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Aims There is a paucity of epidemiological evidence on alcohol and the risk of bradyarrhythmias. We thus characterized associations of total and beverage-specific alcohol consumption with incident bradyarrhythmias using data from the UK Biobank. Methods and results Alcohol consumption reported at baseline was calculated as UK standard drinks (8 g alcohol)/week. Bradyarrhythmia events were defined as sinus node dysfunction (SND), high-level atrioventricular block (AVB), and permanent pacemaker implantations. Outcomes were assessed through hospitalization and death records, and dose–response associations were characterized using Cox regression models with correction for regression dilution bias. We studied 407 948 middle-aged individuals (52.4% female). Over a median follow-up time of 11.5 years, a total of 8 344 incident bradyarrhythmia events occurred. Increasing total alcohol consumption was not associated with an increased risk of bradyarrhythmias. Beer and cider intake were associated with increased bradyarrhythmia risk up to 12 drinks/week; however, no significant associations were observed with red wine, white wine, or spirit intake. When bradyarrhythmia outcomes were analysed separately, a negative curvilinear was observed for total alcohol consumption and risk of SND, but no clear association with AVB was observed. Conclusion In this predominantly White British cohort, increasing total alcohol consumption was not associated with an increased risk of bradyarrhythmias. Associations appeared to vary according to the type of alcoholic beverage and between different types of bradyarrhythmias. Further epidemiological and experimental studies are required to clarify these findings.

Although previous studies have demonstrated a U-shaped relationship between alcohol and sudden cardiac death (SCD), there is a paucity of evidence on the role of alcohol specifically on incident ventricular arrhythmias (VAs).The purpose of this study was to characterize associations of total and beverage-specific alcohol consumption with incident VA and SCD using data from the UK Biobank.Alcohol consumption reported at baseline was calculated as UK standard drinks (8 g of alcohol) per week. Outcomes were assessed through hospitalization and death records. Alcohol consumption was modeled as restricted cubic splines in multivariate Cox regression models and corrected for regression dilution bias.We studied 408,712 middle-aged individuals (52.1% female) over a median follow-up time of 11.5 years. A total of 1733 incident VA events and 2044 SCDs occurred. For incident VA, no clear association was seen with total alcohol consumption. Although consumption of greater amounts of spirits was associated with increased VA risk, no other significant beverage-specific associations were observed. For SCD, a U-shaped association was seen for total alcohol consumption, such that consumption of26 drinks per week was associated with lowest risk. Consumption of greater amounts of beer, cider, and spirits was potentially associated with increasing SCD risk, whereas increasing red and white wine intake was associated with reduced risk.In this predominantly white cohort, no association of total alcohol consumption was observed with VA, whereas a U-shaped association was present for SCD. Additional studies utilizing accurately defined VA and SCD events are required to provide further insights into these contrasting findings.

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.

The global prevalence of atrial fibrillation (AF) has increased substantially over the past three decades and is currently approximately 60 million cases. Incident AF and its clinical consequences are largely the result of risk factors that can be modified by lifestyle changes. In this Review, we provide evidence that the lifetime risk of AF is modified not only by sex and race but also through the clinical risk factor and comorbidity burden of individual patients. We begin by summarizing the epidemiology of AF, focusing on non-modifiable and modifiable risk factors, as well as targets and strategies for the primary prevention of AF. Furthermore, we evaluate the role of modifiable risk factors in the secondary prevention of AF as well as the potential effects of risk factor interventions on the frequency and severity of subsequent AF episodes. We end the Review by proposing strategies that require evaluation as well as global policy changes that are needed for the prevention of incident AF and the management of recurrent episodes in patients already affected by AF.

Heart rate reserve (HRR) is used to guide exercise training in patients with cardiovascular disease, primarily as a surrogate for oxygen uptake reserve (VOinf2/infR) as a marker of metabolic demand. However, the relationship between HRR and VOinf2/infR in patients with atrial fibrillation (AF) is not well described. We aimed to assess the validity of HRR as a surrogate for VOinf2/infR to guide exercise intensity in AF patients.One hundred one patients with non-permanent AF undertaking a cardiopulmonary exercise test (CPET) were prospectively enrolled. HR and VOinf2/infvalues were recorded throughout exercise to determine HRR and VOinf2/infR at each workload. Linear regression was used to calculate the slope and y-intercept for HRR versus VOinf2/infR 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-VOinf2/infR relationship was also assessed.The slope of HRR-VOinf2/infR 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, P0.001). The mean y-intercept slope was 20.1±41.6, differing significantly from 0 (mean difference: 20.1, 95% CI: 11.9-28.3, P0.001). The presence of AF during CPET, beta-blockers or chronotropic incompetence did not independently alter the association between VOinf2/infR and HRR.HRR is not equivalent to VOinf2/infR 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-VOinf2/infR relationship.

