Oral Anticoagulation Therapy in Atrial Fibrillation Patients Managed in the Emergency Department Compared to Cardiology Outpatient: Opportunities for Improved Outcomes.

INTRODUCTION: Recent registry data suggests oral anticoagulation (OAC) usage remains suboptimal in atrial fibrillation (AF) patients. The aim of our study was to determine if rates of appropriate use of OAC in individuals with AF differs between the emergency department (ED) and cardiac outpatient clinic (CO). METHODS: This was a retrospective study of consecutive AF patients over a 12-month period. Data from clinical records, discharge summaries and outpatient letters were independently reviewed by two investigators. Appropriateness of OAC was assessed according to the CHA2DS2-VASc score. RESULTS: Of 455 unique ED presentations with AF as a primary diagnosis, 115 patients who were treated and discharged from the ED were included. These were compared to 259 consecutively managed AF patients from the CO. Inappropriate OAC was significantly higher in the ED compared to the CO group (65 vs. 18%, p<0.001). Treatment in the ED was a significant multivariate predictor of inappropriate OAC (odds ratio 8.2 [4.8-17.7], p<0.001). CONCLUSIONS: This patient level data highlights that significant opportunity exists to improve disparities in the use of guideline adherent therapy in the ED compared to CO. There is an urgent need for protocol-driven treatment in the ED or streamlined early follow-up in a specialised AF clinic to address this treatment gap.

Influence of ethnic background on left atrial markers of inflammation, endothelial function and tissue remodelling.

BACKGROUND: It has been suggested that ethnicity can make a significant difference to the likelihood of thromboembolic stroke related to atrial fibrillation. Ethnic differences have been shown to alter inflammatory and haemostatic factors; however, this may all be confounded by differences in cardiovascular risk factors between different ethnicity. The impact of different ethnicities on the thrombogenic profile is not known. The aim of this study was to investigate differences in markers of inflammation, endothelial function and tissue remodelling between Caucasian and Indian populations with supraventricular tachycardia (SVT). METHODS: Patients with structurally normal hearts undergoing catheter ablation for SVT were studied. This study included 23 Australian (Caucasian) patients from the Royal Adelaide Hospital, Adelaide, Australia and 24 Indian (Indian) patients from the Christian Medical College, Vellore, India. Blood samples were collected from the femoral vein, and right and left atria. Blood samples were analysed for the markers of endothelial function (ADMA, ET-1), inflammation (CD40L, VCAM-1, ICAM-1), and tissue remodelling (MMP-9, TIMP-1) using ELISA. RESULTS: The study populations were well matched for cardiovascular risk factors and the absence of structural heart disease. No difference in the echocardiographic measurements between the two ethnicities was found. In this context, there was no difference in markers of inflammation, endothelial function or tissue remodelling between the two SVT populations. CONCLUSION: Caucasian and Indian populations demonstrate similar inflammatory, endothelial function or tissue remodelling profiles. This study suggests a lack of an impact of different ethnicity in these populations in terms of thrombogenic risk.

Alcohol and incident atrial fibrillation - A systematic review and meta-analysis.

BACKGROUND: Whilst high levels of alcohol consumption are known to be associated with atrial fibrillation (AF), it is unclear if any level of alcohol consumption can be recommended to prevent the onset of the condition. The aim of this review is to characterise the association between chronic alcohol intake and incident AF. METHODS AND RESULTS: Electronic literature searches were undertaken using PubMed and Embase databases up to 1 February 2016 to identify studies examining the impact of alcohol on the risk of incident AF. Prospective studies reporting on at least three levels of alcohol intake and published in English were eligible for inclusion. Studies of a retrospective or case control design were excluded. The primary study outcome was development of incident AF. Consistent with previous studies, high levels of alcohol intake were associated with an increased incident AF risk (HR 1.34, 95% CI 1.20-1.49, p<0.001). Moderate levels of alcohol intake were associated with a heightened AF risk in males (HR 1.26, 95% CI 1.04-1.54, p=0.02) but not females (HR 1.03, 95% CI 0.86-1.25, p=0.74). Low alcohol intake, of up to 1 standard drink (SD) per day, was not associated with AF development (HR 0.95, 95% CI 0.85-1.06, p=0.37). CONCLUSIONS: Low levels of alcohol intake are not associated with the development of AF. Gender differences exist in the association between moderate alcohol intake and AF with males demonstrating greater increases in risk, whilst high alcohol intake is associated with a heightened AF risk across both genders.

