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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].

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.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 CHAOf 57,056 admitted patients over the study period, 1,210 (2.1%; 46% Indigenous) had a diagnosis of AF. For Indigenous and non-Indigenous individuals45 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. CHAThe 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.

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 ...

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.Administrative, clinical, prescriptive and laboratory data were linked and aggregated over a 12-year period.Single tertiary teaching hospital.19,305 (98%) and 308 (2%) consecutive non-Indigenous and Indigenous Australians with AF identified from administrative databases.Associations of anticoagulation use according to ethnicity.Significant independent predictors of anticoagulation use included hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.17-1.34; p0.001), diabetes (OR 1.14, 95% CI 1.05-1.24; p=0.002), heart failure (OR 1.54 95% CI 1.43-1.66; p0.001) and prior stroke or transient ischaemic attack (OR 2.07, 95% CI 1.84-2.33; p0.001). In contrast, increasing age (OR 0.99, 95% CI 0.98-0.99; p0.001), female gender (OR 0.88, 95% CI 0.82-0.93; p0.001), and vascular disease (OR 0.72, 95% CI 0.64-0.80; p0.001) were significant predictors of no anticoagulation. Hypertension was associated with less anticoagulation use in Indigenous compared to non-Indigenous Australians (p=0.02).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.

Background To evaluate the risk for ventricular arrhythmia (VA) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and determine the prognostic factors. Methods and results PUBMED, EMBASE and SCOPUS were searched up to 14th April 2020. Studies reporting the incidence of SCD, appropriate ICD therapy in CS patients, or relevant prognostic information in patients having undergone MRI, PET, or programmed electrical stimulation (PES) were included. Nineteen studies consisting of 1247 patients, reported the risk of ICD therapies or SCD over a follow-up period of 1.7–7 years. 22.7% (n = 9; 22.7, 95%CI [16.10–29.36]) of patients in primary and 58.4% (n = 9; 58.42, 95% CI [38.61–78.22]) in secondary prevention cohorts experienced appropriate device therapy or SCD events. 18% (n = 2; 18, 95%CI [14–23]) of patients received ≥5 appropriate therapies. 9 out of 664 patients with confirmed cardiac sarcoidosis but without implanted ICDs died suddenly. 17.9% of patients (n = 4; 17.9, 95%CI [10.80–25.03]) experienced inappropriate device therapy. Positive LGE-MRI and PES were associated with an 8.6-fold (n = 6; RR = 8.60, 95%CI [3.80–19.48]) and 9-fold (n = 5; RR = 9.07, 95%CI [4.65–17.68]) increased risk of VA respectively. Positive LGE-MRI and PET with associated with a 6.8-fold (n = 12; RR = 6.82, 95%CI [4.57–10.18]) and 3.4-fold (n = 7; RR = 3.41, 95%CI [2.03–5.74]) respectively for increased risk of major adverse cardiac events. Conclusions The risk of appropriate ICD therapy or sudden cardiac death is high in patients with CS. The presence of LGE-MRI and positive electrophysiology study identify patients at increased risk of ventricular arrhythmias. [CRD42019124220]

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.

Background Anaemia frequently co-exists 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 anaemia 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 anaemia 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 prevalence of anaemia was 16%. Anaemia was associated with a 78% increase in all-cause mortality (HR 1.78, 95% CI 1.44-2.20), 60% increase in cardiovascular mortality (HR 1.60, 95% CI 1.17-2.19), 134% increase in non-cardiovascular 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 Anaemia is a frequently observed comorbidity in patients with AF, and is associated with an increased risk of all-cause, cardiovascular and non-cardiovascular mortality, stroke/systemic thromboembolism, and major and gastrointestinal bleeding. Future studies are required to explore the causes of anaemia in AF, and whether investigation and treatment may be clinically beneficial in affected individuals. This article is protected by copyright. All rights reserved.

Introduction: Amiodarone is a highly effective antiarrhythmic-drug with well recognized toxic side-effects. The effects of the drug late in patients with atrial fibrillation (AF) is not well described. Methods and results: We present a single centre prospectively collected series of patients with thyrotoxicosis occurring late after the cessation of amiodarone. Between 2006 and 2018, 8 patients were identified with amiodarone induced thyrotoxicosis (AIT). Amiodarone was prescribed for AF in 7 patients and ventricular tachycardia in 1 patient. Mean duration of therapy was 329 [42–1092] days, mean dose of 200 ± 103.5 mg/day. Amiodarone use was short term (

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 (I2=37%; P=.11) for falls and moderate bias with low statistical heterogeneity (I2=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.

