95% CI, 0.457-0.585), ICH (aHR, 0.556; 95% CI, 0.389-0.796), and major bleeding (aHR, 0.645; 95% CI, 0.525-0.793), whereas the rate of ischemic stroke was similar in the 2 groups (aHR, 0.879; 95% CI, 0.678-1.141). These results were generally consistent after propensity score matching among 973 patients in each group. Conclusions and Relevance Among patients with AF with prior ICH, NOAC use was associated with lower rates of ICH and major bleeding compared with warfarin use, whereas the rate of ischemic stroke was similar in the 2 groups. Among patients with AF with prior ICH, NOACs could be the preferred choice for stroke prevention.

Background Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF. Methods A one-group pretest–posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients’ recognition of SDM, and a 5-point scoring method was used, where “very much” was scored as 5 points, and “totally not” was scored as 1 point. Results Fifty-two patients with AF were enrolled. In terms of patients’ recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of “very much.” The patients’ anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points ( p  < 0.001) to 2.92 (1.3) after SDM. After SDM, the number of patients who decided to take OAC increased from 76.9% to 88.5%, and the 15.4% answering “unclear” decreased to 1.9% ( p  = 0.006). The patients’ anxiety levels after SDM were associated with gender ( p  = 0.025). Conclusions The approach using SDM enhanced our understanding of the pros and cons of OAC treatment and, in patients with AF, decreased anxiety about therapeutic decisions and increased willingness to accept treatment options.

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn’t have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00–0.02; p<0.001), more significant V 4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02–1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V 4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts.

Epicardial fat was closely related to atrial fibrillation (AF). Transthoracic echocardiography (TTE) has been proposed to be a convenient imaging tool in assessing epicardial adipose tissue (EAT). The goal of the present study was to investigate whether the EAT thickness measured on TTE was a useful parameter in predicting procedural outcomes of AF ablations. A total of 227 paroxysmal AF (PAF) and 56 non-paroxysmal AF (non-PAF) patients receiving catheter ablations from 2008-2010 were enrolled. Echocardiography-derived regional EAT thickness from parasternal long-axis view was quantified for each patient. Free of recurrence was defined as the absence of atrial arrhythmias without using antiarrhythmic agents after ablations. The mean EAT thickness of the study population was 6.1 ± 0.8 mm. Non-PAF patients had a thicker EAT than that of PAF patients (7.0 ± 0.7 mm versus 5.9 ± 0.7 mm, p value <0.001). During the follow-up of 16 ± 9 months, there were 95 patients (33.6%) suffering from recurrences of atrial arrhythmias. Non-PAF, chads2 score, left atrial diameter and EAT thickness were independent predictors of recurrence after catheter ablations. At a cutoff value of 6 mm for PAF and 6.9 mm for non-PAF, the measurement of EAT thickness could help us to identify patients at risk of recurrences. EAT thickness may serve as a useful parameter in predicting recurrences after AF ablations. Compared to other imaging modalities, TTE can be an alternative choice with less cost and time in assessing the effects of EAT on ablation outcomes.

Abstract Aims Elderly atrial fibrillation (AF) patients with risk factors of bleeding are often considered ineligible for standard oral anticoagulants (OACs). The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF) trial recently showed that edoxaban 15 mg/day was superior to placebo for preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding. Our aim was to investigate a real-world cohort of AF patients similar to the ELDERCARE-AF cohort, with regard to the impact of direct oral anticoagulant (DOAC) use compared to non-OAC use, in relation to clinical outcomes. Methods and results From 1 January 2012 to 31 December 2016, 15 183 AF patients aged ≥80 years (mean age 86.63 years [SD 4.79]; 48.7% male) with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack (CHADS2) score ≥2 who met the enrolment criteria (generally similar to ELDERCARE-AF) were identified from the Taiwan National Health Insurance Research Database. Patients were categorized into two groups according to their stroke prevention strategies, i.e. without OACs (n = 9084) and DOACs (n = 6099). Patients receiving DOACs were further stratified into reduced-dose- or full-dose-regimen groups. Compared with the non-OAC group as a reference, DOAC use (whether at reduced dose or full dose) was associated with a lower risk of ischaemic stroke (adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.67–0.88) and all-cause mortality (aHR 0.39, 95% CI 0.37–0.42), while the risks of intracranial haemorrhage and major bleeding were similar. The risks of composite outcomes of ‘ischaemic stroke or mortality’ (aHR 0.42, 95% CI 0.40–0.45) and ‘ischaemic stroke or major bleeding or mortality’ (aHR 0.49, 95% CI 0.46–0.52) were significantly lower with DOAC use. When compared with the non-OAC group as the reference group, DOACs (whether reduced dose or full dose) showed a positive net clinical benefit. The results were generally consistent even after propensity matching. Conclusion In routine clinical care, DOACs (whether reduced or full dose) were associated with a lower risk of ischaemic stroke, mortality, and the composite endpoint, when compared with non-OAC use in high-risk elderly AF patients at increased bleeding risk. Our findings provide complementary ‘real-world’ data to support the generalizability of the results of the ELDERCARE-AF trial to other DOACs in daily clinical practice.