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Background: Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to target the underlying arrhythmogenic substrate in atrial fibrillation (AF). Nevertheless, there have been inconsistent results on the impact of MRAs on AF., Objective: We sought to evaluate the effect of MRAs on AF incidence and progression in patients with and without heart failure., Methods: Electronic databases were searched up to September, 2022 for randomized controlled trials (RCTs) that evaluated MRA use and reported AF outcomes. Primary outcome was a composite of new-onset or recurrent AF. Safety outcomes included hyperkalemia and gynecomastia risks. A random-effects meta-analysis estimated pooled odds ratios (OR) and 95% confidence intervals (CI)., Results: 12 RCTs, comprising 11,419 patients treated with various MRAs were included [5960 (52%) on MRA]. On follow-up (6-39 months), 714 (5.5%) patients developed AF. MRA therapy was associated with a 32% reduction in the risk of new-onset or recurrent AF [OR 0.68 (95% CI 0.51-0.92), I 2  = 40%]. On subgroup analysis, the greatest benefit magnitude was demonstrated in reducing AF recurrence [OR 0.50 (95% CI 0.30-0.83)] and among patients with left ventricular dysfunction [OR 0.59 (95% CI 0.40-0.85)]. Gynecomastia, but not hyperkalemia, was associated with MRA use. Meta-regression analysis demonstrated that therapy duration was a significant interaction factor driving the effect size (P interaction  = 0.013)., Conclusion: MRA use is associated with a reduction in AF risk, especially AF progression. A prominent effect is seen in patients with heart failure, further augmented by therapy duration. Prospective trials are warranted to evaluate MRA use as upstream therapy for preventing this common arrhythmia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Aims: Exercise training reduces recurrence of arrhythmia and symptom severity amongst patients with symptomatic, non-permanent atrial fibrillation (AF). However, there is little evidence on whether this effect is modified by patient sex. In a sub-analysis from the ACTIVE-AF (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation) randomized controlled trial, we compared the effects of exercise training on AF recurrence and symptom severity between men and women., Methods and Results: The ACTIVE-AF study randomized 120 patients (69 men, 51 women) with paroxysmal or persistent AF to receive an exercise intervention combining supervised and home-based aerobic exercise over 6 months or to continue standard medical care. Patients were followed over a 12-month period. The co-primary outcomes were recurrence of AF, off anti-arrhythmic medications and without catheter ablation, and AF symptom severity scores. By 12 months, recurrence of AF was observed in 50 (73%) men and 34 (67%) women. In an intention-to-treat analysis, there was a between-group difference in favour of the exercise group for both men [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.29-0.91, P = 0.022] and women (HR 0.47, 95% CI: 0.23-0.95, P = 0.035). At 12 months, symptom severity scores were lower in the exercise group compared with controls amongst women but not for men., Conclusion: An exercise-based intervention reduced arrhythmia recurrence for both men and women with symptomatic AF. Symptom severity was reduced with exercise in women at 12 months. No difference was observed in symptom severity for men., Registration: Australia and New Zealand Clinical Trials Registry: ACTRN12615000734561., Competing Interests: Conflict of interest: C.V.V. reports lecture and/or consulting fees from Novartis. R.M. reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, Pfizer, and Bayer. R.M. reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, and Bayer. D.H.L. reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Boehringer Ingelheim, Bayer, and Pfizer. P.S. reports having served on the advisory board of Boston Scientific, CathRx, Medtronic, Abbott Medical, and PaceMate. P.S. reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston Scientific, Abbott Medical, PaceMate, and CathRx. P.S. reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, Boston Scientific, PaceMate, and Becton Dickinson. All other authors have no disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Atrial fibrillation (AF) and heart failure (HF) portends a poor outcome. The HF universal definition has incorporated Heart Failure with mildly reduced Ejection Fraction (HFmrEF). We sought to evaluate the relationship between AF and different HF subtypes, with emphasis on HFmrEF., Methods: PubMed and Embase databases were searched up to July 2022. Studies that classified HF with EF≥50% as Heart Failure with Preserved Ejection Fraction (HFpEF); EF 40%-49% as HFmrEF; and EF <40% as Heart Failure with Reduced Ejection Fraction (HFrEF) were included., Results: Fifty (50) eligible studies, with 126,720 acute HF and 109,683 chronic HF patients, were included. Ten percent (10%) and 12% of patients constituted HFmrEF subtype in patients with acute and chronic HF, respectively. The AF prevalence was 38% (95%CI [33, 44], I 2 =96.9%) in HFmrEF, as compared to 43% (95%CI [39, 47], I 2 =97.9%) in HFpEF, and 32% (95%CI [29, 35], I 2 =98.6%) in HFrEF in acute HF patients. Meta-regression showed HFmrEF shared age as a determinant for AF prevalence with HFrEF and HFpEF. Similar AF prevalence also was observed in chronic HF. Compared to sinus rhythm, AF was associated with an increased risk of all-cause mortality in all HF subtypes: HFmrEF (n=6; HR 1.28, 95%CI [1.08, 1.51], I 2 =71%), HFpEF (n=10; HR 1.14, 95%CI [1.06, 1.23], I 2 =55%) and HFrEF (n=9; HR 1.11, 95%CI [1.02, 1.21], I 2 =78%)., Conclusion: The prevalence of AF was intermediate for HFmrEF in between HFpEF and HFrEF, with determinants shared with either HF subtype. The co-existence of AF and HF predicts an increased all-cause mortality across all categories of HF. (PROSPERO registry: CRD42021189411)., (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Background: There are limited data on the effect of exercise interventions on atrial fibrillation (AF) recurrence and symptoms., Objectives: The aim of this study was to determine the efficacy of an exercise and physical activity intervention on AF burden and symptoms among patients with symptomatic AF., Methods: This prospective, randomized controlled trial included 120 patients with paroxysmal or persistent, symptomatic AF, randomized 1:1 to receive an exercise intervention, combining home and supervised aerobic exercise over 6 months, or to receive usual care. The coprimary outcomes were: 1) AF recurrence, off antiarrhythmic medications and without catheter ablation; and 2) symptom severity assessed by using a validated questionnaire., Results: By 12 months, freedom from AF was achieved in 24 (40%) of 60 patients in the exercise group and 12 (20%) of 60 patients in the control group (HR: 0.50: 95% CI: 0.33 to 0.78). At 6 months, AF symptom severity was lower in the exercise group compared with the control group (mean difference -2.3; 95% CI: -4.3 to -0.2; P = 0.033). This difference persisted at 12 months (-2.3; 95% CI: -4.5 to -0.1; P = 0.041). Total symptom burden was lower at 6 months in the exercise group but not at 12 months. Peak oxygen consumption was increased in the exercise group at both 6 and 12 months. There were no between-group differences in cardiac structure or function, body mass index, or blood pressure., Conclusions: Participation in an exercise-based intervention over 6 months reduced arrhythmia recurrence and improved symptom severity among patients with AF. (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation [the ACTIVE-AF Study]; ACTRN12615000734561)., Competing Interests: Funding Support and Author Disclosures This study was supported by funding from the National Heart Foundation of Australia through a postdoctoral fellowship to Dr Elliott. Dr Mahajan is supported by a mid-career fellowship from The Hospital Research Foundation. Drs Middeldorp and Gallagher are supported by postdoctoral fellowships from the University of Adelaide. Dr Hendriks is supported by a Future Leader Fellowship from the Australian Heart Foundation. Dr Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia. The University of Adelaide has received on behalf of Dr Mahajan lecture and/or consulting fees from Medtronic, Abbott, Pfizer, and Bayer; and the University of Adelaide has also received on behalf of Dr Mahajan research funding from Medtronic, Abbott, and Bayer. Flinders University has received on behalf of Dr Hendriks lecture and/or consulting fees from Biotronik. The University of Adelaide has received on behalf of Dr Lau lecture and/or consulting fees from Abbott Medical, Boehringer Ingelheim, Bayer, and Pfizer. Dr Sanders has served on the advisory board of Boston Scientific, CathRx, Medtronic, Abbott Medical, and PaceMate. The University of Adelaide has received on behalf of Dr Sanders lecture and/or consulting fees from Medtronic, Boston Scientific, Abbott Medical, PaceMate, and CathRx; the University of Adelaide has also received on behalf of Dr Sanders research funding from Medtronic, Abbott Medical, Boston Scientific, PaceMate, and MicroPort. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Heart rate reserve (HRR) is used to guide exercise training in patients with cardiovascular disease, primarily as a surrogate for oxygen uptake reserve (VO2R) as a marker of metabolic demand. However, the relationship between HRR and VO2R in patients with atrial fibrillation (AF) is not well described. We aimed to assess the validity of HRR as a surrogate for VO2R to guide exercise intensity in AF patients., Methods: One hundred one patients with non-permanent AF undertaking a cardiopulmonary exercise test (CPET) were prospectively enrolled. HR and VO2 values were recorded throughout exercise to determine HRR and VO2R at each workload. Linear regression was used to calculate the slope and y-intercept for HRR versus VO2R with an equivalent slope defined as 1 and y-intercept of 0. The impact of rhythm during exercise, beta blockers and chronotropic incompetence (CI) on the HRR-VO2R relationship was also assessed., Results: The slope of HRR-VO2R was 0.79±0.4, indicating a significant difference from an assumed slope of 1.0 (mean difference: -0.21, 95% CI: -0.30 to -0.12, P<0.001). The mean y-intercept slope was 20.1±41.6, differing significantly from 0 (mean difference: 20.1, 95% CI: 11.9-28.3, P<0.001). The presence of AF during CPET, beta-blockers or chronotropic incompetence did not independently alter the association between VO2R and HRR., Conclusions: HRR is not equivalent to VO2R in AF patients. There was no significant effect of rhythm status, chronotropic incompetence or beta-blockers on this relationship. These findings highlight that the HR prescription of exercise intensity in AF patients should be guided by an individualised HRR-VO2R relationship.

