CHA2DS2-VASc Research Articles

Refining the CHA2DS2VASc risk stratification scheme: Shall we drop the Sex Category criterion?

Abstract Background The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years. Objective To assess the impact of removing the sex category (Sc) from the CHA2DS2VASc score, thus validating a non-sex CHA2DS2VASc (i.e., CHA2DS2VA) score. Methods We analysed UK primary and secondary care data comprising 195,719 patients with AF followed between 1998-2016 (mean age: 75.9±12.3 years; 49.2% women). Among 126,428 non-anticoagulated patients, we compared the CHA2DS2VASc vs. CHA2DS2VA scores every calendar year. Results Throughout 413,007 patient-years, a total of 8,742 events of ischaemic stroke or systemic embolism were recorded. Sex differences in thromboembolic risk were not observed in the lower-risk population, but higher stroke rates were consistently seen in female patients in the higher-risk category (i.e., CHA2DS2VA ≥2). C-statistics for both CHA2DS2VA and CHA2DS2VASc scores were similar over the years (ranging from 0.62 to 0.71). With CHA2DS2VA no relevant differences were observed in IDI, and NRI resulted in improved reclassification (11%) in lower thromboembolic risk groups. NRI suggested misclassification in higher thromboembolic risk patients (-7%), but this did not affect their indication for anticoagulation (i.e., patients retained their high-risk status). Conclusions Removing Sc from the CHA2DS2VASc score does not affect its ability to discriminate thromboembolic events in the AF population. Use of CHA2DS2VA may simplify initial decision-making for thromboprophylaxis.

An evaluation of the impact of the Lambeth PCN pharmacist anticoagulation skills development project

Abstract Background Atrial Fibrillation (AF) is a prevalent heart condition linked to significant morbidity and mortality due to its association with stroke.1 Despite the clear benefits of anticoagulation in reducing stroke risk, its underuse and suboptimal monitoring remain a concern.2 Aim This study aims to evaluate the impact of a pharmacist-led training programme in Lambeth, London, focusing on improving pharmacists' competency and confidence in managing Direct Oral Anticoagulants (DOACs). It assesses if the training met pharmacists' needs, evaluates current monitoring patterns to determine if training was warranted, and identified areas for further training improvement. Methods The study involved 41 GP practices across 9 Primary Care Networks (PCNs) in Lambeth. Practices were eligible based on their involvement in the management of AF patients prescribed DOACs. All pharmacists at these practices who were actively engaged in anticoagulation management and willing to participate in pre- and post-training assessments were invited to take part. Recruitment involved direct communication through practice managers and emails detailing the study’s objectives and benefits. DOAC monitoring data was extracted from patient medication records and subsequently compared to the South East London anticoagulation guidelines3 to establish compliance percentages. A competency assessment was conducted on pharmacists using a pre- and post-training checklist framework devised by the Consultant Anticoagulant Team at Guy’s and St Thomas’ NHS Foundation Trust (GSTT). The Wilcoxon signed-rank test analysed this paired data, with a p < 0.05 set for statistical significance. Additionally, semi-structured interviews were conducted to gather insights on their training experience and perceptions. Transcripts were coded using NVIVO software to identify themes. Ethical approval was obtained from Kingston University London. Results Of the 2,987 AF patients across the 41 GP practices, 87.6% were on DOACs. Prescribing and monitoring trends were consistent across all GPs, with scope to improve compliance across all parameters, such as CHA₂DS₂-VASc score assessment prior to DOAC initiation. The competency assessment, completed by ten pharmacists, showed a significant improvement post-training, with mean scores rising from 3.3 to 4.1 (p< 0.00001). Improvements were seen across all domains, particularly in explaining the rationale for anticoagulation, showing CHA₂DS₂-VASc and HASBLED scores, and discussing modifiable HASBLED factors. Competency in patient communication remained highest, while managing particular cases like reversal procedures and patients with cancer showed lower competency, indicating areas for training improvement. The interviews, conducted with ten pharmacists, revealed three main themes: (1) Confidence and competence in anticoagulant prescribing and optimisation, (2) Evaluation of the training programme's effectiveness, and (3) Professional growth and career development. Pharmacists reported greater confidence in managing DOACs post-training, though challenges remained in patient engagement and collaboration with GPs lacking DOAC knowledge. Discussion / Conclusion The evaluation proved a positive impact on pharmacists' competency and confidence in DOAC management. Suboptimal monitoring practices in Lambeth highlighted the need for this training programme and its crucial role in improving patient outcomes. Limitations include a small interview sample and potential biases in self-reported evaluations. A longitudinal study is recommended to assess long-term impacts. Ongoing training and systematic data collection are essential, and similar training should be extended to other healthcare professionals.