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.

Background Atrial fibrillation (AF) impacts performance and horse and jockey safety. Understanding the outcomes of AF identified postrace will better inform regulatory policy. Hypothesis/objectives To investigate the outcomes after episodes of AF identified postrace and determine whether affected horses are at increased risk of additional episodes compared to the general racing population. Animals Total of 4684 Thoroughbred racehorses. Methods Race records for Thoroughbred horses racing in Hong Kong from 2007 to 2017 were reviewed. Horses that performed below expectation were examined by cardiac auscultation and ECG. Incidence and recurrence of AF were compared between horses with and without a history of AF and between horses with paroxysmal and persistent episodes using Fisher's exact test. Results There were 96 135 race starts during the study. Atrial fibrillation was identified in 4.9% of horses, with an overall incidence of 2.7 episodes per 1000 starts. The incidence of AF in horses after any previous episode (12.8 per 1000 starts) was higher than for horses with no previous episode (2.4 per 1000 starts; odds ratio [OR], 5.3; 95% confidence interval [CI], 3.8-7.6). Recurrence was seen in 64% of horses previously treated for persistent AF, which was higher than recurrence in horses with paroxysmal AF (23%; OR, 5.9; 95% CI, 1.6-21.2). Median duration between episodes was 343 days (range, 34-1065). Conclusions and clinical importance Thoroughbreds are at increased risk of recurrent AF after both paroxysmal and persistent episodes, but the duration of time between episodes varies widely. These findings support a substantial burden of AF among individual Thoroughbred racehorses.

Aims Our objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19. Methods and results In this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54–0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58–0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56–0.85, P < 0.001). Conclusions During COVID-19, there was a 32% reduction in ventricular arrhythmias needing device therapies, coinciding with measures of social isolation. There was a 39% reduction in the proportion of patients with ventricular arrhythmias in states with higher COVID-19 incidence. These findings highlight the potential role of real-life stressors in ventricular arrhythmia burden in individuals with ICDs. Trial registration Australian New Zealand Clinical Trial Registry; URL: https://www.anzctr.org.au/; Unique Identifier: ACTRN12620000641998, Graphical Abstract

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.

AliveCor is a smartphone electrocardiography device (iECG) providing automated heart rate (HR) and rhythm determination. Atrial fibrillation (AF) in horses often is paroxysmal and rapid ECG acquisition is needed for diagnostic confirmation. iECGs were collected post-race from 15 horses with AF and 64 horses in sinus rhythm (SR). Results of manual assessment were compared to 3 commercial algorithms for HR and rhythm. Agreement between manually derived HR (HRM ) and HR derived by the AliveECG Vet (HRVET ) and Kardia version-1 (KV1 HR) and Kardia advanced (KADV HR) algorithms was quantified by the Bland-Altman limits of agreement test. Agreement between manual rhythm classification and KV1 and KADV algorithms for AF and SR was calculated by the Kappa statistical coefficient. The agreement (bias, 95% limits), between HRM and HRVET was 7.1 BPM (-29 to 43) in AF and -4.2 BPM (-38 to 30) in SR, between HRM and KV1 HR, was -0.3 BPM (-31 to 30) in AF and 0.2 BPM (-3 to 4) in SR, and between HRM and KADV HR was 7.0 BPM (-29 to 43) in AF and 0.2 BPM (-3.9 to 4.2) in SR. Agreement between manual rhythm classification and KV1 was 0.36 (0.13-0.59), and KADV was 0.84 (0.68-0.99). Sensitivity and specificity for identification of AF and SR of the KV1 algorithm were 60, 100% and 83, 100%, respectively, and of KADV was 87, 100% and 93, 100% respectively. The Kardia algorithms improved precision for HR determination in SR but not AF. The advanced algorithm accurately distinguished between AF and SR. The iECG is suitable for recording episodes of AF following exercise.