Introduction: Atrial fibrillation (AF) is associated with increased risk of stroke, heart failure and death. Health literacy, an aspect that falls within precision health, has been recognised as an important factor. We will be focusing on the impact of these interventions specifically to AF and its health outcomes., Methods and Analysis: This protocol is informed by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. The results will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to determine the impacts of health literacy interventions on AF outcomes. Searches will be carried out on databases including MEDLINE, EMBASE, Web of Science, CINAHL, Emcare, Cochrane Library and Google Scholar. Citations will be collected via Endnote 20, then into Covidence for duplicate removal, and article screening. Extraction will occur using a standardised extraction tool and studies will be synthesised using best evidence synthesis. Downs and Black's checklist will be used for risk of bias and assessment of overall quality of evidence will use the Grading of Recommendations, Assessment, Development and Evaluation approach., Ethics and Dissemination: Approval from human research ethics committee is not required. Dissemination will occur in peer-reviewed journals and conference presentations., Prospero Registration Number: CRD42022304835., Competing Interests: Competing interests: The University of Adelaide reports receiving on behalf of Dr Mahajan lecture and/or consulting fees from Abbott, Medtronic, Bayer, Biotronik, and Pfizer. The University of Adelaide reports receiving on behalf of Dr Mahajan research funding from Abbott, Bayer, and Medtronic. The remaining authors do not report any conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To systematic review and meta-analyse the association and mechanistic links between atrial fibrillation (AF) and cognitive impairment., Methods and Results: PubMed, EMBASE, and Cochrane Library were searched up to 27 March 2021 and yielded 4534 citations. After exclusions, 61 were analysed; 15 and 6 studies reported on the association of AF and cognitive impairment in the general population and post-stroke cohorts, respectively. Thirty-six studies reported on the neuro-pathological changes in patients with AF; of those, 13 reported on silent cerebral infarction (SCI) and 11 reported on cerebral microbleeds (CMB). Atrial fibrillation was associated with 39% increased risk of cognitive impairment in the general population [n = 15: 2 822 974 patients; hazard ratio = 1.39; 95% confidence interval (CI) 1.25-1.53, I2 = 90.3%; follow-up 3.8-25 years]. In the post-stroke cohort, AF was associated with a 2.70-fold increased risk of cognitive impairment [adjusted odds ratio (OR) 2.70; 95% CI 1.66-3.74, I2 = 0.0%; follow-up 0.25-3.78 years]. Atrial fibrillation was associated with cerebral small vessel disease, such as white matter hyperintensities and CMB (n = 8: 3698 patients; OR = 1.38; 95% CI 1.11-1.73, I2 = 0.0%), SCI (n = 13: 6188 patients; OR = 2.11; 95% CI 1.58-2.64, I2 = 0%), and decreased cerebral perfusion and cerebral volume even in the absence of clinical stroke., Conclusion: Atrial fibrillation is associated with increased risk of cognitive impairment. The association with cerebral small vessel disease and cerebral atrophy secondary to cardioembolism and cerebral hypoperfusion may suggest a plausible link in the absence of clinical stroke. PROSPERO CRD42018109185., Competing Interests: Conflict of interest: D.L. reports having served on the advisory board of Liva Nova and Medtronic. The University of Adelaide reports receiving on behalf of Dr Linz reports lecture and/or consulting fees from LivaNova, Medtronic, Pfizer, and ResMed. The University of Adelaide reports receiving on behalf of Dr Linz research funding from Sanofi, ResMed, and Medtronic. The University of Adelaide reports receiving on behalf of Dr Lau lecture and/or consulting fees from Abbott, Bayer, Boehringer Ingelheim, Biotronik, and Pfizer. The University of Adelaide reports receiving on behalf of Dr Mahajan lecture and/or consulting fees from Abbott, Medtronic, Bayer, and Pfizer. The University of Adelaide reports receiving on behalf of Dr Mahajan research funding from Abbott and Medtronic. All the remaining authors have declared no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Although single ring isolation is an accepted strategy for undertaking pulmonary vein (PV) and posterior wall isolation (PWI) during atrial fibrillation (AF) ablation, the learning curve associated with this technique as well as procedural and clinical success rates have not been widely reported., Methods and Results: Prospectively collected data from 250 consecutive patients undergoing de novo AF ablation using single ring isolation. PWI was achieved in 212 patients (84.8%) and PV isolation without PWI was achieved in 37 patients (14.4%). Thirty-one cases (12.4%) demonstrated inferior line sparing where PWI was achieved without a continuous posterior wall inferior line. A learning curve was observed, with higher rates of PWI (98% last 50 vs. 82% first 50 cases, p = .016), higher rates of inferior line sparing (20% last 50 vs. 8% first 50 cases, p = .071) and lower ablation times (43.8 min (interquartile range [IQR]: 34.6-57.0 min) last 50 versus. 96.5 min (IQR: 80.8-115.8 min) first 50 cases; p < .001). Three (1.3%) major procedure-related complications were observed. Twelve-month, single-procedure freedom from atrial arrhythmia without drugs was 70.5% (95% confidence interval [CI]: 61.5%-77.7%) and 60.0% (95% CI: 50.2%-68.4%) for paroxysmal and persistent/longstanding persistent AF. Twelve-month multi-procedure freedom from atrial arrhythmia was 92.2% (95%CI: 85.6%-95.9%) and 85.6% (95%CI: 77.2%-91.0%) for paroxysmal and persistent/longstanding persistent AF., Conclusion: Employing a single ring isolation approach, PWI can be achieved in most cases. There is a substantial learning curve with higher rates of PWI, reduced ablation times, and higher rates of inferior line sparing as procedural experience grows. Long-term freedom from arrhythmia is comparable to other AF ablation techniques., (© 2022 Wiley Periodicals LLC.)