Machine learning for outcome prediction in patients with non-valvular atrial fibrillation from the GLORIA-AF registry

Clinical risk scores that predict outcomes in patients with atrial fibrillation (AF) have modest predictive value. Machine learning (ML) may achieve greater results when predicting adverse outcomes in patients with recently diagnosed AF. Several ML models were tested and compared with current clinical risk scores on a cohort of 26,183 patients (mean age 70.13 (standard deviation 10.13); 44.8% female) with non-valvular AF. Inputted into the ML models were 23 demographic variables alongside comorbidities and current treatments. For one-year stroke prediction, ML achieved an area under the curve (AUC) of 0.653 (95% confidence interval 0.576–0.730), compared to the CHADS2 and CHA2DS2-VASc scores performance of 0.587 (95% CI 0.559–0.615) and 0.535 (95% CI 0.521–0.550), respectively. Using ML for one-year major bleed prediction increased the AUC from 0.537 (95% CI 0.518–0.557) generated by the HAS-BLED score to 0.677 (95% CI 0.619–0.724). ML was able to predict one-year and three-year all-cause mortality with an AUC of 0.734 (95% CI 0.696–0.771) and 0.742 (95% CI 0.718–0.766). In this study a significant improvement in performance was observed when transitioning from clinical risk scores to machine learning-based approaches across all applications tested. Obtaining precise prediction tools is desirable for increased interventions to reduce event rates.Trial Registryhttps://www.clinicaltrials.gov; Unique identifier: NCT01468701, NCT01671007, NCT01937377.

Artificial intelligence-based prediction of neurocardiovascular risk score from retinal swept-source optical coherence tomography–angiography

The recent rise of artificial intelligence represents a revolutionary way of improving current medical practices, including cardiovascular (CV) assessment scores. Retinal vascular alterations may reflect systemic processes such as the presence of CV risk factors. The value of swept-source retinal optical coherence tomography–angiography (SS OCT-A) imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features. We report on the interest of using machine-learning (ML) and deep-learning (DL) models for CV assessment from SS OCT-A microvasculature imaging. We assessed the accuracy of ML and DL algorithms in predicting the CHA2DS2-VASc neurocardiovascular score based on SS OCT-A retinal images of patients from the open-source RASTA dataset. The ML and DL models were trained on data from 491 patients. The ML models tested here achieved good performance with area under the curve (AUC) values ranging from 0.71 to 0.96. According to a classification into two neurocardiovascular risk groups, the EfficientNetV2-B3, a well suited DL model for retinal OCT-A images, predicted risk correctly in 68% of cases, with a mean absolute error (MAE) of approximately 0.697. Our models enable a confident prediction of the CHA2DS2-VASc score from SS OCT-A imaging, which could be a useful tool contributing to the assessment of neurocardiovascular profiles in the future.

Atrial Fibrillation in Patients with Very High Risk for Stroke and Adverse Events—Insights from the Observational ARENA Study

Background: Atrial fibrillation (AF) is a major cause of stroke. An individual risk estimation remains challenging, as AF patients with and without cerebrovascular event (CVE) may differ in yet unknown factors beyond those covered by the CHA2DS2-VASc score. We aimed to identify differences between AF patients with and without CVE with regard to AF characteristics and treatment, vascular risk factors and comorbidities, prognosis and outcome. Methods: We analyzed patients included in the Atrial Fibrillation Rhine-Neckar Region (ARENA) Project, an observational cohort study of patients with AF. Patients were recruited by their general practitioner or during a hospital stay and were divided into two groups for the present analysis: patients with acute CVE at baseline and/or history of CVE versus patients without CVE. Follow-up at 1 year was conducted via phone call. Results: Of 2061 included patients (60.6% male), 292 (14.2%) belonged to the CVE group. Patients in the CVE group were older (mean age 74.6 versus 71.7 years; p < 0.001) and had a higher CHA2DS2-VASc score at baseline (5.3 versus 3.3 points; p < 0.001) based on the preceding CVE. Moreover, patients with either acute or chronic CVE had a larger left atrium (median diameter 47/46 mm versus 44 mm; p = 0.001). Patients with acute CVE had structural heart diseases (p < 0.001) less frequently than patients with previous or without CVE. Mortality at 1 year (HR 1.95; 95%-CI 1.37–2.78) was more frequent in the CVE group (p < 0.001). During 1-year of follow-up, stroke occurred more frequently in survivors with CVE (2.9% versus 0%; p < 0.001). Conclusions: AF patients with CVE have a significantly worse prognosis than AF patients without CVE. Atrial structural remodeling, underlying cardiovascular disease, stroke-induced heart injury and further unidentified factors may account for this finding. Characterization of AF patients including echocardiography to detect atrial structural remodeling may be helpful in risk stratification beyond classical scores.

Pulsed Field Ablation in Atrial Fibrillation: Initial Experience of the Efficacy and Safety in Pulmonary Vein Isolation and Beyond