Integrated care in atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: Atrial fibrillation (AF) is an emerging global epidemic associated with significant morbidity and mortality. Whilst other chronic cardiovascular conditions have demonstrated enhanced patient outcomes from coordinated systems of care, the use of this approach in AF is a comparatively new concept. Recent evidence has suggested that the integrated care approach may be of benefit in the AF population, yet has not been widely implemented in routine clinical practice. We sought to undertake a systematic review and meta-analysis to evaluate the impact of integrated care approaches to care delivery in the AF population on outcomes including mortality, hospitalisations, emergency department visits, cerebrovascular events and patient-reported outcomes. METHODS: PubMed, Embase and CINAHL databases were searched until February 2016 to identify papers addressing the impact of integrated care in the AF population. Three studies, with a total study population of 1383, were identified that compared integrated care approaches with usual care in AF populations. RESULTS: Use of this approach was associated with a reduction in all-cause mortality (OR 0.51, 95% CI 0.32 to 0.80, p=0.003) and cardiovascular hospitalisations (OR 0.58, 95% CI 0.44 to 0.77, p=0.0002) but did not significantly impact on AF-related hospitalisations (OR 0.82, 95% CI 0.56 to 1.19, p=0.29) or cerebrovascular events (OR 1.00, 95% CI 0.48 to 2.09, p=1.00). CONCLUSIONS: The use of the integrated care approach in AF is associated with reduced cardiovascular hospitalisations and all-cause mortality. Further research is needed to identify optimal settings, methods and components of delivering integrated care to the burgeoning AF population.

Obesity and the Risk of Incident, Post-Operative, and Post-Ablation Atrial Fibrillation: A Meta-Analysis of 626,603 Individuals in 51 Studies.

OBJECTIVES: The purpose of this study was to quantify the magnitude of association between incremental increases in body mass index (BMI) and the development of incident, post-operative, and post-ablation atrial fibrillation (AF). BACKGROUND: Obesity has been estimated to account for one-fifth of all AF and approximately 60% of recent increases in population AF incidence. From a public health perspective, obesity, therefore, is a modifiable risk factor that could be profitably targeted. METHODS: A systematic review and meta-analysis was conducted. Medline and EMBASE databases were searched for observational studies reporting data on the association between obesity and incident, post-operative, and post-ablation AF. Studies were included if they reported or provided data allowing calculation of risk estimates. RESULTS: Data from 51 studies including 626,603 individuals contributed to this analysis. There were 29% (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.23 to 1.36) and 19% (OR: 1.19, 95% CI: 1.13 to 1.26) greater excess risks of incident AF for every 5-U BMI increase in cohort and case-control studies, respectively. Similarly, there were 10% (OR: 1.10, 95% CI: 1.04 to 1.17) and 13% (OR: 1.13, 95% CI: 1.06 to 1.22) greater excess risks of post-operative and post-ablation AF for every 5-U increase in BMI, respectively. CONCLUSIONS: Incremental increases in BMI are associated with a significant excess risk of AF in different clinical settings. For every 5-U increase in BMI, there were 10% to 29% greater excess risks of incident, post-operative, and post-ablation AF. By providing a comprehensive and reliable quantification of the relationship between incremental increases in obesity and AF across different clinical settings, our findings highlight the potential for even moderate reductions in population body mass indexes to have a significant effect in mitigating the rising burden of AF.