Introduction: Successful pulmonary vein isolation (PVI) for atrial fibrillation (AF) depends on the formation of durable transmural lesions. Recently, novel indices have emerged to guide lesion delivery. The aim of the systematic review of literature was to determine AF recurrence following ablation guided by indices incorporating force, power and time, and compare acute procedural outcomes and 12-month AF recurrence with ablation guided by contact force (CF) guided only., Methods: PubMed, EMBASE, and Web of Science Core Collection databases were searched on 27 January 2020 using the keywords; catheter ablation, ablation index (AI), lesion size index (LSI), contact force, atrial fibrillation., Results: After exclusions, seven studies were included in the analysis. AI-guided catheter ablation was associated with a 91% (n=5, 0.91 95% CI; 0.88-0.93) and 80% (n=5, 0.80, 95% CI; 0.77-0.84) freedom from AF at 12 months with and without the use of anti-arhythmic drugs respectively. As compared to CF guided ablation, AI-guided catheter ablation was associated with a 49% increase in successful first pass isolation (n=3; RR: 1.49, 95% CI; 1.38, 1.61), a 50% decrease in number of acute reconnections (n=4; RR: 0.50, 95% CI; 0.39-0.65) and a 22% (n=4, RR: 1.22, 95% CI; 1.10-1.35) increase in AF freedom without anti-arrhythmic drugs at 12 months., Conclusions: Radiofrequency ablation guided by AI was associated with higher successful first pass isolation and lower rates of acute reconnection which translates to greater freedom from AF at 12 months [CRD42019131469]., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Background: The epidemiology of atrial fibrillation (AF) amongst Indigenous populations remains poorly characterised. We studied hospitalisations for AF in Central Australia, the most populous Indigenous region in the country., Methods: Patients with a diagnosis of AF admitted to Alice Springs Hospital, the only secondary health care facility and provider of cardiac care in remote Central Australia, were identified from 2006 to 2016. Age and gender-specific hospitalised AF prevalence, comorbidities, and CHA 2 DS 2 -VASc scores were ascertained., Results: Of 57,056 admitted patients over the study period, 1,210 (2.1%; 46% Indigenous) had a diagnosis of AF. For Indigenous and non-Indigenous individuals <45 years, hospitalised AF prevalence per 10,000 population was 105 (CI 84-131) and 50 (CI 36-68) in males (ratio=2.10), and 98 (CI 77-123) and 12 (CI 6-23) in females (ratio=7.92), respectively. For Indigenous and non-Indigenous individuals ≥65 years, hospitalised AF prevalence per 10,000 was 1,577 (CI 1,194-2,026) and 2,326 (CI 2,047-2,623) in males (ratio=0.68), and 1,713 (CI 1,395-2,069) and 1,897 (1,623-2,195) in females (ratio=0.90). Indigenous individuals had higher rates of cardiometabolic comorbidities, particularly at younger ages. CHA 2 DS 2 -VASc scores were greater in Indigenous individuals, particularly those <45 years (2.5±1.5 versus 0.7±1.1, p<0.001)., Conclusions: The prevalence of hospitalised AF amongst Indigenous people in remote Central Australia was significantly higher than in non-Indigenous individuals, particularly in younger age groups and females. Indigenous individuals with hospitalised AF also had a markedly greater prevalence of cardiometabolic comorbidities and elevated stroke risk. These data suggest that AF may be contributing to the gap in morbidity and mortality experienced by Indigenous Australians., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Background: Reduced exercise capacity and exercise intolerance are commonly reported by individuals with atrial fibrillation (AF). Our objectives were to evaluate the contributing factors to reduced exercise capacity and describe the association between subjective measures of exercise intolerance versus objective measures of exercise capacity., Methods: Two hundred and three (203) patients with non-permanent AF and preserved ejection fraction undergoing cardiopulmonary exercise testing (CPET) were recruited. Clinical characteristics, AF-symptom evaluation, and transthoracic echocardiography measures were collected. Peak oxygen consumption (VO 2peak ) was calculated during CPET as an objective measure of exercise capacity. We assessed the impact of 16 pre-defined clinical features, comorbidities and cardiac functional parameters on VO 2peak ., Results: Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO 2peak was 20.3±6.3 mL/kg/min. 24.9% of patients had a VO 2peak considered low (<16 mL/kg/min). In multivariable analysis, echocardiography-derived estimates of elevated left ventricular (LV) filling pressure (E/E') and reduced chronotropic index were significantly associated with lower VO 2peak . The presence of AF at the time of testing was not significantly associated with VO 2peak but was associated with elevated minute ventilation to carbon dioxide production indicating impaired ventilatory efficiency. There was a poor association between VO 2peak and subjectively reported exercise intolerance and exertional dyspnoea., Conclusion: Reduced exercise capacity in AF patients is associated with elevated LV filling pressure and reduced chronotropic response rather than rhythm status. Subjectively reported exercise intolerance is not a sensitive assessment of reduced exercise capacity. These findings have important implications for understanding reduced exercise capacity amongst AF patients and the approach to management in this cohort. (ACTRN12619001343190)., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Prior studies have demonstrated that anticoagulation underutilisation for atrial fibrillation (AF) and elevated stroke risk is common. However, there is little data on factors associated with appropriate anticoagulation, particularly in Indigenous Australians who face a disproportionate burden of AF and stroke. We thus sought to determine factors associated with anticoagulation use in Australians with AF., Design: Administrative, clinical, prescriptive and laboratory data were linked and aggregated over a 12-year period., Setting: Single tertiary teaching hospital., Participants: 19,305 (98%) and 308 (2%) consecutive non-Indigenous and Indigenous Australians with AF identified from administrative databases., Main Outcome Measures: Associations of anticoagulation use according to ethnicity., Results: Significant independent predictors of anticoagulation use included hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.17-1.34; p<0.001), diabetes (OR 1.14, 95% CI 1.05-1.24; p=0.002), heart failure (OR 1.54 95% CI 1.43-1.66; p<0.001) and prior stroke or transient ischaemic attack (OR 2.07, 95% CI 1.84-2.33; p<0.001). In contrast, increasing age (OR 0.99, 95% CI 0.98-0.99; p<0.001), female gender (OR 0.88, 95% CI 0.82-0.93; p<0.001), and vascular disease (OR 0.72, 95% CI 0.64-0.80; p<0.001) were significant predictors of no anticoagulation. Hypertension was associated with less anticoagulation use in Indigenous compared to non-Indigenous Australians (p=0.02)., Conclusions: Anticoagulation for AF was suboptimal in both Indigenous and non-Indigenous Australians. Older age, female gender, and comorbid vascular disease were found to be negatively associated with anticoagulation. Importantly, hypertension may also be under-recognised as a stroke risk factor in Indigenous Australians. Future efforts to encourage anticoagulation use in accordance with guideline recommendations is likely to reduce the burden of AF-related stroke in both Indigenous and non-Indigenous populations., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Objectives: This study sought to evaluate the effect of weight loss on the atrial substrate for atrial fibrillation (AF)., Background: Whether weight loss can reverse the atrial substrate of obesity is not known., Methods: Thirty sheep had sustained obesity induced by ad libitum calorie-dense diet over 72 weeks. Animals were randomized to 3 groups: sustained obesity and 15% and 30% weight loss. The animals randomized to weight loss underwent weight reduction by reducing the quantity of hay over 32 weeks. Eight lean animals served as controls. All were subjected to the following: dual-energy x-ray absorptiometry, echocardiogram, cardiac magnetic resonance, electrophysiological study, and histological and molecular analyses (fatty infiltration, fibrosis, transforming growth factor β1, and connexin 43)., Results: Sustained obesity was associated with increased left atrium (LA) pressure (p < 0.001), inflammation (p < 0.001), atrial transforming growth factor β1 protein (p < 0.001), endothelin-B receptor expression (p = 0.04), atrial fibrosis (p = 0.01), epicardial fat infiltration (p < 0.001), electrophysiological abnormalities, and AF burden (p = 0.04). Connexin 43 expression was decreased in the obese group (p = 0.03). In this obese ovine model, 30% weight reduction was associated with reduction in total body fat (p < 0.001), LA pressure (p = 0.007), inflammation (p < 0.001), endothelin-B receptor expression (p = 0.01), atrial fibrosis (p = 0.01), increase in atrial effective refractory period (cycle length: 400 and 300 ms; p < 0.001), improved conduction velocity (cycle length: 400 and 300 ms; p = 0.01), decreased conduction heterogeneity (p < 0.001), and decreased AF inducibility (p = 0.03). Weight loss was associated with a nonsignificant reduction in epicardial fat infiltration in posterior LA (p = 0.34)., Conclusions: Weight loss in an obese ovine model is associated with structural and electrophysiological reverse remodeling and a reduced propensity for AF. This provides evidence for the direct role of obesity in AF substrate and the role of weight reduction in patients with AF., Competing Interests: Funding Support and Author Disclosures