Regional differences in pulsed field ablation (PFA) adoption for pulmonary vein isolation (PVI) with additional posterior wall ablation (PWA) in Asia remains unknown. We hereby report our experience on the safety and efficacy of PFA in AF ablation. Consecutive AF patients who underwent PFA from September 2022 to January 2024 were included. The primary efficacy endpoint was freedom from atrial arrhythmia recurrence after a 90-day blanking period at 12 months. Safety endpoints included 30 days of all-cause death, cardiac tamponade, stroke, myocardial infarction, and heart failure hospitalization. One hundred and one (72.3% males, 79.2% pAF) patients underwent PFA for AF. Thirty-one (30.7%) had structural heart disease with mean LVEF of 57.4 ± 8.1% and CHA2DS2-VASc score of 1.4 ± 1.3. Twenty-nine (28.7%) underwent additional PWA (PVI + PWA) using PFA. PWA was acutely successful in all patients. Patients who underwent PWA were more likely to have persistent AF and require general anesthesia and electroanatomic mapping (all p < 0.05). Total PFA applications for PVI, LA dwell time, procedural time, and fluoroscopy time were similar between the PVI-only and PVI + PWA groups (all p > 0.05). The 1-year atrial arrhythmia recurrence rates were 10% for pAF and 21% for the persistent AF group. The primary efficacy endpoint was not significantly different between the PVI-only and PVI+PWA groups (12-month KM estimates 90.3% [95% CI, 83.3–97.3] and 82.8% [95% CI, 68.1–97.4], respectively). There were no complications related to PFA use. PFA can be safely, effectively, and efficiently adopted for AF ablation. Additional PWA, if pursued, had similar procedural metrics to the PVI-only strategy without increased complications.

The ETNA-AF Europe registry: 4-year data of edoxaban use in atrial fibrillation in the Italian real world compared to the European cohort

The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years. Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population. In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding. These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Left Atrial Appendage Closure in Atrial Fibrillation Patients with Cancer

Background: There are limited data about left atrial appendage closure (LAAC) in patients with cancer. We therefore sought to compare the outcome after LAAC in patients with vs. without cancer in a multicentre registry. Methods: In this sub-analysis of the prospective Austrian LAAC Registry, we analysed consecutive patients undergoing LAAC to assess the relationship between baseline characteristics and outcome in patients with vs. without cancer. Inverse probability weighting was performed to adjust for differences in baseline characteristics. Results: A total of 486 consecutive patients from 9 centres with a median age of 75 years (IQR 70–79 years; 35.8% female) were included. Fifty-seven patients (11.7%) had a history of cancer. The median CHA2DS2-VASc and HAS-BLED scores were similar in both groups (median [IQR], 4 [4–6] vs. 5 [3–5], p = 0.415; 4 [3–4] vs. 3 [3–4], p = 0.428 in cancer vs. other patients). Cancer patients were significantly older, and anaemia and gastrointestinal bleeding were significantly more common. Major procedural complications occurred in 5.3% vs. 7.0% (p = 0.276) of patients. The cumulative five-year survival rates were 80.7% and 84.8% in cancer vs. other patients (adjusted hazard ratio for death 1.29 [95% CI 0.67–2.48], p = 0.443). There were also no differences in one-year survival (96.1% vs. 94.0%, p = 0.582) and five-year event-free survival (64.9% vs. 74.4%, p = 0.124). Conclusions: In daily clinical practice, LAAC has already been accepted as a treatment option in patients with cancer. This retrospective analysis shows that short-term and adjusted long-term complications are similar in patients with vs. without cancer undergoing LAAC.

Clinical impact of combined assessment of the CHADS2 score and geriatric nutritional risk index on clinical outcomes in patients with lower extremity artery disease without atrial fibrillation

Abstract Background The CHADS2 score is a well-known risk score for ischemic stroke in atrial fibrillation (AF) patients. Recently, it has been reported that the CHADS2 score was associated with an increased risk of new-onset lower extremity artery disease (LEAD) in patients without AF, the association between the CHADS2 score and clinical outcomes in patients with LEAD undergoing endovascular treatment (EVT) without AF remains unclear. Furthermore, malnutrition assessed by the geriatric nutritional risk index (GNRI) has been reported to be predictive of clinical outcomes in patients with LEAD. However, there are limited studies regarding the association of combined assessment of the GNRI and CHADS2 score and clinical outcomes in patients with LEAD without AF. Purpose The purpose of this study was to investigate the association between the combined assessment of GNRI and CHADS2 score, and mortality of LEAD patients undergoing EVT without AF. Methods This retrospective study investigated 236 consecutive LEAD patients who underwent EVT without AF. CHADS2 scores were calculated by assigning one point for heart failure, hypertension, age ≥75 years, and diabetes; and assigning 2 points for a prior history of stroke or transient ischemic attack. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)], and the CHADS2 score and GNRI were calculated for each patient. We scored GNRI by assigning 2 points to low GNRI (GNRI &amp;lt;82) and 1 point to intermediate GNRI (GNRI =82 to &amp;lt;92). We then calculated the CHADS2 plus GNRI score for each patient and then patients were divided into the high CHADS2 plus GNRI scoregroup (CHADS2 plus GNRI score&amp;gt; 2, n = 123) and the low CHADS2plus GNRI score group (CHADS2 plus GNRI score≤ 2, n = 113) according to the median CHADS2 plus GNRI score. We investigated the associations between all-cause mortality in patients with LEAD who underwent EVT and the CHADS2 plus GNRI score. Results The mean age was 71.9±10.4 years, and 66.9% were men. During the median follow-up of 752 (283–1472) days, 50 patients died. Kaplan-Meier curves revealed that the cumulative incidence of all-cause death was significantly higher in the high CHADS2 plus GNRI score group than in the low CHADS2 plus GNRI score group (log-rank p = 0.003). Furthermore, even in the multivariate analysis,after adjusting for other risk factors including hemodialysis and clinical frailty scale, CHADS2 plus GNRI score was independently associated with all-cause death (per one score increase, hazard ratio: 1.26, 95% confidence interval (CI) 1.01-1.56, P=0.038). Conclusions In LEAD patients who underwent EVT without AF, a higher CHADS2 plus GNRI score was associated with an increased risk of all-cause death. A Combined CHADS2 plus GNRI score assessment may be a useful prognostic marker in patients with LEAD without AF.