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.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.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, P0.001), 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.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.

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 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.

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%). APP algorithm reduced premature atrial complexes (PAC) burden (mean difference [MD] –1117.74; 95% CI –1852.36 to –383.11; P = .003; I2 = 67%) but did not decrease AF burden (MD 8.20; 95% CI –5.39 to 21.80; P = .24; I2 = 17%) or AF episodes (MD 0.00; 95% CI –0.24 to 0.25; P = .98; I2 = 0%). Similarly, aATP+APP programming showed no significant difference in AF progression (odds ratio 0.65; 95% CI 0.36–1.14; P = .13; I2 = 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.

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 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)

ObjectiveThe 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.MethodsThe 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.ResultsAF 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; pConclusionsThe 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.

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/m2 and reference: BMI

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/m2. 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.

Funding Acknowledgements Type of funding sources: None. Introduction Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia affecting 1-2% of the global population, with the prevalence of AF increasing dramatically over the past two decades. Although low levels of cardiorespiratory fitness (CRF) and physical activity are predictive of cardiovascular disease onset and mortality, only recently has this emerged as a potential risk factor for AF. Purpose The aim of this meta-analysis was therefore to quantify the relationship between CRF, measured by a symptom limited exercise stress test, and incident AF. We hypothesised that there would be an inverse relationship between CRF and the incidence of AF. Methods The systematic literature review was conducted using PUBMED, MEDLINE and EMBASE databases, with seven studies meeting the inclusion criteria. A random-effects meta-analysis was then used to compare the multivariate risk estimates of the lowest CRF group from each cohort with the group of the highest CRF. Results Data from 206,925 individuals (55.8% males) was used for analysis with a mean age of 55 ± 2.5 years and a mean follow-up period of 10.3 ± 5 years. The total number of AF events across the studies was 19,913. The overall pooled risk of AF in the high-CRF group versus the low-CRF group showed a significant lower risk of incident AF in those with high-CRF (OR: 0.52, 95% CI, 0.44-0.605, p Conclusion There is an inverse association between a lower CRF and an increased risk of AF, with a higher level of CRF protective against AF. This study highlights that low-CRF may be an additional risk factor for AF along with already other established lifestyle-based risk factors such as obesity and hypertension. Exercise interventions should be promoted as a primary prevention strategy in those at risk of developing AF with known risk factors. Future studies are warranted to identify the mechanism(s) through which improved CRF confers a reduction in AF incidence. Abstract Figure. AF risk between high and low-CRF

Funding Acknowledgements Type of funding sources: None. Introduction Atrial fibrillation (AF) is the most common clinically-relevant arrhythmia. Its initiation and maintenance is linked to the presence cardiovascular risk factors such as hypertension and obesity. Higher cardiorespiratory fitness (CRF) has been associated with a better prognosis. However, specific electroanatomical features associated with baseline CRF have not been described. Purpose Compare electroanatomical substrate across exercise capacity levels in patients with AF Methods Patients referred for de novo AF radiofrequency ablation at the Centre for Heart Rhythm Disorders from August 2017 until June 2020 were screened for inclusion and CRF was evaluated in metabolic equivalents (METs) by a symptom-limited maximal treadmill exercise test using the standard Bruce protocol prior to ablation. Predicted CRF was calculated based on established equations and patients were categorized according to the percentage of predicted CRF achieved; low (100%). Total mean and regional peak-to-peak bipolar voltages, percent of low voltage areas (% LVA), conduction velocity (CV) and percent of complex fractionated electrograms (% CFE) in sinus rhythm were compared across groups. Results There were no between-group differences in baseline characteristics, medication use or echocardiographic features. Total mean voltage was significantly lower in the low CRF group compared to both adequate and high CRF. Compared to the high CRF group, roof (3.25 ± 1.2 mV vs 1.9 ± 1.3 mV, p Conclusion Participants in the lower baseline CRF category showed significant reductions in regional voltages along with higher fractionation with preserved conduction velocities. Research on the effect of physical activity and CRF on left atrial arrhythmogenic substrate is required. Abstract Figure. Global and regional mV and % LVA by CRF