Aims The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF). Methods and results A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18–1.31)]. This effect was modified by overall level of activity (P, Graphical Abstract

In this study, we sought to estimate the prevalence of concomitant sleep-disordered breathing (SDB) in patients with atrial fibrillation (AF) and to systematically evaluate how SDB is assessed in this population.We searched Medline, Embase and Cinahl databases through August 2020 for studies reporting on SDB in a minimum 100 patients with AF. For quantitative analysis, studies were required to have systematically assessed for SDB in consecutive AF patients. Pooled prevalence estimates were calculated with the use of the random effects model. Weighted mean differences and odds ratios were calculated when possible to assess the strength of association between baseline characteristics and SDB.The search yielded 2758 records, of which 33 studies (n = 23,894 patients) met the inclusion criteria for qualitative synthesis and 13 studies (n = 2660 patients) met the meta-analysis criteria. The pooled SDB prevalence based on an SDB diagnosis cutoff of apnea-hypopnea index (AHI) ≥ 5/h was 78% (95% confidence interval [CI] 70%-86%; P0.001). For moderate-to-severe SDB (AHI ≥ 15/h), the pooled SDB prevalence was 40% (95% CI 32%-48%; P0.001). High degrees of heterogeneity were observed (ISDB is highly prevalent in patients with AF. Wide variation exists in the diagnostic tools and thresholds used to detect concomitant SDB in AF. Prospective systematic testing for SDB in unselected cohorts of AF patients may be required to define the true prevalence of SDB in this population.

Aims Physical activity reduces cardiovascular disease burden and mortality, although its relationship with cardiac arrhythmias is less certain. The aim of this study was to assess the association between self-reported physical activity and atrial fibrillation (AF), ventricular arrhythmias and bradyarrhythmias, across the UK Biobank cohort. Methods and results We included 402 406 individuals (52.5% female), aged 40–69 years, with over 2.8 million person-years of follow-up who underwent self-reported physical activity assessment computed in metabolic equivalent-minutes per week (MET-min/wk) at baseline, detailed physical assessment and medical history evaluation. Arrhythmia episodes were diagnosed through hospital admissions and death reports. Incident AF risk was lower amongst physically active participants, with a more pronounced reduction amongst female participants [hazard ratio (HR) for 1500 vs. 0 MET-min/wk: 0.85, 95% confidence interval (CI) 0.74–0.98] than males (HR for 1500 vs. 0 MET-min/wk: 0.90, 95% CI 0.82–1.0). Similarly, we observed a significantly lower risk of ventricular arrhythmias amongst physically active participants (HR for 1500 MET-min/wk 0.78, 95% CI 0.64–0.96) that remained relatively stable over a broad range of physical activity levels between 0 and 2500 MET-min/wk. A lower AF risk amongst female participants who engaged in moderate levels of vigorous physical activity was observed (up to 2500 MET-min/wk). Vigorous physical activity was also associated with reduced ventricular arrhythmia risk. Total or vigorous physical activity was not associated with bradyarrhythmias. Conclusion The risk of AF and ventricular arrhythmias is lower amongst physically active individuals. These findings provide observational support that physical activity is associated with reduced risk of atrial and ventricular arrhythmias.

Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening.

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.

Atrial fibrillation is the most common sustained arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system has a significant role in the milieu predisposing to the triggers, perpetuators and substrate for atrial fibrillation. It has direct electrophysiological effects and causes alterations in atrial structure. In a significant portion of patients with atrial fibrillation, the autonomic nervous system activity is likely a composite of reflex excitation due to atrial fibrillation itself and contribution of concomitant risk factors such as hypertension, obesity and sleep-disordered breathing. We review the role of autonomic nervous system activation, with focus on changes in reflex control during atrial fibrillation and the role of combined sympatho-vagal activation for atrial fibrillation initiation, maintenance and progression. Finally, we discuss the potential impact of combined aggressive risk factor management as a strategy to modify the autonomic nervous system in patients with atrial fibrillation and to reverse the arrhythmogenic substrate. (c) 2018 Elsevier B.V. All rights reserved.

Visual Abstract, Highlights • The role of the protease cathepsin A for the progression of left ventricular remote remodeling and atrial cardiomyopathy in ischemic cardiomyopathy is unknown. • In rats with ventricular ischemia and reperfusion, cathepsin A is up-regulated in the left ventricular and atrial tissue remote from the infarcted area. • Pharmacological inhibition of cathepsin A protease activity by SAR significantly reduces remote ventricular remodeling and atrial extracellular matrix remodeling, represented by fibrosis formation and connexin 43 lateralization. • Prevention of ventricular remote remodeling and atrial cardiomyopathy by SAR increased ventricular viable myocardium and atrial emptying function reducing susceptibility to atrial fibrillation. • Remote ventricular and atrial extracellular matrix remodeling may represent a promising target for pharmacological atrial fibrillation upstream therapy following myocardial infarction., Summary After myocardial infarction, remote ventricular remodeling and atrial cardiomyopathy progress despite successful revascularization. In a rat model of ventricular ischemia/reperfusion, pharmacological inhibition of the protease activity of cathepsin A initiated at the time point of reperfusion prevented extracellular matrix remodeling in the atrium and the ventricle remote from the infarcted area. This scenario was associated with preservation of more viable ventricular myocardium and the prevention of an arrhythmogenic and functional substrate for atrial fibrillation. Remote ventricular extracellular matrix remodeling and atrial cardiomyopathy may represent a promising target for pharmacological atrial fibrillation upstream therapy following myocardial infarction.