A cohort study examining predictors of stroke and bleeding among people with congenital heart disease and atrial fibrillation

Abstract Background Congenital Heart Disease (CHD) is associated with development of atrial fibrillation (AF) at an early age. With increased survival of this cohort into adulthood, the prevalence of concurrent CHD and AF is expected to increase over the next several decades. Little is known about the utility of clinical risk factors or prediction models in determining bleeding or stroke rates in adults with CHD and AF. Purpose This study aims to measure the performance of the CHADSVASC and HASBLED scores in a cohort of people with CHD. The association between traditional stroke and bleeding risk factors, as well as CHD-specific factors, will be quantified. Methods Patients age 18 or older attending one of three centers in the USA were included in this study if they had a history of AF on ECG, holter monitor or device interrogation, in addition to a diagnosis of Tetralogy of Fallot (TOF), Double Outlet Right Ventricle (DORV), or Pulmonary Atresia with Intact Ventricular Septum (PA-IVS). Outcomes were major bleeding event, and stroke rate. Analysis was conducted using cox univariable regression controlling for current age. Receiver operator curve and c-statistics were produced for the CHADSVASC and HASBLED scores respectively. Results 326 people were included in this study, of whom 161 (49.5%) had TOF secondary to Pulmonic Stenosis, 126 (38.8%) had TOF secondary to Pulmonary Atresia, 25 (7.7%) had DORV, and 155 (47.7%) had PA-IVS. 227 people used warfarin (79.4%), 28 (9.8%) used apixaban, 9 (3.1%) used Rivaroxaban, 3 (1%) used Edoxaban, and 5 (1.7%) used Enoxaparin for a period of at least 30 days during the study. 13 (4.5%) people didn’t receive anticoagulation during the study. 26 people had a stroke (8.8%) while 85 people (28.6%) had a major bleeding event. Only the CHADSVASC score was significantly associated with stroke rates (HR 2.103, 95% CI 1.555 to 2.844, p&amp;lt;0.001). Clinical variables, such as subtype of CHD, prior conduit placement or unifocalization were not associated with stroke or major bleeding events. C-statistic for the CHADSVASC score in predicting stroke events was 0.755 (Figure 1). C-statistic for the HASBLED score in predicting major bleeding was 0.442 (Figure 2). Conclusions Among people with CHD and AF, the CHADSVASC score can robustly predict stroke events. Other clinical variables are less valuable in predicting either bleeding or strokes. The HASBLED score likely doesn’t have a role in predicting major bleeding episodes in this cohort.

Assessing stroke and mortality risk in heart failure: the CHA2DS2-VASc score's prognostic value in patients with and without atrial fibrillation - a systematic review and meta analysis

Abstract Background Heart failure (HF) is a common cardiovascular disorder that is linked to substantial morbidity and mortality. The CHA2DS2-VASc score, originally designed to assess the risk of stroke in patients with atrial fibrillation, has demonstrated potential as a prognostic indicator for adverse outcomes in patients with heart failure. This systematic review and meta-analysis aimed to assess the predictive accuracy of the CHA2DS2-VASc score in determining the occurrence of stroke and increased mortality rates in patients with heart failure. Methods A thorough search of electronic databases, such as PubMed, EMBASE, and the Cochrane Library, was performed to find pertinent papers published until the search cutoff date. Included studies examined the correlation between the CHA2DS2-VASc score and the likelihood of stroke or death in patients with heart failure. The assessment of the quality of the included studies was conducted using recognized criteria, and data were collected for quantitative synthesis. Findings The meta-analysis encompassed four studies (45864 patients), revealing a consistent and substantial correlation between elevated CHA2DS2-VASc scores and heightened risks of both stroke and mortality in heart failure patients. More precisely, patients with CHA2DS2-VASc scores ≥4 had a greater risk of stroke compared to those with scores &amp;lt;4 (odds ratio 0.38, 95% confidence interval 0.33-0.43, p-value &amp;lt; 0.00001). The combined data showed homogeneity (p-value = 0.24, I2 = 29%). Similarly, patients with CHA2DS2-VASc scores ≥4 had a higher risk of mortality compared to those with scores &amp;lt;4 (OR 0.49, 95% CI 0.30-0.80, P = 0.05). However, the combined data showed significant heterogeneity (P &amp;lt; 0.00001, I2 = 96%). Conclusion The CHA2DS2-VASc score is a useful predictive tool for identifying heart failure patients who are hospitalized and at a high risk of both stroke and high mortality. The results of this study provide evidence for the practicality of using the CHA2DS2-VASc score for risk stratification in patients with heart failure. Additional investigation is necessary to confirm these findings and examine the incorporation of the CHA2DS2-VASc score into risk assessment algorithms for tailored patient management.Figure:Risk of strokeFigure:Risk of mortality