Background: Anemia frequently co-exists with atrial fibrillation (AF). We performed a systematic review and meta-analyses to comprehensively assess the effect of anemia on stroke/systemic thromboembolism, bleeding, and mortality in patients with AF. Methods: MEDLINE and Embase were searched until May 2020. Cohort studies and secondary analyses of randomised controlled trials examining the association of anemia with the above outcomes in AF were included and random-effects meta-analyses of reported hazard ratios were undertaken. Results: Twenty-eight studies involving 365,484 patients with mean follow-up of 2.0 years were included. Of the studies that provided the relevant information, 41% of patients were female, mean age was 74.7 years, 76% were on oral anticoagulation, and prevalence of anemia was 16%. Anemia was associated with a 78% increase in all-cause mortality (HR 1.78, 95% CI 1.44-2.20), a 15% increase in stroke/systemic thromboembolism (HR 1.15, 95% CI 1.01-1.31), and a 78% increase in major bleeding (HR 1.78, 95% CI 1.54-2.05). Including studies that reported odds ratios and excluding conference abstracts did not discernibly alter the results. Between-study heterogeneity was substantial in the majority of meta-analyses performed. Additional meta-analyses for cardiovascular/non-cardiovascular mortality and gastrointestinal bleeding as outcomes, and using hemoglobin as a continuous predictor, yielded similar results. Conclusion: Anemia is common in patients with AF and is associated with an increased risk of stroke/systemic thromboembolism, major bleeding, and all-cause mortality. Future studies are required to explore the causes of anemia in AF, and whether further investigation and treatment may be clinically beneficial in affected individuals.

Background There is a growing burden of hospitalizations due to atrial fibrillation (AF). The implications of hospitalisation to the individual with AF has not been well characterized. Purpose To characterise the consequences of presenting to hospital with AF. Methods Individuals presenting to the emergency department (ED) of three hospitals in South Australia from March 2013 to February 2014 with a primary diagnosis of AF were enrolled. Based on coding and individual electronic medical record review all re-presentations over follow up were characterised as: 1) AF related; 2) cardiovascular related (excluding AF); or 3) all other causes. Mortality over follow up was also determined. Results The study cohort comprised of 437 individuals with an AF related index presentation. Mean age was 69±15 years and 49.9% were male. Individuals were followed for a mean of 3.7±0.4 years. There were 2304 unplanned presentations over follow up. The percentage of the study cohort who presented to the ED or were admitted to hospital over follow up is detailed in Figure 1. Compared to individuals who did not have a hospital admission for AF over follow up, those who were readmitted for AF were more likely to be hypertensive (63.2% vs 49.3%, p Conclusions A hospital presentation with a primary diagnosis of AF identifies individuals at high risk of repeat hospitalisations and death. Urgent studies are needed to improve management of this high-risk cohort. Figure 1. Repeat hospital presentations in AF Funding Acknowledgement Type of funding source: None

Background Stroke is one of the most devastating complications of atrial fibrillation (AF) and is associated with poor patient outcomes. Recent registry data has demonstrated improved use of stroke prevention therapy with the advent of direct-acting oral anticoagulants, but little data exists in the Australian health care setting. Purpose To examine the use of oral anticoagulant therapy in a cohort of individuals presenting to the emergency department (ED) due to AF. Methods A total of 437 consecutive individuals who presented to the ED with a primary diagnosis of AF to three tertiary hospitals in our city in South Australia between March 2013 and March 2014 were included. Data were collected retrospectively from electronic medical record review. CHA2DS2-VASc and HAS-BLED scores were calculated and any documented contraindications to the use of oral anticoagulation (OAC) taken in to consideration. Results Mean age was 69±15 years and 49.9% were male. A total of 244 (55.8%) individuals had a prior diagnosis of AF at index presentation. 179 (73.4%) of these individuals recorded a CHA2DS2-VASc score of ≥2. A total of 124 of these individuals were appropriately anticoagulated (69.3%) whilst 37 individuals were not treated with OAC and did not have a documented contraindication (20.7%). Anticoagulation status was unknown in 18 individuals due to a lack of documentation (10.0%). A CHA2DS2-VASc score of 0 was recorded in 25 individuals with a prior diagnosis of AF at index presentation with 3 individuals (12%) inappropriately overtreated with OAC. The remaining 193 individuals (44.2%) presented with a first episode of AF. In 129 (66.8%) of these individuals a CHA2DS2-VASc score of ≥2 was recorded and only 10 individuals had a documented contraindication to the use of OAC. In 119 (61.7%) individuals there were no documented contraindications to the use of OAC. In 74 (62.2%) of these presentations OAC was not commenced, whilst in 45 (37.8%) individuals OAC was prescribed. Conclusions Significant opportunity exists to improve the use of stroke prevention therapy in AF. Despite repeated opportunities to commence this therapy within the hospital setting, it remains frequently underutilised in individuals at high risk of stroke. Funding Acknowledgement Type of funding source: None