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.

Chronological aging is one of the major risk factors of cardiovascular (CV) disease (CVD); however, the effect of biological aging on CVD and outcomes remain poorly understood. Herein, we evaluated the association between leukocyte telomere length (LTL), a marker of biological age, and CV outcomes.We searched PubMed, Embase, Ovid Medline, and Web of Science Core Collection for the studies on the association between LTL and myocardial infarction (MI), CV death, and/or CVD risk factors from inception to July 2020. Extracted data were pooled in a random-effects meta-analysis and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI) per LTL tertile.A total of 32 studies (n = 144,610 participants) were included. In a pooled analysis of MI and LTL in a multivariate-adjusted model, the shortest LTL was associated with a 39% higher risk of MI (RR, 1.39; 95% CI, 1.16-1.67; P0.001). After adjusting for chronological age and traditional covariance, we showed a 28% increased risk of CV death in the shortest tertile of LTL (RR, 1.28; 95% CI, 1.05-1.56; P = 0.01). Analysis of the studies that investigated the association between CV risk factors and LTL (n = 7) showed that diabetes mellitus is associated with a 46% increased risk of LTL attrition (RR, 1.46; 95% CI, 1.46-2.09; P = 0.039).This study shows a strong association between LTL, a marker of biological aging, and the risk of MI and CV death. Cardiometabolic risk factors contribute to telomere attrition and therefore accelerates biological aging.

This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF).Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown.Individuals with nonpermanent AF (n = 48) were prospectively studied (23 in the in-AF group and 25 in sinus rhythm [SR]) with 12 matched control subjects. We performed: 1) low-level lower body negative pressure (LBNP), which decreases cardiac volume, offloading predominantly cardiac afferent (volume-sensitive) low-pressure baroreceptors; 2) Valsalva reflex (predominantly arterial high-pressure baroreceptors); and 3) isometric handgrip reflex (both baroreceptors). We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR). LBNP elicits reflex vasoconstriction, estimated using venous occlusion plethysmography-derived forearm blood flow (∝1/vascular resistance), maintaining MAP. To assess reversibility, we repeated LBNP (same day) after 1-hour low-level tragus stimulation (in n = 5 in the in-AF group and n = 10 in the in-SR group) and6 weeks post-cardioversion (n = 7).The 3 groups were well matched for age (59 ± 12 years, 83% male), body mass index, and risk factors (P = NS). The in-AF group had higher left atrial volume (P 0.001) and resting HR (P = 0.01) but similar MAP (P = 0.7). The normal LBNP vasoconstriction (-49 ± 5%) maintaining MAP (control subjects) was attenuated in the in-SR group (-12 ± 9%; P = 0.005) and dysfunctional in the in-AF group (+11 ± 6%; P 0.001), in which MAP decreased and HR was unchanged. Valsalva was normal throughout. Handgrip MAP response was lowest in the in-AF group (P = 0.01). Interestingly, low-level tragus stimulation and cardioversion improved LBNP vasoconstriction (-48 ± 15%; P = 0.04; and -32 ± 9%; P = 0.02, respectively).Cardiac afferent (volume-sensitive) reflexes are abnormal in AF patients during SR and dysfunctional during AF. This could contribute to AF progression, thus explaining "AF begets AF." (Characterisation of Autonomic function in Atrial Fibrillation [AF-AF Study]; ACTRN12619000186156).