Association between CHA2DS2-VASc score and left atrial function by speckle tracking echocardiography in patients with sinus rhythm

Abstract Background The CHA2DS2-VASc score is a scoring system that was first used for the risk assessment of cerebrovascular or thromboembolic events in patients with atrial fibrillation (AF). The factors that constitute the CHA2DS2-VASc scoring system can all individually have an impact on LA function. The application of this scoring system can also be applied to patients without AF. The LA structural remodeling and/or functional impairment play a part in the pathogenesis and development of AF and independent of rhythm, may result in atrial hemostasis and confer a prothrombotic diathesis, resulting in thromboembolic stroke. Speckle- tracking echocardiography (STE) makes it possible to measure LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement. Purpose The aim of our study was to assess the left atrial function in patients with sinus rhythm with different CHA2DS2-VASc scores (low, moderate and high) by speckle tracking echocardiography and to identify the association between them. Methods This study was conducted using prospectively collected data (1st May, 2022 to 30th October 2022) from patients with sinus rhythm and different CHA2DS2-VASc scores (50 Low risk score patients (1 for females and 0 for males), 50 moderate risk score patients (2 for females and 1 for males) and 50 high risk score patients (≥3 for females and ≥2 for males) After obtaining an informed consent, all volunteers underwent thorough history taking, 12 lead ECG and conventional transthoracic echocardiography and speckle-tracking echocardiography. Results LA strain during the reservoir (LASr) and conduit phases (LAScd) were statistically significantly lower in the high-risk score group (33.2 ± 7.1 and 20.3 ± 5.7) than the moderate-risk score group (36.9 ± 6.1 and 23.5 ± 4.8, p = 0.005 and 0.003 respectively) and low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9, p &amp;lt; 0.001). In addition, LASr and LAScd were statistically significantly lower in moderate- risk score group (36.9 ± 6.1 and 23.5 ± 4.8) than the low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9 ,p=0.007 and 0.001 respectively). Conclusion Higher CHA2DS2-VASc scores were associated with decreased LA strain during the reservoir and conduit phases as markers of LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement.

Resumption of anticoagulation therapy among Non-Valvular Atrial Fibrillation (NVAF) patients with prior intracranial haemorrhage

Abstract Purpose Resumption of anticoagulation therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF) suffering from intracranial haemorrhage (ICH) is challenging in clinical practice. The aim of this study was to evaluate impact of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription obtained from electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Risks of ischemic stroke, recurrent ICH and all-cause mortality were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC and HASBLED scores. Sub-analysis was conducted to compare outcomes between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference among patients who resumed DOAC or VKA. Results Of 982 patients who met inclusion criteria (mean age 77.7±10.9, female 40.9%), 39.1% (n=384) were OAC naive, 32.2% (n=316) resumed DOAC, 12.6% (n=124) resumed VKA, 9.0% (n=88) discontinued DOAC and 7.1% (n=70) discontinued VKA. During a median follow-up period of 2.0 (IQR: 0.7-3.5) years, no statistically significant difference in risk of ischemic stroke was observed among 5 groups. Discontinuation of DOAC was associated with markedly higher risk of ischemic stroke (aSHR=8.32 (1.8-39.3)) only among AF patients with CHA2DS2VASC score ≥ 4, Risk of recurrent ICH was higher in patients who resumed VKA (aSHR=1.6(1.0-2.5)). Sub-analysis demonstrated resumption of apixaban was associated with lowest risk of recurrent ICH (aSHR=0.6(0.4-0.9)). Compared to OAC naïve patients, those who resumed DOAC (aSHR=0.5(0.4-0.7)) had lowest risk of all-cause mortality, whereas discontinuation DOAC (aSHR=1.9(0.4-2.5) and VKA (aSHR=1.6(0.2-2.2)) were both associated with increased mortality. Conclusion Our real-world data revealed among NVAF patients with prior ICH long term discontinuation of OAC was associated with increased risk of ischemic stroke. Recurrent ICH was highest among patients who resumed VKA and lowest with apixaban.

The long-term usage of statin prevents adverse events in patients with atrial fibrillation

Abstract Background The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Purpose Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF. Methods This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined. Results We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p &amp;lt; 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p &amp;lt; 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p &amp;lt; 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories. Conclusions Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.