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 (VO2peak) 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 VO2peak. RESULTS Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO2peak was 20.3±6.3 mL/kg/min. 24.9% of patients had a VO2peak considered low (

Background Ablation index (AI) and Lesion Size Index (LSI) are novel parameters that incorporates contact force, time, and power in a weighted formula. Recent studies have shown that such indices predict lesion size and durability of pulmonary vein isolation (PVI). However, the outcomes of ablation guided by indices of force-time-power, such as PV reconnections and atrial fibrillation recurrence, have not been well characterised. Objectives To determine the association between indices of force-time-power and acute PV reconnections, procedure and fluoroscopy time and AF recurrence in patients undergoing radiofrequency PVI. Methods PUBMED and EMBASE were searched using the terms "catheter ablation" AND "Ablation index" OR "Contact force" OR "Force time integral" OR "lesion size" from inception through 22 May 2019. Studies reporting the procedure time, ablation time, fluoroscopy time, and incidence of AI acute and late reconnection and AF recurrence were included. Result Six studies were included in this study with 530 patients, which n = 416 were paroxysmal AF and 114 non-paroxysmal AF. All procedural characteristics (procedure, radiofrequency, and fluoroscopy times) were similar between AI guided and non-AI guided ablation (p > 0.05). Two studies comparing mean PV reconnections in AI guided vs. AI Blinded. Two studies compared minimum AI in reconnected vs. non-reconnected PV segments. Acute PV segment reconnection was associated with a lower minimum AI vs. non-reconnection. In 3 studies reporting AI guided vs. AI blinded ablations, AI was associated with an increased freedom from AF after average follow-up of 12 months. Conclusions Radiofrequency ablation guided by AI/LSI was associated with lower acute PV reconnection rates and improved AF freedom after PVI. There was no difference in fluoroscopy, ablation or procedure time with the use of these novel parameters. Abstract Figure.

Funding Acknowledgements Dr Malik is supported by an Australian Postgraduate Award Scholarship from the University of Adelaide. OnBehalf Centre for Heart Rhythm Disorders, University of Adelaide & Royal Adelaide Hospital Background A bi-directional relationship exists between AF and the autonomic nervous system (ANS). Patients with AF studied in sinus rhythm (SR) have impaired vasomotor responses to decreased cardiac volume. Whether autonomic dysfunction worsens during AF itself, is unknown. Purpose We examined haemodynamic responses to lower body negative pressure (LBNP) in patients with persistent AF compared to AF studied in SR. LBNP decreases cardiac volume, deactivates atrial stretch receptors and induces a reflex to maintain blood pressure by increasing systemic vascular resistance (SVR). Methods 21 consecutive patients with paroxysmal or persistent AF were studied; during AF (n = 8) or SR (n = 13). Anti-arrhythmic and anti-hypertensives were withheld for 5 half-lives. Patients underwent LBNP using a custom-made chamber sealing both lower limbs. Negative pressure at sham (-0 mmHg), low (-20 mmHg) and high level (-40 mmHg) was applied for 5 minutes each. Finger photo plethysmography was used for beat-beat-blood pressure. Computation of SVR during AF is not feasible with this method. Therefore, the right forearm was used to perform venous occlusion plethysmography (VOP); non-invasive, well validated with LBNP and impervious to AF: to estimate forearm blood flow (FBF) and SVR (inversely proportional). Results Baseline characteristics and responses to LBNP are presented in Table 1. MAP was maintained, and HR rose slightly, in the SR group. MAP and HR decreased in the AF group. VOP demonstrates a reduction in FBF in the SR group (vasoconstriction); whereas the vasomotor response to LBNP was absent during AF. Figure 1 (Panels A-C). Conclusion The presence of AF is associated with autonomic dysfunction from impaired cardiac volume regulation. This novel finding may contribute to the known risk of falls and syncope due to AF. Further studies are needed to evaluate whether abnormal cardiac reflexes are involved in atrial remodelling and AF progression. Table 1 Baseline Characteristics During AF During SR P Value Age 65 ± 5 59 ± 3 0.4 AAD & Anti-HTN medications withheld (%) 75 85 0.6 Resting mean arterial pressure (MAP) 109 ± 9 93 ± 6 0.1 Resting heart rate (HR) 94 ± 6 60 ± 4 0.0001* Haemodynamic response to LBNP % Δ MAP due to LBNP -9 ± 5 +0.5 ± 3 0.2 % Δ HR due to LBNP -6 ± 3 +5 ± 3 0.03* % Δ FBF due to LBNP +75 ± 59 -27 ± 8 0.02* AAD Anti-arrhthmic. HTN: Hypertension. Mean +/- SEM. Abstract Figure. Vasomotor response to LBNP: in AF vs SR