This study was supported by funds from the Centre of Heart Rhythm Disorders at the University of Adelaide. The sponsor of the study is the University of Adelaide. Several of the authors are employees of the University of Adelaide. The sponsor has had no direct involvement in the management or outcomes of the study. Drs. Mahajan and Lau are supported by the Mid-Career Fellowships from The Hospital Research Foundation. Dr. Lau is supported by the Robert J. Craig Lectureship from the University of Adelaide. Dr. Samuel is supported by an National Health and Medical Research Council Senior Research Fellowship. Dr. Patel is supported by a Monash University MBio Postgraduate Discovery Scholarship. Drs. Kalman and Sanders are supported by Practitioner Fellowships from the National Health and Medical Research Council. Dr. Sanders is supported by the National Heart Foundation of Australia. The University of Adelaide has received on behalf of Dr. Mahajan lecture and/or consulting fees from Abbott, Medtronic, Bayer, and Pfizer and research funding from Abbott and Medtronic and Bayer. Dr. Mahajan has served on the Advisory Board of Abbott. The University of Adelaide has received on behalf of Dr. Sanders lecture and/or consulting fees from Medtronic, Abbott, and Boston Scientific and research funding from Medtronic, Abbott, Boston Scientific, and Microport. Dr. Sanders has served on the Advisory Board of Medtronic, Abbott, Boston Scientific, Pacemate, and CathRx. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Obesity and metabolic syndrome are both associated with atrial fibrillation (AF). Recent research has revealed new insights into the effects of cardiac and noncardiac adipose tissue in mediating these associations. Cardiac adipose tissue, such as epicardial fat, is a powerful predictor of AF and leads to myocardial fatty infiltration and adipokine-induced fibrosis. Increases in noncardiac adipose tissue cause deleterious metabolic, neurohormonal, hemodynamic, and structural changes. Weight loss leads to a regression of adiposity-related fibrosis, structural abnormalities, conduction abnormalities, and reduction in AF burden. As a result, weight loss and risk factor treatment is now an established pillar of AF management., Competing Interests: Potential conflict of interest Dr C.X. Wong reports that the University of Adelaide has received on his behalf lecture, travel, and/or research funding from Abbott Medical, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and St. Jude Medical. Dr R. Mahajan reports having served on the advisory board of Abbott Medical and Medtronic. Dr R. Mahajan reports that the University of Adelaide has received on his behalf lecture fees from Medtronic, Abbott Medical, Pfizer, and Bayer. Dr R. Mahajan also reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, and Bayer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Anemia frequently coexists with atrial fibrillation (AF) and has been variably associated with worse outcomes. We performed a systematic review and meta-analysis to comprehensively assess the effect of anemia on mortality, stroke/systemic thromboembolism, and bleeding events in patients with AF., Methods: MEDLINE and Embase were searched from inception until May 2020. Studies examining associations of anemia with the above outcomes in AF patients were included, and maximally adjusted hazard ratios (HRs) meta-analysed. PROSPERO registration number CRD42020171113., Results: Twenty-eight studies involving 365 484 patients (41% female, mean age 74.7 years) were included. The average study follow-up ranged from 0.2 to 4.0 years, and the prevalence of anemia was 16%. Anemia was associated with a 78% increase in all-cause mortality (HR, 1.78; 95% confidence interval [CI], 1.44-2.20), 60% increase in cardiovascular mortality (HR, 1.60; 95% CI, 1.17-2.19), 134% increase in noncardiovascular mortality (HR, 2.34; 95% CI, 1.58-3.47) 15% increase in stroke/systemic thromboembolism (HR, 1.15; 95% CI, 1.01-1.31), 78% increase in major bleeding (HR, 1.78; 95% CI, 1.54-2.05), and 77% increase in gastrointestinal bleeding (HR, 1.77; 95% CI, 1.23-2.55). Sensitivity analyses including studies that reported odds ratios did not result in any material change., Conclusion: Anemia is a frequently observed comorbidity in patients with AF, and is associated with an increased risk of all-cause, cardiovascular and noncardiovascular mortality, stroke/systemic thromboembolism, and major and gastrointestinal bleeding. Future studies are required to explore the causes of anemia in AF, and whether investigation and treatment may be clinically beneficial in affected individuals., (© 2021 Wiley Periodicals LLC.)

Background: Studies have shown that suboptimal anticoagulation quality, as measured by time in therapeutic range (TTR), affects a significant percentage of patients with atrial fibrillation (AF). However, TTR has not been previously characterised in Indigenous Australians who experience a greater burden of AF and stroke., Method: Indigenous and non-Indigenous Australians with AF on warfarin anticoagulation therapy were identified from a large tertiary referral centre between 1999 and 2012. Time in therapeutic range was calculated as a proportion of daily international normalised ratio (INR) values between 2 and 3 for non-valvular AF and 2.5 to 3.5 for valvular AF. INR values between tests were imputed using the Rosendaal technique. Linear regression models were employed to characterise predictors of TTR., Results: Five hundred and twelve (512) patients with AF on warfarin were included (88 Indigenous and 424 non-Indigenous). Despite younger age (51±13 vs 71±12 years, p<0.001), Indigenous Australians had greater valvular heart disease, diabetes, and alcohol excess compared to non-Indigenous Australians (p<0.05 for all). Time in therapeutic range was significantly lower in Indigenous compared to non-Indigenous Australians (40±29 vs 50±31%, p=0.006). Univariate predictors of poorer TTR included Indigenous ethnicity, younger age, diuretic use, and comorbidities, such as valvular heart disease, heart failure and chronic obstructive pulmonary disease (p<0.05 for all). Valvular heart disease remained a significant predictor of poorer TTR in multivariate analyses (p=0.004)., Conclusion: Indigenous Australians experience particularly poor warfarin anticoagulation quality. Our data also suggest that many non-Indigenous Australians spend suboptimal time in therapeutic range. These findings reinforce the importance of monitoring warfarin anticoagulation quality to minimise stroke risk., Competing Interests: Potential Conflict of Interest Dr Lau reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Bayer, Boehringer Ingelheim, Biotronik, Medtronic and Pfizer. Dr Sanders reports having served on the advisory board of Biosense-Webster, Medtronic, St Jude Medical, Boston Scientific and CathRx. Dr Sanders reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic, St Jude Medical, and Boston Scientific. Dr Sanders reports that the University of Adelaide has received on his behalf research funding from Medtronic, St Jude Medical, Boston Scientific, Biotronik and LivaNova. Dr Wong reports that the University of Adelaide has received on his behalf lecture, travel and/or research funding from Abbott, St Jude Medical, Bayer, Novartis, Servier, Boehringer Ingelheim, and Medtronic., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)

Objective: To undertake a systematic review and meta-analysis examining the impact of polypharmacy on health outcomes in atrial fibrillation (AF)., Data Sources: PubMed and Embase databases were searched from inception until 31 July 2019. Studies including post hoc analyses of prospective randomised controlled trials or observational design that examined the impact of polypharmacy on clinically significant outcomes in AF including mortality, hospitalisations, stroke, bleeding, falls and quality of life were eligible for inclusion., Results: A total of six studies were identified from the systematic review, with three studies reporting on common outcomes and used for a meta-analysis. The total study population from the three studies was 33 602 and 37.2% were female. Moderate and severe polypharmacy, defined as 5-9 medicines and >9 medicines, was observed in 42.7% and 20.7% of patients respectively, and was associated with a significant increase in all-cause mortality (Hazard ratio [HR] 1.36, 95% CI 1.20 to 1.54, p<0.001; HR 1.84, 95% CI 1.40 to 2.41, p<0.001, respectively), major bleeding (HR 1.32, 95% CI 1.14 to 1.52, p<0.001; HR 1.68, 95% CI 1.35 to 2.09, p<0.001, respectively) and clinically relevant non-major bleeding (HR 1.12, 95% CI 1.03 to 1.22, p<0.01; HR 1.48, 95% CI 1.33 to 1.64, p<0.01, respectively). There was no statistically significant association between polypharmacy and stroke or systemic embolism or intracranial bleeding. Among other examined outcomes, polypharmacy was associated with cardiovascular death, hospitalisation, reduced quality of life and poorer physical function., Conclusions: Polypharmacy is highly prevalent in the AF population and is associated with numerous adverse outcomes., Prospero Registration Number: CRD42018105298., Competing Interests: Competing interests: CXW reports that the University of Adelaide has received lecture, travel and research funding on his behalf from Novartis, Servier, Boehringer Ingelheim and Medtronic. RM reports that the University of Adelaide has received lecture fees and research funding on his behalf from Medtronic and St Jude Medical. PS reports having served on the advisory board of Biosense Webster, Medtronic, St Jude Medical and CathRx. PS reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic and St Jude Medical. PS reports that the