Predictors of new-onset in-hospital atrial fibrillation in 122 089 patients admitted with COVID-19: an Australian statewide population study

Abstract Background New-onset atrial fibrillation (AF) when encountered in COVID-19 patients may be associated with increased mortality and thromboembolic events. Few studies have investigated predictors of new-onset AF in the context of COVID-19 and no study has assessed the utility of CHA2DS2VASc score in predicting new-onset AF in COVID-19 patients. Purpose This study aims to identify independent predictors of new-onset in-hospital AF in patients admitted with COVID-19. Methods Patients admitted with COVID-19 (1-Jan-2020 to 30-Sept-2021) were identified from the Admitted-Patient-Data-Collection database in an Australian state, stratified by AF status (no-AF vs new-AF during index COVID-19 admission) and followed-up until 31-Mar-2022. Patients with prior-AF were excluded from analysis. New-AF was defined as new-onset AF during the hospital admission for COVID-19. Independent predictors of new-AF were identified using multivariable logistic regression. Receiver Operating Characteristic (ROC) derived Area Under Curve (AUC) score was performed to determine the predictive power of independent predictors of new-AF. Results The cohort comprised 122089 COVID-19 patients (median age 62.7 yrs; 48.5% males) of whom 5140 developed new-AF (4.2%). Compared to patients with no-AF, patients with new-AF had a higher prevalence of comorbidities and cardiac risk factors (hypertension, diabetes and smoking) as well as a higher CHA2DS2VASc score (p &amp;lt; 0.001) (Table 1). Independent predictors of new-AF included referral from Emergency Department (adjusted odds ratio [aOR] =1.63, 95% confidence interval [CI]=1.49-1.78, intensive-care-unit admission (aOR=3.46, 95%CI=3.22-3.71), current/ex-smoker (aOR=1.20, 95%CI=1.12-1.27), prior coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) (aOR=1.33, 95%CI=1.01-1.75), valvular heart disease (aOR=3.20, 95%CI=2.73-3.75), malignancy (aOR=1.15, 95%CI=1.02-1.29), chronic pulmonary disease (aOR=1.30, 95%CI=1.19-1.42) and higher CHA2DS2VASc score (per-1-score increase: aOR=1.62, 95%CI=1.59-1.65) (all P&amp;lt;0.05). CHA2DS2VASc score alone had an AUC score of 0.729 (95%CI=0.72-0.74) (Figure 1). Adding the above additional independent variables to CHA2DS2VASc score improved the predictive model to an overall AUC score of 0.773 (95%CI=0.77-0.78), p &amp;lt; 0.001. Conclusions This study identified patients at risk of developing new-AF in the setting of COVID-19 infection. Our multivariable logistic regression analysis that included CHA2DS2VASc score has a relatively good predictive value and if confirmed in other COVID-19 cohorts, may be used to identify patients in whom antiarrhythmic and more aggressive thromboprophylactic strategies can be considered.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2

Abstract Background Even in patients with atrial fibrillation (AF) and low CHA2DS2-VASc scores, it is not always possible to completely rule out left atrial appendage (LAA) thrombus. Further stratification of the risk of LAA thrombosis in these patients remains an important yet unresolved issue. Left ventricular hypertrophy (LVH) is a prognostic risk factor in AF and has been associated with a worse prognosis, particularly in those with low CHA2DS2-VASc scores. Purpose To investigate the clinical significance of echocardiographic LVH for risk stratifying LAA thrombogenic milieu as a surrogate for cardioembolic risk in patients with AF and CHA2DS2-VASc scores of 0–2. Methods This was a single-center, retrospective study. We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. The patients were divided into two groups based on the presence or absence of LVH. Owing to the racial differences in normative left ventricular mass index (LVMI) reference values, LVH was defined in this study using Japanese reference values. LVH was defined as LVMI ≥108 g/m2 for men and ≥98 g/m2 for women. LAA thrombogenic milieu was defined by any of the following findings: (1) thrombus, (2) severe spontaneous echo contrast or sludge, or (3) average LAA flow velocity ≤20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium (LA) were obtained using transthoracic echocardiography. Results The mean age was 61 ± 10 years, and 12.2% were female. Overall, 77 (10.9%) patients were classified into the LVH group, and 41 (5.8%) of patients had LAA thrombogenic milieu. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH (32.5% vs. 2.5%, p&amp;lt;0.001). Figure 1 illustrates the details of the patients with the LAA thrombogenic milieu based on LVH presence and CHA2DS2-VASc scores. The LVH group included six patients with LAA thrombus, even with CHA2DS2-VASc scores of 2, whereas the non-LVH group had no patient with LAA thrombus. Table shows the association of LAA thrombogenic milieu and clinical and echocardiographic parameters by logistic regression analysis; LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and LA volume index). Moreover, LVH provided incremental prognostic value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and LA reservoir strains (p&amp;lt;0.001). These findings are summarized in Figure 2. Conclusion Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

Low rates of haemorrhagic stroke, not increased by age, renal/hepatic impairment, concomitant anti-platelet use and high CHA2DS2-VASc scores, in the 4-year follow-up of ETNA-AF-Europe