ObjectiveTo characterise the rate, causes and predictors of cessation of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF).Patients and methodsConsecutive patients with AF with a long-term anticoagulation indication treated with NOACs (dabigatran, apixaban and rivaroxaban) in our centre from September 2010 through December 2016 were included. Prospectively collected data with baseline characteristics, causes of cessation, mean duration-to-cessation and predictors of cessation were analysed.ResultsThe study comprised 1415 consecutive patients with AF, of whom 439 had a CHA2DS2-VASc≥1 and were on a NOAC. Mean age was 71.9±8.7 years and 37% were females. Over a median follow-up of 3.6 years (IQR=2.7–5.3), 147 (33.5%) patients ceased their index-NOAC (113 switched to a different form of OAC), at a rate of 8.8 per 100 patient-years. Serious adverse events warranting NOAC cessation occurred in 28 patients (6.4%) at a rate of 1.6 events per 100 patient-years. The mean duration-to-cessation was 4.9 years (95% CI 4.6 to 5.1) and apixaban had the longest duration-to-cessation with (5.1, 95% CI 4.8 to 5.4) years, compared with dabigatran (4.6, 95% CI 4.2 to 4.9) and rivaroxaban (4.5, 95% CI 3.9 to 5.1), pairwise log-rank p=0.002 and 0.025, respectively. In multivariable analyses, age was an independent predictor of index-NOAC cessation (HR 1.03, 95% CI 1.01 to 1.05; p=0.006). Female gender (HR 2.2, 95% CI 1.04 to 4.64; p=0.04) independently predicted serious adverse events.ConclusionIn this ‘real world’ cohort, NOAC use is safe and well-tolerated when prescribed in an integrated care clinic. Whether apixaban is better tolerated compared with other NOACs warrants further study.

Background: Dermatophytosis is a superficial fungal infection that has high affinity for keratinized tissues of the body. The treatment of localized dermatophytosis is a major concern for the dermatologist especially in tropical countries like India. Various topical antifungals are available for the treatment of localized uncomplicated dermatophytosis. Luliconazole is an azole antifungal available that has potent activity against dermatophytes. Objectives: The objective of this study was to compare two treatment modalities for the treatment of localized dermatophytosis in terms of efficacy, safety, and cost evaluation. Materials and Methods: This was a prospective and observational study carried out for 6 months and included 200 patients (luliconazole group [n = 94] and clotrimazole group [n = 106]). Patients were followed up for 2, 4, and 6 weeks. Outcome parameters such as pruritis, erythema, scaling, vesiculations, and global assessment score were noted at 2, 4, and 6 weeks for the assessment of efficacy. The statistical analysis was done using Chi-square and Student's t-test. Results: Luliconazole and clotrimazole showed 56.38% and 23.58% cure rate at the end of two weeks respectively (P < 0.05). At the end of treatment, the cure rates were 98.93% and 95.28% in luliconazole and clotrimazole, respectively (P > 0.005). Both the drugs were equally safe. On cost-effective analysis, luliconazole was found to be more cost-effective than clotrimazole at the end of 2 weeks. Conclusion: Therapeutic efficacy of luliconazole was more as significant proportion of patients achieved complete clearance of lesions at faster rate within 2 weeks with convenient once daily application.