University of Adelaide has received on his behalf research funding from Medtronic, St Jude Medical, Boston Scientific, Biotronik and LivaNova. JMH reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic and Pfizer/BMS., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the potential association of atrial fibrillation (AF) to syncope and falls, we undertook a systematic review and meta-analysis given the increasing prevalence of AF in older adults as well as emerging data that it is a risk factor for dementia., Patients and Methods: CENTRAL, PubMed, and EMBASE databases were searched from inception to January 31, 2019, to retrieve relevant studies. Search terms consisted of MeSH, tree headings, and keywords relating patients with "AF," "falls," "syncope," and "postural hypotension." When possible; results were pooled using a random-effects model., Results: A total of 10 studies were included, with 7 studies (36,444 patients; mean ± SD age, 72±10 years) reporting an association between AF and falls and 3 studies (6769 patients; mean ± SD age, 65±3 years) reporting an association between AF and syncope. Pooled analyses demonstrate that AF is independently associated with falls (odds ratio, 1.19; 95% CI, 1.07-1.33; P=.001) and syncope (odds ratio, 1.88; 95% CI, 1.20-2.94; P=.006). There was overall moderate bias and low-moderate heterogeneity (I 2 =37%; P=.11) for falls and moderate bias with low statistical heterogeneity (I 2 =0%; P=.44) for syncope. Persistent AF, but not paroxysmal AF, was associated with orthostatic intolerance in 1 study (4408 patients; mean ± SD age, 66±6 years)., Conclusion: AF is independently associated with syncope and falls in older adults. Further studies are needed to delineate mechanistic links and to guide management to improve outcomes in these patients., Trial Registration: PROSPERO: trial identifier: CRD4201810721., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) management guidelines recommend screening for symptoms of sleep-disordered breathing (SDB). We aimed to assess the role of self-reported daytime sleepiness in detection of patients with SDB and AF., Methods: A total of 442 consecutive ambulatory patients with AF who were considered candidates for rhythm control and underwent polysomnography comprised the study population. The utility of daytime sleepiness (quantified by the Epworth Sleepiness Scale [ESS]) to predict any (apnea-hypopnea index [AHI] ≥ 5), moderate-to-severe (AHI ≥ 15), and severe (AHI ≥ 30) SDB on polysomnography was tested., Results: Mean age was 60 ± 11 years and 69% patients were men. SDB was present in two-thirds of the population with 33% having moderate-to-severe SDB. Daytime sleepiness was low (median ESS = 8/24) and the ESS poorly predicted SDB, regardless of the degree of SDB tested (area under the curve: 0.48-0.56). Excessive daytime sleepiness (ESS ≥ 11) was present in 11.9% of the SDB population and had a negative predictive value of 43.1% and a positive predictive value of 67.5% to detect moderate-to-severe SDB. Male gender (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.4-3.8, P = 0.001), obesity (OR: 3.5, 95% CI: 2.3-5.5, P < 0.001), diabetes (OR: 2.3, 95% CI: 1.2-4.4, P = 0.08), and stroke (OR: 4.6, 95% CI: 1.7-12.3, P = 0.002) were independently associated with an increased likelihood of moderate-to-severe SDB., Conclusions: In an ambulatory AF population, SDB was common but most patients reported low daytime sleepiness levels. Clinical features, rather than daytime sleepiness, were predictive of patients with moderate-to-severe SDB. Lack of excessive daytime sleepiness should not preclude patients from being investigated for the potential presence of concomitant SDB., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Education has long been recognized as an important component of chronic condition management. Whereas education has been evaluated in atrial fibrillation (AF) populations as part of multifaceted interventions, it has never been tested as a single entity. The aim of this review is to describe the rationale for and role of education as part of comprehensive AF management. The development and use of educational material as part of the intervention of a randomized controlled trial, the HELP-AF (Home-Based Education and Learning Program in AF) study, will be described. This study was designed to determine the impact of a home-based structured educational program on outcomes in individuals with AF. An educational resource was developed to facilitate delivery of 4 key messages targeted at empowering individuals to self-manage their condition. The key messages focused on strategies for managing future AF episodes, the role of pharmacotherapy in the treatment of AF, the appropriate use of medicines to manage stroke risk and the role of cardiovascular risk factor management in AF. To support structured educational visiting, an educational booklet titled Living Well With Atrial Fibrillation (AF) was developed by a multidisciplinary team and was further refined following input from expert clinicians and patient interviews. Using a structured educational visiting approach, education was delivered by trained clinicians within the patient's home., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm., Methods: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups., Results: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group ( P <0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups., Conclusions: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.

Objective: The aim of this study is to characterise hospitalisations due to atrial fibrillation (AF) compared with two other common cardiovascular conditions, myocardial infarction (MI) and heart failure (HF), in addition to the associated economic burden of these hospitalisations and contribution of AF-related procedures., Methods: The primary outcome measure was the rate of increase of AF, MI and HF hospitalisations from 1993 to 2013. The rate of increase of AF-related procedures including cardioversion and ablation were also collected, in addition to direct costs associated with hospitalisations for each of these three conditions., Results: AF hospitalisations increased 295% over the 21-year period to a total of 61 424 in 2013. In comparison, MI and HF hospitalisations increased by only 73% and 39%, respectively, over the same period. Considering population changes, there was an annual increase in AF hospitalisations of 5.2% (incidence rate ratio [IRR] 1.052; 95% CI 1.046 to 1.059; p<0.001). In contrast, there was a 2.2% increase per annum for MI (IRR 1.022; 95% CI 1.017 to 1.027; p<0.001) and negligible annual change for HF hospitalisations (IRR 1.000; 95% CI 0.997 to 1.002; p=0.78). Cardioversion and AF ablation increased by 10% and 26% annually, respectively. AF hospitalisation costs rose by 479% over the 21-year period, an increase that was more than double that of MI and HF., Conclusions: The burden of AF hospitalisations continues to rise unabated. AF has now surpassed both MI and HF hospitalisations and represents a growing cost burden. New models of healthcare delivery are required to stem this growing healthcare burden., Competing Interests: Competing interests: PS reports having served on the advisory board of Biosense-Webster, Medtronic, St Jude Medical, Boston Scientific and CathRx. PS reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic, St Jude Medical and Boston Scientific. PS reports that the University of Adelaide has received on his behalf research funding from Medtronic, St Jude Medical, Boston Scientific, Biotronik and LivaNova. CXW reports that the University of Adelaide has received on his behalf lecture, travel and/or research funding from Novartis, Servier, Boehringer-Ingelheim and Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The posterior left atrium is an arrhythmogenic substrate that contributes to the initiation and maintenance of atrial fibrillation (AF); however, the feasibility, safety, and efficacy of posterior wall isolation (PWI) as an AF ablation strategy has not been widely reported., Methods: We undertook a systematic review and meta-analysis of studies performing PWI to assess (1) acute procedural success including the ability to achieve PWI and the number of procedure-related complications, (2) Long-term, clinical success including rates of arrhythmia recurrence and posterior wall reconnection, and (3) The efficacy of PWI compared with pulmonary vein isolation on preventing arrhythmia recurrence. MEDLINE, EMBASE, and Web of Science databases were searched in May 2018 to retrieve relevant studies. Results were pooled using a random effects model., Results: Seventeen studies (13 box isolation, 3 single ring isolation, and 1 debulking ablation) comprising 1643 patients (31.3% paroxysmal AF, left atrial diameter 41±3.1 mm) were included in the final analysis. In studies focusing specifically on PWI, the acute procedural success rate for achieving PWI was 94.1% (95% CI, 87.2%-99.3%). Single-procedure 12-month freedom from atrial arrhythmia was 65.3% (95% CI, 57.7%-73.9%) overall and 61.9% (54.2%-70.8%) for persistent AF. Randomized control trials comparing PWI to pulmonary vein isolation (3 studies, 444 patients) yielded conflicting results and could not confirm an incremental benefit to PWI. Fifteen major complications (0.1%), including 2 atrio-esophageal fistulas, were reported., Conclusions: PWI as an end point of AF ablation can be achieved in a large proportion of cases with good rates of 12-month freedom from atrial arrhythmia. Although the procedure-related complication rate is low, it did not eliminate the risk of atrio-esophageal fistula. Registration: URL: http://www.crd.york.ac.uk/prospero. PROSPERO registration number: CRD42018107212.