Abstract Background Balancing the risks of stroke and bleeding is necessary to optimise oral anticoagulation use in clinical practice. Concerns remain over the increased bleeding risk in patients receiving NOACs, and long-term safety data in this population are limited. Purpose To report annualised rates of haemorrhagic stroke in various sub-populations of patients with atrial fibrillation (AF) treated with edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe, a post-authorisation, observational study conducted across 776 sites from 10 European countries, assessed the risks and benefits of edoxaban use in patients with AF. Here, we present the annualised event rates of haemorrhagic stroke during the 4-year follow-up, that occurred overall (on-/off-edoxaban) and on-edoxaban, including sub-populations stratified by age, renal impairment, hepatic impairment, chronic concomitant antiplatelet use and CHA2DS2-VASc score. Patient characteristics were collected at baseline and annualised event rates were reported for outcomes. Results A total of 13,164 patients were included in the full analysis set. Baseline characteristics are reported in Table 1. The overall and on-edoxaban annualised haemorrhagic stroke rates were low (number of events, % [95% confidence interval]: 36, 0.1 [0.05;0.11] and 31, 0.1 [0.05;0.10] respectively). The overall haemorrhagic stroke rates remained low in subgroups stratified by age (&amp;lt;65 years: 4, 0.1 [0.00;0.11]; ≥65–75 years: 13, 0.1 [0.04;0.13]; ≥75 years: 19, 0.1 [0.05;0.12]), renal impairment (yes: 23, 0.1 [0.05;0.13]; no: 12, 0.1 [0.03;0.11]), hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 35, 0.1 [0.06;0.11]), concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.16]; no: 34, 0.1 [0.05;0.11]) and CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 28, 0.1 [0.06;0.12]; high [&amp;gt;4]: 7, 0.1 [0.03;0.18]) (Figure). Likewise, on-edoxaban haemorrhagic stroke rates were low irrespective of age (&amp;lt;65 years: 3, &amp;lt;0.1 [0.00;0.010; ≥65–75 years: 12, 0.1 [0.04;0.13]; ≥75 years: 16, 0.1 [0.04;0.12]); renal impairment (yes: 20, 0.1 [0.05;0.12]; no: 10, 0.1 [0.02;0.10]); hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 30, 0.1 [0.05;0.11]); chronic concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.18; no: 29, 0.1[0.05;0.10]) or CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 25, 0.1 [0.05;0.12]; High [&amp;gt;4]: 6, 0.1 [0.02;0.17]) (Figure). Conclusions The overall and on-edoxaban annualised rates of haemorrhagic stroke were low and were not increased by non-modifiable risk factors such as age, renal/hepatic impairment, concomitant antiplatelet use and high CHA2DS2-VASc scores during the 4-year follow-up. The overall annualised rates on-edoxaban in ETNA-AF-Europe registry are quite comparable with incidence rates reported in the literature in age-stratified populations (incidence/100 person-years: 55-64 years: 0.06 [0.04-0.07]; 65-74 years: 0.1 [0.09-0.1]; 75-84 years 0.2 [0.1-0.2]).Baseline Characteristics

Prevention of thromboembolic events in atrial fibrillation patients with persistent leaks following the watchman implantation

Abstract Introduction Peri-device leak is not uncommon after percutaneous occlusion of left atrial appendage using the Watchman device. Prior studies have reported the clinical relevance of small leaks (&amp;lt;5mm) as they were associated with a significant increase in ischemic events. Purpose We evaluated the prevalence of stroke in patients with post-watchman leaks on half-dose non-vitamin K oral anticoagulants (HD-NOAC) vs antiplatelet therapy (APT). Methods This consecutive series included post-watchman cases that had a residual leak of ≤5 mm at the 45-day echocardiogram and were unwilling to undergo any leak-closure procedure. Based on their subsequent antithrombotic therapy, they were classified into group 1: HD-NOAC and group 2: dual-APT for 6 months followed by Aspirin only. Patients were closely monitored for thromboembolic (TE) events via telemedicine. Stroke/transient ischemic attacks that occurred while the patients were in full compliance with the anti-thrombotic therapy, were counted as the reportable TE events. Results A total of 141 (age: 66.89± 8.76 years, male: 88 (62.4%), CHA2DS2-VASc score: 3.41 ± 1.56, HAS-BLED: 3.72 ± 1.01) and 154 (age: 72.45 ±7.05 years, male: 99 (64.3%), CHA2DS2-VASc score: 3.75 ± 1.61, HAS-BLED: 3.89 ± 1.05) patients were included in group 1 and 2 respectively. All leaks were between 3-5 mm. TE events were reported in 2 (2/141, 2.12%) patients in group 1 and 9 (9/154, 5.8%) in group 2 while being on antithrombotic therapy (p=04). No residual neurological deficits were detected in the 2 patients from group 1 contrary to the 9 subjects in group 2 that had neurological deficits persistent at follow-up. Of note, 8 (5.6%) patients in group 1 experienced stroke after discontinuing the drug for other medical procedures or due to poor compliance. Conclusion Under full compliance, HD-NOAC is associated with significantly lower TE rate compared to the APT therapy in post-watchman cases with persistent leaks of ≤5 mm. However, discontinuation of the HD-NOAC increases the stroke-risk to a comparable level.