Background Research links blood pressure variability ( BPV ) with stroke; however, the association with cerebral small‐vessel disease ( CSVD ) remains unclear. As BPV and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding cerebrovascular morphological characteristics. Methods and Results A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (BPV quantified by any metric over any duration; comparison, (1) low versus high or mean BPV and (2) people with versus without CSVD ; and outcomes, (1) CSVD as subcortical infarct, lacunae, white matter hyperintensities, cerebral microbleeds, or enlarged perivascular spaces; and (2) standardized mean difference in BPV . A total of 27 articles were meta‐analyzed, comprising 12 309 unique brain scans. A total of 31 odds ratios ( OR s) were pooled, indicating that higher systolic BPV was associated with higher odds for CSVD ( OR, 1.27; 95% CI, 1.14–1.42; I 2 =85%) independent of mean systolic pressure. Likewise, higher diastolic BPV was associated with higher odds for CSVD ( OR, 1.30; 95% CI, 1.14–1.48; I 2 =53%) independent of mean diastolic pressure. There was no evidence of a pairwise interaction between systolic/diastolic and BPV /mean OR s ( P =0.47), nor a difference between BPV versus mean pressure OR s ( P =0.58). Fifty‐four standardized mean differences were pooled and provided similar results for pairwise interaction ( P =0.38) and difference between standardized mean differences ( P =0.70). Conclusions On the basis of the available studies, BPV was associated with CSVD independent of mean blood pressure. However, more high‐quality longitudinal data are required to elucidate whether BPV contributes unique variance to CSVD morphological characteristics.

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 (

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 (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.

To determine stroke risk in subclinical atrial fibrillation (AF) and temporal association between subclinical AF and stroke.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.Subclinical AF strongly predicts clinical AF and is associated with elevated absolute stroke risk albeit lower than risk described for clinical AF.

Postural tachycardia syndrome (POTS) is the combination of an exaggerated heart rate response to standing, in association with symptoms of lightheadedness or pre-syncope that improve when recumbent. The condition is often associated with fatigue and brain fog, resulting in significant disruptions at a critical time of diagnosis in adolescence and young adulthood. The heterogeneity of the underlying pathophysiology and the variable response to therapeutic interventions make management of this condition challenging for both patients and physicians alike. Here, we aim to review the factors and mechanisms that may contribute to the symptoms and signs of POTS and to present our perspectives on the clinical approach toward the diagnosis and management of this complex syndrome.

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.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, p0.001). 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).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.

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.

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.

BACKGROUND Medical technology has made significant advances over the last few decades with smaller and more dynamic pacemakers. However, technical failures leading to premature replacement is a cause of concern. We present a series of Medtronic EnRhythm devices that reached premature elective replacement indicator (ERI). METHODS The database of Centre of Heart Rhythm Disorders was searched for EnRhythm device implantation from 2006 to 2011. Battery depletion

Background Implantation of implantable cardioverter defibrillator (ICD) is a Class IIb indication in patients with Cardiac Sarcoid and with LVEF 36%-49% despite immunosuppression and optimal heart failure therapy. Purpose This systematic review and meta-analysis aimed to provide an estimate on the incidence of ventricular arrhythmias and risk of sudden cardiac death (SCD) in patients with CS. Methods The terms “Cardiac Sarcoidosis*” AND “Implantable Cardioverter Defibrillator” AND “Sudden Cardiac Death” were searched on PubMed, EMBASE, and Scopus on 21st of September 2018 yielding 759 articles. After exclusions, 12 studies met inclusion criteria. Results The 12 studies consisted of 612 patients with CS of which 534 had ICD implanted for primary or secondary prevention. Assuming appropriate device therapy as a surrogate for SCD, the annual incidence of appropriate ICD therapies and SCD combined was 6.3% (95% CI; 3.5%-9.1%) in primary prevention cohorts, 11.6% (95% CI; 7.8%-15.3%) in secondary prevention cohorts, and 8.7% (95% CI; 6.0%-11.5%) in both cohorts. The mean left ventricular ejection fraction (LVEF) was pooled as 59±7 (n=155) in primary prevention cohorts and 48±15 (n=48) in secondary prevention cohorts. However, the LVEF was 35±13 (n=28) in those with appropriate ICD therapy, and 49±16 (n=47) in those with ICDs without therapy. Incidence of SCD in Combined Cohorts Conclusion The incidence of ventricular arrhythmias and SCD is high not only secondary but also in primary prevention cohorts of CS. This data supports the role of implanting ICDs for primary prevention in patients with CS with mild to moderate reduction in LVEF. Acknowledgement/Funding None