Background: Atrial fibrillation (AF) is common after pacemaker implantation. However, the impact of pacemaker algorithms in AF prevention is not well understood., Objective: The purpose of this study was to evaluate the role of pacing algorithms in preventing AF progression., Methods: A systematic search of articles using the PubMed and Embase databases resulted in a total of 754 references. After exclusions, 21 randomized controlled trials (8336 patients) were analyzed, comprising studies reporting ventricular pacing percentage (VP%) (AAI vs DDD, n = 1; reducing ventricular pacing [RedVP] algorithms, n = 2); and atrial pacing therapies (atrial preference pacing [APP], n = 14; atrial antitachycardia pacing [aATP]+APP, n = 3; RedVP+APP+aATP, n = 1)., Results: Low VP% (<10%) lead to a nonsignificant reduction in the progression of AF (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.57-1.13; P = .21; I 2 = 67%) compared to high VP% (>10%). APP algorithm reduced premature atrial complexes (PAC) burden (mean difference [MD] -1117.74; 95% CI -1852.36 to -383.11; P = .003; I 2 = 67%) but did not decrease AF burden (MD 8.20; 95% CI -5.39 to 21.80; P = .24; I 2 = 17%) or AF episodes (MD 0.00; 95% CI -0.24 to 0.25; P = .98; I 2 = 0%). Similarly, aATP+APP programming showed no significant difference in AF progression (odds ratio 0.65; 95% CI 0.36-1.14; P = .13; I 2 = 61%). No serious adverse events related to algorithm were reported., Conclusion: This meta-analysis of randomized controlled trials demonstrated that algorithms to reduce VP% can be considered safe. Low burden VP% did not significantly suppress AF progression. The atrial pacing therapy algorithms could suppress PAC burden but did not prevent AF progression., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine night-to-night variability in the severity of sleep-disordered breathing (SDB) and the dynamic intraindividual relationship to daily risk of incident atrial fibrillation (AF) by using simultaneous long-term day-by-day SDB and AF monitoring., Background: Night-to-night variability in SDB severity may result in a dynamic exposure to SDB related conditions impacting the timing and extent of cardiovascular responses., Methods: This study was an observational cohort study. Daily data for AF burden and average respiratory disturbance index (RDI) were extracted from pacemakers capable of monitoring nightly SDB and daily AF burden in 72 patients. Nightly RDI values were grouped into quartiles of severity within each patient. AF burdens of >5 min, >1 h, and >12 h were the outcome variables., Results: A total of 32% of patients had a mean RDI of ≥20/h, indicative of overall severe SDB. There was significant night-to-night variation in RDI reflected by an absolute SD of ±6.3 events/h (range 2 to 14 events/h) within any given patient. Within each patient, the nights with the highest RDI (in their highest quartile) conferred a 1.7-fold (1.2 to 2.2; p < 0.001), 2.3-fold (1.6 to 3.5; p < 0.001), and 10.2-fold (3.5 to 29.9; p < 0.001) increase risk of having at least 5 min, 1 h, and 12 h, respectively, of AF during the same day compared with the best sleep nights (in their lowest quartiles)., Conclusions: There is considerable night-to-night variability in SDB severity which cannot be detected by 1 single overnight sleep study. SDB burden may be a better metric with which to assess the extent of dynamic SDB related cardiovascular responses such as daily AF risk than the categorical diagnosis of SDB. (Night-to-Night Variability in Severity of Sleep Apnea and Daily Dynamic Atrial Fibrillation Risk [VARIOSA-AF]; ACTRN 12618000757213)., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Reentrant circuits are considered to be critically dependent on a single protected slow conducting isthmus., Objective: The purpose of this study was to investigate conduction properties and electrogram (EGM) characteristics of the entire circuit in localized atrial reentrant circuits using high-resolution mapping., Methods: Fifteen localized reentrant atrial tachycardias were studied with high-resolution mapping (Rhythmia). EGMs along the entire circuit were analyzed offline for fractionation, duration, and amplitude. Maps were exported to MATLAB (MathWorks) to measure bipolar voltage and conduction velocities (CVs) within the circuit. Slow conduction was defined as <30 cm/s., Results: Fifteen localized re-entrant circuits (12 left atrial, 3 right atrial) with mean cycle length 273 ± 40 ms were analyzed using high-resolution maps (22,389 ± 13,375 EGMs). A mean of 4.5 ± 1.6 slow conduction corridors were identified per circuit. Although the entire circuit was of low voltage, the bipolar voltage in slow conducting corridors was significantly lower than the rest of the circuit (0.22 ± 0.20 mV vs 0.50 ± 0.48 mV; P <.001). The mean conduction velocity of the circuit, excluding slow conduction areas, was 90.3 ± 34.3 cm/s vs 13.9 ± 3.5 cm/s (P <.001) in the slow conduction corridors. EGM analysis at the slowest conduction corridors demonstrated fractionation (100%) with longer EGM duration compared to the other slow conduction corridors along the circuit (99 ± 9 ms vs 74 ± 11 ms; P = .003)., Conclusion: In contrast to current understanding, localized atrial reentrant circuits have multiple sequential "corridors" of very slow conduction (2-7) that contribute to maintenance of arrhythmia. The localized reentry occurs in low-voltage areas, with voltage further reduced in these multiple slow conducting corridors., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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 CHA 2 DS 2 -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., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objectives: Atrial fibrillation is treated surgically by creating conduction block lesions. Radiofrequency (RF) lesions have reduced efficacy compared to 'cut-and-sew'. Catheter ablation studies demonstrate a relationship between lesion depth and contact force. We hypothesized that contact force and lesion depth are dependent on design of the bipolar surgical RF clamps., Methods: Hinged and parallel jaw style RF clamps were studied. Muscle samples were clamped with pressure-sensitive film at increasing tissue thicknesses. Films were analysed determining clamp pressure profiles. A sheep model was utilized for ablation testing using each clamp style until the device indicated transmurality. Separate muscle areas had 1, 2 or 3 burns applied. The muscle was excised, sectioned every 1 cm and stained for lesion depth and fat thickness analysis., Results: Pressure profiling comparing the proximal and distal segments of each clamp style demonstrated only one statistically significant difference in the parallel clamp; the hinged clamp had statistically significant differences (P ≤ 0.03) for all tissue thicknesses. There was no evidence for differences in the proximal lesion depth of both clamps (P = 0.13) but deeper distally in the parallel clamp (10.17 mm vs 8.02 mm, P = 0.003). The logistic regression analysis demonstrated increased odds of transmurality with parallel clamps at 1, 2 or 3 burns (P = 0.03, P = 0.003 and P = 0.002). Every 1 mm increase in overlying fat decreased likelihood of transmurality by 11% (P < 0.05)., Conclusions: The parallel and hinged clamps have different pressure profiles with higher likelihood of transmurality using the parallel clamp. Fat reduces the ability of RF to deliver a transmural lesion. These findings have implications for optimal surgical RF ablation technique.

Background: Sleep-disordered breathing (SDB) is highly prevalent in patients with atrial fibrillation (AF) and its treatment can improve rhythm control. Polysomnography (PSG) is the gold standard for the diagnosis of SDB but its high cost and limited availability constrain its role as a standard SDB screening tool. We sought to assess the diagnostic utility of overnight oximetry in predicting SDB in AF patients., Methods: We analyzed prospectively collected data on 439 patients with documented AF (62% paroxysmal AF) who underwent PSG. Overnight oximetry was used to determine the oxygen desaturation index (ODI, number of desaturation/h) by a novel automated computer algorithm. ODI was validated against PSG derived apnea-hypopnea index (AHI)., Results: The sample consisted of 69% men with a mean age of 59.9 ± 11.3 years and body mass index of 30 ± 5 kg/m 2 . The median AHI was 9.5 [3.6-21.0]/h and the prevalence of moderate (AHI 15-29/h) and severe SDB (AHI ≥ 30/h) was 17.3% and 16.6% respectively. The ODI was able to detect moderate-to-severe SDB (AHI ≥ 15/h; area under the receiver-operating-characteristic curve (AUC): 0.951, 95% CI: 0.929-0.972) and severe SDB (AHI ≥ 30/h; 0.932, 95% CI: 0.895-0.968) with high diagnostic accuracy. An ODI cut-off of 4.1/h resulted in a 91% sensitivity and 83% specificity in discriminating between patients with and without AHI ≥ 15/h. An ODI of 7.6/h yielded a sensitivity and specificity for AHI ≥ 30/h of 89% and 83%, respectively., Conclusions: ODI derived from a simple and low-cost overnight oximetry can be used as an accessible and reliable screening tool, particularly to rule out SDB., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Atrial fibrillation (AF) is a progressive disease. Obesity is associated with progression of AF. This study evaluates the impact of weight and risk factor management (RFM) on progression of the AF., Methods and Results: As described in the Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up (LEGACY) Study, of 1415 consecutive AF patients, 825 had body mass index ≥ 27 kg/m2 and were offered weight and RFM. After exclusion, 355 were included for analysis. Weight loss was categorized as: Group 1 (<3%), Group 2 (3-9%), and Group 3 (≥10%). Change in AF type was determined by clinical review and 7-day Holter yearly. Atrial fibrillation type was categorized as per the Heart Rhythm Society consensus. There were no differences in baseline characteristic or follow-up duration between groups (P = NS). In Group 1, 41% progressed from paroxysmal to persistent and 26% from persistent to paroxysmal or no AF. In Group 2, 32% progressed from paroxysmal to persistent and 49% reversed from persistent to paroxysmal or no AF. In Group 3, 3% progressed to persistent and 88% reversed from persistent to paroxysmal or no AF (P < 0.001). Increased weight loss was significantly associated with greater AF freedom: 45 (39%) in Group 1, 69 (67%) in Group 2, and 116 (86%) in Group 3 (P ≤ 0.001)., Conclusion: Obesity is associated with progression of the AF disease. This study demonstrates the dynamic relationship between weight/risk factors and AF. Weight-loss management and RFM reverses the type and natural progression of AF.