Thrombogenic Risk in Patients With Atrial Fibrillation: Importance of Comorbid Conditions and Intracardiac Changes.

OBJECTIVES: This study sought to determine the differences between the prothrombotic properties and chamber characteristics in patients with lone atrial fibrillation (AF) and those with AF and comorbidities. BACKGROUND: Thromboembolic risk is increased in patients with AF; however, whether this is due to AF per se or its comorbidities remains unclear. METHODS: A total of 87 patients undergoing ablation were prospectively recruited for the study, including 30 patients with lone AF, 30 patients with AF and comorbidities in sinus rhythm, and 27 patients with left-sided accessory pathways as controls. Blood samples were obtained from the left atrium (LA), right atrium (RA), and femoral vein (FV) after transseptal puncture. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric-dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. RESULTS: Platelet activation in the LA was significantly elevated compared to that in the FV in patients with lone AF and those with AF and comorbidities compared with that in the FV (p < 0.05 respectively). Thrombin generation was significantly elevated in the LA compared with RA in AF patients (p < 0.05). There were no significant differences in P-selectin, TAT, and sCD40L among the 3 groups. However, there was a significant stepwise increase in endothelial dysfunction measured by ADMA from controls to lone AF and then to patients with AF and comorbidities (p < 0.001 between the 2 groups). CONCLUSIONS: Patients with lone AF and those with AF and comorbidities had a greater propensity for atrial thrombogenesis than controls. Prothrombotic risk is greatest in those with comorbid conditions, in whom enhanced thrombogenesis occurs predominantly through increase in endothelial dysfunction.

Underuse and overuse of anticoagulation for atrial fibrillation: A study in Indigenous and non-Indigenous Australians.

BACKGROUND: Atrial fibrillation (AF) is a leading cause of preventable stroke in Australia. Given that anticoagulation therapy can significantly reduce this stroke risk, we sought to characterise anticoagulation use in Indigenous and non-Indigenous Australians with AF. METHODS: Administrative, clinical and prescription data from patients with AF were linked. Anticoagulation use was characterised according to guideline-recommended risk scores and Indigenous status. RESULTS: 19,613 individuals with AF were studied. Despite a greater prevalence of other risk factors, Indigenous Australians were significantly younger than their non-Indigenous counterparts (p<0.001) and thus had lower CHADS2- (1.19±0.32 vs 1.99±0.47, p<0.001) and CHA2DS2VASc-scores (1.47 ± 0.03 vs 2.82 ± 0.08, p<0.001). Correspondingly, the percentage of Indigenous Australians with CHADS2 ≥ 2 (39.6% vs 44.1%, p<0.001) and CHA2DS2VASc-scores ≥ 2 (62.9% vs 78.8%, p<0.001) was also lower. Indigenous Australians, however, had greater rates of under- and over-anticoagulation. Overall, 72.1% and 68.9% of Indigenous and non-Indigenous Australians with CHADS2 scores ≥2, and 76.3% and 71.3% with CHA2DS2VASc scores ≥2, were under-anticoagulated. Similarly, 27.4% and 24.1% of Indigenous and non-Indigenous Australians with CHADS2 scores=0, and 24.0% and 16.7% with CHA2DS2VASc-scores=0, were over-anticoagulated. In multivariate analyses, Indigenous Australians were more likely to receive under- or over-anticoagulation according to CHADS2- or CHA2DS2VASc-score (p=0.045 and p<0.001 respectively). CONCLUSION: Anticoagulation for AF is frequently not prescribed in accordance with guideline recommendations. Under-anticoagulation in those at high stroke risk, and over-anticoagulation in those at low risk, is common and more likely in Indigenous patients with AF. Improving adherence to guideline recommendations for anticoagulation in AF may reduce both ischaemic and haemorrhagic strokes in Indigenous and non-Indigenous Australians.

Atrial fibrillation in Indigenous and non-Indigenous Australians: a cross-sectional study.