Background Obesity-mediated epicardial adipose tissue (EAT) expansion drives fat cell infiltration which forms the unique substrate for atrial fibrillation (AF). The LEGACY study showed the benefits of weight loss but an attenuated response with weight fluctuation. How fluxes in weight impacts the atrial substrate in not known. Objective To investigate EAT and the atrial substrates due to weight fluctuation, with comparison to stable obesity. Methods We studied 24 sheep in 3 equal groups over 80 weeks: 1. Obesity induced by high calorie diet fed ad libitum; 2. Weight fluctuation induced by 20-week cycle of weight gain/loss (20:20:20:20); and 3. Lean controls fed quality hay to maintain baseline weight. All sheep underwent: daily weight measurement; haemodynamic and imaging assessments (cardiac MRI; dual-energy X-ray absorptiometry; and matrix assisted laser desorption infrared lipid imaging); electrophysiological studies and electroanatomic mapping; histological and structural analysis. Evaluations included: atrial voltage, conduction velocity, and refractoriness (7 sites, 2 cycle lengths), electrogram fractionation, EAT volume, fibro-fatty infiltration, myolysis of myocytes, and spatial distribution of intra-atrial lipids. Results The Table shows the group differences. Compared to reference controls, obesity demonstrated: Increased atrial volume and pressure, abnormal atrial electrical properties, expanded EAT and ensuing fibro-fatty infiltrations, and myolysis of myocytes. Despite comparable weight and EAT with controls, weight fluctuation resulted in extensive and severe fibro-fatty infiltrations, and twofold greater myolysis that persisted. Moreover, characteristic profiles and abundance of lipid species in the atrial myocardium were noted on further evaluation. More importantly, EAT and fibro-fatty infiltrates strongly correlated with increased atrial volume and pressure; with only fibro-fatty infiltrates correlating with fractionated electrograms (r=0.71, p Conclusions Obesity induces fibro-fatty replacement of atrial myocytes and deterioration of contractile units, which may drive impaired electrical remodeling. Despite final weight loss, weight fluctuation demonstrates residual electro-structural, fibro-fatty and contractile substrates.

Introduction Obesity and enhanced inflammatory response are two independent risk factors involved in the pathogenesis of atrial fibrillation (AF). Components of the NLRP3 inflammasome have been found to be expressed in cardiomyocytes and cardiac fibroblasts and that increased inflammasome activation contributes to the pathogenesis of AF. The NLRP3 inflammasome is a multi-protein signaling complex that is activated in two steps: 1st) a priming event that includes a NFκB-activating stimuli which increases the expression of pro-inflammatory cytokines, and 2nd) a triggering event that includes the assembly of the inflammasome complex and activation of caspase-1 which promotes the production of pro-inflammatory cytokines like interleukin 1 beta (IL-1b). Purpose We used a sheep model of sustained obesity to characterize the association between atrial myocardial fat infiltration, atrial activation of the NLRP3 inflammasome and the development of an atrial arrhythmogenic substrate for AF. Methods Eight sheep were fed ad libitum calorie-dense diet over 40 weeks to gain weight and were maintained in this state of sustained obesity for another 40 weeks. Eight lean, weight-controlled and aged-matched sheep served as control. Atrial fat infiltration was determined by oil-red staining and NLRP3 inflammasome activation was assessed by immunoblot in atrial whole-tissue lysate. Atrial effective refractory periods (aERPs) were evaluated (twice diastolic threshold, cycle length (CL) of 400 ms, S1S2 -protocol). Results Sustained obesity was associated with increased atrial fat infiltration (lean: 0.8±0.3% vs. obese: 2.3±1.2%, p=0.1) and shorter aERP (lean: 169±22ms vs. obese: 138±26ms, p=0.03). Protein levels of caspase-1 and mature IL-1β were significantly enhanced (p=0.04 and p=0.01, respectively). Further shortening of aERP correlated with increasing atrial protein levels of caspase-1 (r=0.59, p=0.02). In contrast, levels of TNFα and NFκB were not significantly changed in atria of sheep with sustained obesity. Conclusions Sustained obesity is associated with increased expression of NLRP3 inflammasome-related proteins and the development of an arrhythmogenic substrate for AF. Our study suggest that the increased activity is due to increased triggering, rather than increased gene transcription. Whether NLRP3 inflammasome activation represents a modifiable target to prevent AF in obesity warrants further study.