Objectives: The aims of the study were to characterize: 1) electrical and electroanatomical remodeling in patients with atrial fibrillation (AF) with obesity; and 2) the impact of epicardial fat depots on adjacent atrial tissue., Background: Obesity is associated with an increased risk of AF., Methods: A total of 115 patients with AF who underwent AF ablation were screened. After exclusion, 26 patients were divided into 2 groups (obese: body mass index [BMI] ≥27 kg/m 2 and reference: BMI <27 kg/m 2 ). They underwent cardiac magnetic resonance (CMR) imaging and electroanatomic mapping of the left atrium (LA) in sinus rhythm before AF ablation. Atrial and ventricular epicardial adipose tissue (EAT) were assessed by CMR. The following electrophysiological parameters were assessed: global and regional voltage, conduction velocity (CV), electrogram fractionation, and CV heterogeneity. In addition, the regional relationship between LA EAT depots and the electrophysiological substrate was evaluated., Results: The BMIs of the obese and reference groups were 30.2 ± 2.6 and 25.2 ± 1.3 kg/m 2 , respectively (p < 0.001). There was no difference in the left ventricular ejection fraction and a nonsignificant increase in LA size with obesity. Obesity was associated with increase in all measures of EAT (p < 0.05), with a predominant distribution adjacent to the posterior LA and the atrioventricular groove. Obesity was associated with reduced global CV (0.86 ± 0.31 m/s vs. 1.26 ± 0.29 m/s; p < 0.001), with a nonsignificant increase in conduction heterogeneity (p = 0.10), increased fractionation (54 ± 17% vs. 25 ± 10%; p < 0.001), and regional alteration in voltage (p < 0.001). Although the global LA voltage was preserved, there was greater voltage heterogeneity (p = 0.001) and increased low-voltage areas (13.9% vs. 3.4%; p < 0.001) in the obese group compared with the reference group. The low voltage areas were predominantly seen in the posterior and/or inferior LA, which was similar to location of EAT on CMR imaging. Among various measures of obesity, LA EAT volume correlated best with posterior LA fractionation (r 2  = 0.55 for LA EAT volume vs. r 2  = 0.36 for BMI) and CV (r 2  = 0.31 for LA EAT volume vs. r 2  = 0.22 for BMI)., Conclusions: Obesity is associated with electroanatomical remodeling of the atria, with areas of low voltage, conduction slowing, and greater fractionation of electrograms. These changes were more pronounced in regions adjacent to epicardial fat depots, which suggested a role for fat depots in the development of the AF substrate., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Aims: Several techniques have been utilized for the ablation of persistent (P) and long-standing persistent (LsP) atrial fibrillation (AF); however, the best approach of substrate ablation remains poorly defined. This study aims to examine the impact of ablation approach on outcomes associated with P or LsP AF ablation by conducting a meta-analysis and regression on contemporary literature., Methods and Results: A systematic literature review was conducted up to 29 July 2015 for scientific literature reporting on outcomes associated with P or LsP AF ablation. One hundred and thirteen studies reported outcomes in a total of 18 657 patients undergoing various ablation approaches for the treatment of P-LsP AF between 2001 and 2015. The point efficacy estimate of a single-AF ablation procedure without the use of anti-arrhythmic drugs was 43% (95% CI; 39-47%). Multiple procedures and/or the use of anti-arrhythmic drugs increase success to 69% (95% CI; 66-71%). Meta-regression revealed that ablation technique (P < 0.001) and left atrial size (P = 0.02) were predictive of single procedure, drug-free success. The addition of extra-pulmonary substrate approaches was associated with declining efficacy when compared to a pulmonary vein ablation alone., Conclusion: The efficacy of a single-AF ablation procedure for P or LsP AF is 43%; however, can be increased to 69% with the use of multiple procedures and/or anti-arrhythmic drugs. Current literature supports the finding that pulmonary vein antrum ablation/isolation is at least equivalently efficacious to other contemporary P-LsP ablation strategies.

Background: Atrial remodeling, vagal tone, and atrial ectopic triggers are suggested to contribute to increased incidence of atrial fibrillation (AF) in endurance athletes. How these parameters change with increased lifetime training hours is debated., Hypothesis: Atrial remodeling occurs in proportion to total training history, thus contributing to elevated risk of AF., Methods: We recruited 99 recreational endurance athletes, subsequently grouped according to lifetime training hours, to undergo evaluation of atrial size, autonomic modulation, and atrial ectopy. Athletes were grouped by self-reported lifetime training hours: low (<3000 h), medium (3000-6000 h), and high (>6000 h). Left atrial (LA) volume, left ventricular (LV) dimensions, and LV systolic and diastolic function were assessed by echocardiography. We used 48-hour ambulatory electrocardiographic monitoring to determine heart rate, heart rate variability, premature atrial contractions, and premature ventricular contractions., Results: LA volume was significantly greater in the high (+5.1 mL/m 2 , 95% CI: 1.3-8.9) and medium (+4.2 mL/m 2 , 95% CI: 0.2-8.1) groups, compared with the low group. LA dilation was observed in 19.4%, 12.9%, and 0% of the high, medium, and low groups, respectively (P = 0.05). No differences were observed between groups for measures of LV dimensions or function. Minimum heart rate, parasympathetic tone expressed using heart rate variability indices, and premature atrial contraction and premature ventricular contraction frequencies did not differ between groups., Conclusions: In recreational endurance athletes, increased lifetime training is associated with LA dilation in the absence of increased vagal parameters or atrial ectopy, which may promote incidence of AF in this cohort., (© 2018 Wiley Periodicals, Inc.)

Aims: To determine stroke risk in subclinical atrial fibrillation (AF) and temporal association between subclinical AF and stroke., Methods and Results: Pubmed/Embase was searched for studies reporting stroke in subclinical AF in patients with cardiac implantable electronic devices (CIEDs). After exclusions, 11 studies were analysed. Of these seven studies reported prevalence of subclinical AF, two studies reported association between subclinical and clinical AF, seven studies reported stroke risk in subclinical AF, and five studies reported temporal relationship between subclinical AF and stroke. Subclinical AF was noted after CIEDs implant in 35% [interquartile range (IQR) 34-42] of unselected patients with pacing indication over 1-2.5 years. The definition and cut-off duration (for stroke risk) of subclinical AF varied across studies. Subclinical AF was strongly associated with clinical AF (OR 5.7, 95% CI 4.0-8.0, P < 0.001, I2 = 0%). The annual stroke rate in patients with subclinical AF > defined cut-off duration was 1.89/100 person-year (95% CI 1.02-3.52) with 2.4-fold (95% CI 1.8-3.3, P < 0.001, I2 = 0%) increased risk of stroke as compared to patients with subclinical AF < cut-off duration (absolute risk was 0.93/100 person-year). Three studies provided mean CHADS2 score. In these studies, with mean CHADS2 score of 2.1 ± 0.1, subclinical AF was associated with annual stroke rate of 2.76/100 person-years (95% CI 1.46-5.23). After excluding patients without AF, only 17% strokes occurred in presence of ongoing AF. Subclinical AF was noted in 29% [IQR 8-57] within 30 days preceding stroke., Conclusion: Subclinical AF strongly predicts clinical AF and is associated with elevated absolute stroke risk albeit lower than risk described for clinical AF.