OBJECTIVE: To examine the prevalence of atrial fibrillation (AF) and cardiac structural characteristics in Indigenous and non-Indigenous Australians. DESIGN: Retrospective cross-sectional study linking clinical, echocardiography and administrative databases over a 10-year period. SETTING: A tertiary, university teaching hospital in Adelaide, Australia. PARTICIPANTS: Indigenous and non-Indigenous Australians. MAIN OUTCOME MEASURES: AF prevalence and echocardiographic characteristics. RESULTS: Indigenous Australians with AF were significantly younger compared to non-Indigenous Australians (55±13 vs 75±13 years, p<0.001). As a result, racial differences in AF prevalence and left atrial diameter varied according to age. In those under 60 years of age, Indigenous Australians had a significantly greater AF prevalence (2.57 vs1.73%, p<0.001) and left atrial diameters (39±7 vs 37±7 mm, p<0.001) compared to non-Indigenous Australians. In those aged 60 years and above, however, non-Indigenous Australians had significantly greater AF prevalence (9.26 vs 4.61%, p<0.001) and left atrial diameters (39±7 vs 37±7 mm, p<0.001). Left ventricular ejection fractions were less in Indigenous Australians under 60 years of age (49±14 vs 55±11%, p<0.001) and not statistically different in those aged 60 years and above (47±11 vs 52±13, p=0.074) compared to non-Indigenous Australians. Despite their younger age, Indigenous Australians with AF had similar or greater rates of cardiovascular comorbidities than non-Indigenous Australians with AF. CONCLUSIONS: Young Indigenous Australians have a significantly greater prevalence of AF than their non-Indigenous counterparts. In contrast, older non-Indigenous Australians have a greater prevalence of AF compared to their Indigenous counterparts. These observations may be mediated by age-based differences in comorbid cardiovascular conditions, left atrial diameter and left ventricular ejection fraction. Our findings suggest that AF is likely to be contributing to the greater burden of morbidity and mortality experienced by young Indigenous Australians. Further study is required to elucidate whether strategies to prevent and better manage AF in Indigenous Australians may reduce this burden.

Characteristics of ectopic triggers associated with paroxysmal and persistent atrial fibrillation: evidence for a changing role.

BACKGROUND: Atrial premature contractions (APCs) are well described to precede the initiation of paroxysmal atrial fibrillation (pAF). However, whether APC characteristics alter with progression of the arrhythmia is unknown. OBJECTIVE: To determine the APC characteristics in terms of burden and relative coupling interval with progression of the AF disease process. METHODS: Fifty consecutive patients with pAF, 50 consecutive patients with persistent AF (perAF), and 25 age-matched controls underwent clinical review, transthoracic echocardiography, and ambulatory electrocardiogram monitoring. After excluding 29 patients who had AF for the entire recording (n = 24) or unreliable recordings (n = 5), we analyzed data from 49 patients with pAF, 24 patients with perAF, and 23 healthy controls. All normal morphology R-R intervals with a >25% decrease in R-R coupling compared with the previous R-R interval (coupling interval index) were deemed APCs (n = 95,873). RESULTS: The median APC burden was higher in patients with pAF (2 [1-22] APCs/h; P = .004) and perAF (3 [1-6] APCs/h; P = .04) than in controls (1 [0-1] APCs/h) but was not different (P = .66) between the AF subgroups. Patients with pAF had a distinct increase in ectopy burden after 7 PM and elevation throughout the night (P = .002) in comparison with a blunted and complementary temporal response in the perAF cohort (P = .01). Patients with pAF demonstrated a greater proportion of shortly coupled APCs (29% [13-45]; P = .04) compared with persistent arrhythmia (17% [5-29]). CONCLUSIONS: "Real-life" atrial trigger statistics of APC burden, timing, and diurnal rhythms track the transition from a trigger-based, autonomically sensitive paroxysmal arrhythmia to a more substrate-based persistent disease.