Background Sleep-disordered breathing (SDB) is an important risk factor for developing atrial fibrillation (AF), and treatment of concomitant SDB can improve AF rhythm outcomes. Diagnosis of SDB requires sleep studies which can pose a significant time and resource burden. We sought to develop a prediction score based on clinical characteristics that can help identify AF patients who require further assessment for SDB. Methods Prospectively-collected data for 442 consecutive patients treated for AF from 2009 to 2017 were analysed. All patients were considered candidates for rhythm-control and therefore referred for sleep studies. The diagnosis of SDB was confirmed using in-lab polysomnography and classified using the apnoea-hypopnoea-index (AHI), with cut-offs of ≥15/hr and ≥30/hr indicating moderate-to-severe and severe SDB respectively. Patients treated up to 2015 formed the derivation cohort (n=311) and the remainder (n=113) formed the validation cohort. Multivariate logistic regression analysis was used to identify clinical variables predictive of moderate-to-severe SDB. A risk score model was developed based on regression coefficients and tested using receiver-operating-characteristics analyses on the validation cohort. Results Overall, mean age was 60±11 years, mean body mass index (BMI) was 30±5 kg/m2 and 69% were men. The prevalence of moderate-to-severe SDB was 33.7%. There were no significant differences in baseline characteristics between the derivation and validation cohorts. Male gender (score=1), overweight (BMI: 25–29 kg/m2, score=2), obesity (BMI≥30 kg/m2, score=3), diabetes (score=1), and stroke (score=2) were significantly independently predictive of moderate-to-severe SDB and formulated the score. The score performed well to predict moderate-to-severe SDB with a C-statistic of 0.73 (95% CI: 0.67–0.79, P Sensitivity and specificity table Conclusion A novel risk score comprising clinical characteristics can identify patients with AF likely to benefit from further assessment for SDB. Application of this model may aid optimise resource utilisation and facilitate timely patient care.

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.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.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, p0.001), Indigenous Australians had greater valvular heart disease, diabetes, and alcohol excess compared to non-Indigenous Australians (p0.05 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 (p0.05 for all). Valvular heart disease remained a significant predictor of poorer TTR in multivariate analyses (p=0.004).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.

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.

ObjectiveThe aim of the meta-analysis was to determine the association of obesity and heart failure (HF) and the cardiac impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obese subjects.MethodsMEDLINE, Embase and Web of Science were searched up to 3 April 2018. Studies reporting association and prognostic impact of obesity in HF and the impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obesity were included in the meta-analysis.Results4959 citations were reviewed. After exclusions, 29 studies were analysed. A ‘J curve’ relationship was observed between body mass index (BMI) and risk of HF with maximum risk in the morbidly obese (1.73 (95% CI 1.30 to 2.31), pConclusionsDespite the increased risk of HF with obesity, an ‘obesity paradox’ is observed for all-cause mortality. However, the nadir for CV mortality is observed in the overweight group. Importantly, intentional weight loss was associated with improvement in indices of cardiac structure and myocardial function in obese patients.Trial registration numberAPP 74412.

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.

Background: Sequentially mapped complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) sites have been targeted during catheter ablation for atrial fibrillation (AF). However, these strategies have yielded variable success and have not been shown to correlate consistently with AF dynamics. Here, we evaluated whether the spatiotemporal stability of CFAE and DF may be a better marker of AF sustenance and termination. Methods: Eighteen sheep with 12 weeks of “one-kidney, one-clip” hypertension underwent open-chest studies. A total of 42 self-terminating (28–100 s) and 6 sustained (>15 min) AF episodes were mapped using a custom epicardial plaque and analyzed in 4-s epochs for CFAE, using the NavX CFE-m algorithm, and DF, using a Fast Fourier Transform. The spatiotemporal stability index (STSI) was calculated using the intraclass correlation coefficient of consecutive AF epochs. Results: A total of 67,733 AF epochs were analyzed. During AF initiation, mean CFE-m and the STSI of CFE-m/DF were similar between sustained and self-terminating episodes, although median DF was higher in sustained AF (p=0.001). During sustained AF, the STSI of CFE-m increased significantly (p=0.02), whereas mean CFE-m (p=0.5), median DF (p=0.07), and the STSI of DF remained unchanged (p=0.5). Prior to AF termination, the STSI of CFE-m was significantly lower (p