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome., Methods and Results: We compared obese spontaneously hypertensive rats (SHR-obese, n=7-10) with lean hypertensive controls (SHR-lean, n=7-10) and normotensive rats (n=7-10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR-obese, but not SHR-lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR-lean and SHR-obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P <0.01 for both), but left ventricular end-diastolic pressure was more increased in SHR-obese than in SHR-lean. Impairment of left atrial emptying function, increase in total atrial activation time, and conduction heterogeneity, as well as prolongation of inducible atrial fibrillation durations, were more pronounced in SHR-obese as compared with SHR-lean. Histological and biochemical examinations revealed enhanced triglycerides and more pronounced fibrosis in the left atrium of SHR-obese. Besides increased expression of profibrotic markers in SHR-lean and SHR-obese, the profibrotic extracellular matrix protein osteopontin was highly upregulated only in SHR-obese., Conclusions: In addition to hypertension alone, concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype by impaired left atrial emptying function, local conduction abnormalities, interstitial atrial fibrosis formation, and increased propensity for atrial fibrillation., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: A number of cardiovascular diseases have been linked with bone health and an increased risk of osteoporotic fracture. Whether atrial fibrillation (AF) is associated with subsequent fracture risk is not known., Methods: Administrative, clinical and hospitalisation information were linked over a 14-year period. From this longitudinal, population-based dataset of 113,600 individuals, time-dependent exposures using multivariate Cox proportional hazards regression models were employed to determine incidence rates and hazard ratios (HR) for hip fracture according to a history of AF., Results: The annualised incidence rate for hip fracture was 7.4 per 1000 person-years (95% CI 7.1-7.7) in those without AF and 17.5 per 1000 person-years (95% CI 16.8-18.1) in those with AF. Compared to individuals without AF, those with AF were more likely to develop incident hip fracture in both men (unadjusted HR 2.39 [95% CI 1.96-2.91]) and women (unadjusted HR 2.91 [95% CI 2.55-3.34]). After adjusting for potential confounders, these associations were attenuated but remained statistically significant (adjusted HR 1.97 [95% CI 1.61-2.42] in men; adjusted HR 2.08 [95% CI 1.80-2.39] in women)., Conclusions: A history of AF was associated with an increased risk of hip fracture in this large, population-based analysis. This association appeared to remain significant even after adjusting for potential confounders such as age, comorbidities and medication use. Patients with a history of AF may represent a clinical population in whom screening for and treatment of osteoporosis may be warranted to reduce the risk of subsequent fracture., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recent advances in our understanding of the mechanisms underlying atrial fibrillation (AF) have further underscored the complex pathophysiological basis of the arrhythmia. It has become apparent that the current clinical classification of AF does not reflect the severity of the underlying atrial disease. Atrial fibrosis has been identified as the key structural change in different substrates that are responsible for the perpetuation of AF. Three-dimensional electroanatomical mapping and late gadolinium-enhanced magnetic resonance imaging are novel modalities that can be used to facilitate identification and quantitation of atrial fibrosis for improved delineation of the AF substrate. Advances in AF mapping technology using endocardial 'panaromic' basket-type catheter and non-invasive body surface electrodes have facilitated the identification of two major arrhythmic mechanisms of interest, namely rotational ('rotors') and ectopic focal activations ('foci'). Ongoing research on these potential drivers of AF may provide guidance to more mechanistic based therapies to improve outcomes for this complex arrhythmia in the future. Here, we aim to review the differences in AF substrate in those with paroxysmal and more persistent forms of the arrhythmia by evaluating fibrosis, rotors and foci, towards improved AF substrate classification and individualised substrate based therapies., (Copyright © 2017. Published by Elsevier B.V.)

Atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and mortality worldwide. Management of AF is a complex process involving: 1) the prevention of thromboembolic complications with anticoagulation; 2) rhythm control; and 3) the detection and treatment of underlying heart disease. However, cardiometabolic risk factors, such as obesity, hypertension, diabetes mellitus, and obstructive sleep apnoea, have been proposed as contributors to the expanding epidemic of atrial fibrillation (AF). Thus, a fourth pillar of AF care would include aggressive targeting of interdependent, modifiable cardiovascular risk factors as part of an integrated care model. Such risk factor management could retard and reverse the pathological processes underlying AF and reduce AF burden., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF) imposes a substantial cost burden on the healthcare system. Weight and risk factor management (RFM) reduces AF burden and improves the outcomes of AF ablation., Objectives: This study sought to evaluate the cost and clinical effectiveness of integrating RFM into the overall management of AF., Methods: Of 1,415 consecutive patients with symptomatic AF, 825 patients had body mass index ≥27 kg/m 2 . After screening for exclusion criteria, the final cohort comprised 355 patients: 208 patients who opted for RFM and 147 control subjects and were followed by 3 to 6 monthly clinic review, 7-day Holter monitoring, and AF Symptom Score. A decision analytical model calculated the incremental cost-effectiveness ratios of cost per unit of global well-being gained and unit of AF burden reduced., Results: There were no differences in baseline characteristics or follow-up duration (p = NS). Arrhythmia-free survival was better in the RFM compared with control subjects (Kaplan-Meier: 79% vs. 44%; p < 0.001). At follow-up, RFM group had less unplanned specialist visits (0.19 ± 0.40 vs. 1.94 ± 2.00; p < 0.001), hospitalizations (0.74 ± 1.3 vs. 1.05 ± 1.60; p = 0.03), cardioversions (0.89 ± 1.50 vs. 1.51 ± 2.30; p = 0.002), emergency presentations (0.18 ± 0.50 vs. 0.76 ± 1.20; p < 0.001), and ablation procedures (0.60 ± 0.69 vs. 0.72 ± 0.86; p = 0.03). Antihypertensive (0.53 ± 0.70 vs. 0.78 ± 0.60; p = 0.04) and antiarrhythmic (0.26 ± 0.50 vs. 0.91 ± 0.60; p = 0.003) use declined in RFM. The RFM group had an increase of 0.1930 quality-adjusted life years and a cost saving of $12,094 (incremental cost-effectiveness ratios of $62,653 saved per quality-adjusted life years gained)., Conclusions: A structured physician-directed RFM program is clinically effective and cost saving., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Introduction: Recent research has unravelled an increasing list of cardiac conditions and risk factors that may be responsible for the abnormal underlying atrial substrate that predisposes to atrial fibrillation (AF). Atrial fibrosis has been demonstrated as the pivotal structural abnormality underpinning conduction disturbances that promote AF in different disease models. Despite the advancement in our discoveries of the molecular mechanisms involved in the profibrotic milieu, targeted therapeutics against atrial fibrosis remain lacking. Areas covered: This review is focused on detailing the key molecular signalling pathways that contribute to atrial fibrosis including: angiotensin II, transforming growth factor (TGF- ß1), connective tissue growth factor (CTGF) and endothelin-1. We also discussed the potential therapeutic options that may be useful in modulating the abnormal atrial substrate. In addition, we examined the new paradigm of AF care in lifestyle and risk factor management that has been shown to arrest and reverse the atrial remodelling process leading to improved AF outcomes. Expert commentary: The future of AF care is likely to require an integrated approach consisting of aggressive risk factor management in addition to the established paradigm of rate and rhythm management and anticoagulation. Translational studies on molecular therapeutics to combat atrial fibrosis is urgently needed.

Background: Although adiposity is increasingly recognized as a risk factor for atrial fibrillation (AF), the importance of epicardial fat compared with other adipose tissue depots remains uncertain. We sought to characterize and compare the associations of AF with epicardial fat and measures of abdominal and overall adiposity., Methods and Results: We conducted a meta-analysis of 63 observational studies including 352 275 individuals, comparing AF risk for 1-SD increases in epicardial fat, waist circumference, waist/hip ratio, and body mass index. A 1-SD higher epicardial fat volume was associated with a 2.6-fold higher odds of AF (odds ratio, 2.61; 95% confidence interval [CI], 1.89-3.60), 2.1-fold higher odds of paroxysmal AF (odds ratio, 2.14; 95% CI, 1.45-3.16) and, 5.4-fold higher odds of persistent AF (odds ratio, 5.43; 95% CI, 3.24-9.12) compared with sinus rhythm. Likewise, a 1-SD higher epicardial fat volume was associated with 2.2-fold higher odds of persistent compared with paroxysmal AF (odds ratio, 2.19; 95% CI, 1.66-2.88). Similar associations existed for postablation, postoperative, and postcardioversion AF. In contrast, associations of abdominal and overall adiposity with AF were less extreme, with relative risks per 1-SD higher values of 1.32 (95% CI, 1.25-1.41) for waist circumference, 1.11 (95% CI, 1.08-1.14) for waist/hip ratio, and 1.22 (95% CI, 1.17-1.27) for body mass index., Conclusions: Strong and graded associations were observed between increasing epicardial fat and AF. Moreover, the strength of associations of AF with epicardial fat is greater than for measures of abdominal or overall adiposity. Further studies are needed to assess the mechanisms and clinical relevance of epicardial fat., (© 2016 American Heart Association, Inc.)

Exercise training has considerable health benefits. However, recent research has demonstrated a greater risk of atrial arrhythmias in endurance athletes. The mechanisms promoting atrial fibrillation in athletes are unclear but there seems to be a central role for atrial remodeling, accompanied by autonomic alterations and inflammation. Animal studies have provided unique insights, yet prospective human data are lacking. Treatment options seem to yield similar efficacy to that seen in a nonathletic population and may be justified as an early rhythm control strategy. Further studies are required to enhance understanding of the cardiac adaptations to intensive exercise training., (Copyright © 2016 Elsevier Inc. All rights reserved.)