Sex differences in the substrate of atrial fibrillation and the outcome of thoracoscopic ablation

Abstract Background Women with atrial fibrillation (AF) suffer more from AF symptoms, a lower quality of life, and have an enhanced risk of stroke. The AF recurrence after ablation is higher in women than in men. We hypothesize that sex specific differences in the atrial fibrotic substrate underlie these differences in clinical outcome. Here, we sought to characterize atrial fibrosis and fibrosis formation in the left atrial appendage (LAA) of women and men undergoing thoracoscopic ablation of AF. Methods We used the excised LAA of 30 female and 30 male patients with persistent AF undergoing thoracoscopic AF ablation. Patients were matched for age. In addition propensity score matching was also conducted for adjusting intermediary variables such as AF duration, Age ≥ 75, Body mass index (BMI), and CHA2DS2-VASc score ≥ 4. LAAs were stained with picrosirius red to quantify collagen and with vimentin for fibroblasts. Images were analyzed automatically (Image J version 1.50i) using color deconvolution to identify the area fraction of collagen and fibroblast. Results Women had similar age as men (66.4±7.76 vs 66.1 ±7.57, P= 0.85) but had a trend toward more cardiovascular risk factors [CHA2DS2-VASc score ≥ 4, (23.3 vs 6.7)%, P=0.07]. The total percentage of fibroblasts was larger in women 14.98 (9.79-24.95) % than men 13 (5.85-17.46) %, P=.018. In addition, in women fibroblasts were located more in epicardially and endocardially than in the interstitium.[women 8.18 (5.06-13.36) % vs men 6.49 (2.73-9.92) % , P=0.005].There was not a remarkable differences in total amount of collagen between the groups [women 16.03 (9.67-26.98) % vs men 15.50 (9.50-20.90) %, P=0.57 ], but there was a trend towards more epicardial and endocardial collagen in women than men [11.81(5.75-22.11)% vs 10.24 (6.06-15.10) % , P=0.06]. Conclusion We demonstrate more epicardial and endocardial fibroblasts in the LAA of women compared to men with persistent AF. There was similarly a trend towards more epicardia and endocardial but not interstitial collagen deposition. These findings may –at least in part- underlie sex specific differences in AF pathophysiology and ablation outcome.

Improvement of left atrial function after ablation in patients with paroxysmal atrial fibrillation is associated with the presence of heart failure with preserved ejection fraction

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) often coexist and left atrial (LA) function was impaired in both AF and HFpEF. However, It remains unclear if HFpEF is linked to LA function improvement in paroxysmal atrial fibrillation (pxAF) patients post-ablation. Purpose To investigate whether the improvement of LA function after ablation in patients with pxAF combined with HFpEF is better than that in patients without HFpEF. Methods 147 patients with pxAF were enrolled and HFpEF was ascertained based on the H2FPEF score. All patients underwent transthoracic echocardiography (TTE) at baseline and 3 months after ablation. Left atrial volume index (LAVI), left atrial ejection fraction (LAEF) and left atrial peak reservoir strain (LA RS) were measured. Improvement of left atrial function is defined as the difference in the above 3 indicators at baseline and 3 months after ablation. The change of the above atrial functional parameters was compared between patients with high-probability of HFpEF [hp-HFpEF] and medium/low-probability of HFpEF [lp-HFpEF]) in univariate and multivariate analysis. Statistical analyses were conducted using independent samples t-tests, Mann-Whitney U tests, and ANCOVA. Results 147 patients were included (30 hp-HFpEF, 117 lp-HFpEF, mean age 62.6 years, 63.3% men, mean BMI 25.54kg/㎡, mean disease course 28.2 months, mean CHA2DS2-VASc score 1.97). In the univariate analysis, the following factors were significantly different between hp-HFpEF and lp-HFpEF, including BMI (26.95±3.71 vs. 25.18±3.00, p=0.007), CHA2DS2-VASc score (3[3-4] vs. 2[1-2], p＜0.001), LA function at baseline including LAVI (41.59±11.38 vs. 32.57[27.68-41.10], p=0.003), LAEF (45.97±10.26 vs. 57.23±9.08, p＜0.001), LA RS (26.43±10.68 vs. 34.43±10.60, p＜0.001), and difference at baseline and 3 months after ablation in LA function including LAVI (4.92±1.08 vs. 3.33±1.18, p＜0.001), LAEF (13.41±9.71 vs. 2.98±9.69, p＜0.001), LA RS (23.61±10.23 vs. 7.29±6.91, p＜0.001), and in left ventricular (LV) TTE indicators including E/e’ (3.10±2.30 vs. -0.32±2.68, p＜0.001), LV ejection fraction (10.5[7.0-16.5] vs. 2.0[-5.0-6.0], p＜0.001), LV global longitudinal strain (14.94±4.27 vs. 5.15[2.63-8.30], p＜0.001) and LV mass (17.79±28.67 vs 1.50[-8.75-17.00], p=0.006). After adjusted for BMI, CHA2DS2-VASc score, LA function at baseline and difference at baseline and 3 months after ablation in LV TTE indicators, the improvement of LA function 3 months after ablation in patients with hp-HFpEF is better than that in patients with lp-HFpEF: LAVI significantly decreased (4.24±0.21 vs. 3.46± 0.09, p＜0.001), LAEF significantly increased (12.90±2.13 vs. 3.09±0.86, p＜0.001) and LA RS significantly increased (21.44±1.81 vs. 8.02±0.76, p＜0.001) in hp-HFpEF compared with lp-HFpEF. Conclusion Patients with pxAF with hp-HFpEF showed better improvement in LA function after ablation than those with Ip-HFpEF.