Aims The aim of this study is to determine the association between the coronavirus disease 2019 (COVID-19) pandemic and atrial fibrillation (AF) occurrence in individuals with cardiac implantable electronic devices (CIEDs). Method and results Multi-centre, observational, cohort study over a 100-day period during the COVID-19 pandemic (COVID-19) in the USA. Remote monitoring was used to assess AF episodes in patients with a CIED (pacemaker or defibrillator; 20 centres, 13 states). For comparison, the identical 100-day period in 2019 was used (Control). The primary outcomes were the AF burden during the COVID-19 pandemic, and the association of the pandemic with AF occurrence, as compared with 1 year prior. The secondary outcome was the association of AF occurrence with per-state COVID-19 prevalence. During COVID-19, 10 346 CIEDs with an atrial lead were monitored. There were 16 570 AF episodes of ≥6 min transmitted (16 events per 1000 patient days) with a significant increase in proportion of patients with AF episodes in high COVID-19 prevalence states compared with low prevalence states [odds ratio 1.34, 95% confidence interval (CI) 1.21–1.48, P, Graphical Abstract Graphical Abstract

To summarize the evidence underpinning the role of risk factor management in atrial fibrillation (AF) and to describe the key components critical to the successful delivery of this aspect of AF care. Recent studies exploring the role of risk factor management in AF have demonstrated the importance of comprehensively and simultaneously managing all risk factors. Strong evidence exists to support the aggressive management of overweight and obesity, hypertension, diabetes, obstructive sleep apnea, alcohol excess, and physical inactivity in improving outcomes in this population. Other factors, such as dyslipidemia, are managed according to individual cardiovascular risk. The use of protocol-driven care, assisted by a checklist, is critical to ensure that all risk factors are comprehensively addressed in a standardized fashion. Engaging the patient through the health behavior change process, by assessing importance and confidence in achieving the desired change and goal setting to achieve targets, increases the likelihood of success. Regular reviews and feedback are essential to ensure accountability and ongoing engagement. Risk factor management is an essential pillar of AF care that should be incorporated alongside appropriate use of oral anticoagulation, rate control, and rhythm management. Successful implementation of this aspect of comprehensive AF management requires a protocol-driven approach with regular follow-up to maximize patient engagement.

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

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is the most common clinically relevant arrhythmia, and its occurrence is associated with pathological left atrial (LA) remodelling. In these patients, low cardiorespiratory fitness (CRF) is associated with increased AF recurrence. Speckle tracking derived LA strain (LAS) permits chamber function quantification and provides angle-independent and highly reproducible measurements of chamber deformation. However, the relationship between CRF and LA function, amongst AF patients is poorly understood. Purpose To compare LA function amongst AF patients stratified by cardiorespiratory fitness. Methods Consecutive AF patients referred for treadmill exercise stress test (EST) and transthoracic echocardiogram (TTE) between March and December 2020 were screened for inclusion. Treadmill EST was symptom limited and age and gender predicted CRF was calculated with conventional formulas. Speckle tracking software was used to obtain LAS from apical 4 and 2 chamber views and mean measurements for LASr and LASb were calculated. Those achieving Results After exclusions, 141 patients in sinus rhythm were included in the analysis. Baseline characteristics were not significantly different between groups. Ejection fraction (63.6 ± 4.7% vs 64.8 ± 8.4%, p = 0.3) and LA volume index (33.1 ± 6.9 vs 31.4 ± 9.4 mL/m2, p = 0.3) were not different between groups. Both LASr (22.9% ± 7.4% vs 27.6% ± 11.4%, p = 0.02) and LASb (8.2% ± 4.7% vs 12.1% ± 6.8%, p = 0.004) (figure 1) were significantly higher in the fitter group. Conclusion Patients with higher CRF showed improved LA function as per strain measurement in the absence of AF. The relationship between CRF and left atrial function warrants further research. Abstract Figure. LASr and LASb by CRF

This study sought to characterize associations of total and beverage-specific alcohol consumption with incident atrial fibrillation (AF).Although binge drinking and moderate to high consumption of alcohol are both established risk factors for AF, comparatively less is known about the effect of low alcohol consumption and whether associations differ by specific alcoholic beverages.Using data from the UK Biobank, total and beverage-specific alcohol consumption was calculated as UK standard drinks (8 g alcohol) per week. Past drinkers and those with a history of AF were excluded. Incident AF events were assessed through hospitalization and death records, and dose-response associations were characterized using Cox regression models with correction for regression dilution bias.We studied 403,281 middle-aged individuals (52.4% female). Over a median follow-up time of 11.4 years (IQR: 10.7-12.3 years), a total of 21,312 incident AF events occurred. A J-shaped association of total alcohol consumption was observed, with lowest risk of AF with fewer than 7 drinks/week. Beverage-specific analyses demonstrated harmful associations of beer/cider consumption with any consumption. In contrast, consumption of red wine, white wine, and spirits up to 10, 8, and 3 drinks/week, respectively, was not associated with increased risk.In this predominantly White population, low levels of alcohol consumption (7 U.K. standard drinks [56 g alcohol]/week) were associated with lowest AF risk. Low consumption of red and white wine and very low consumption of spirits may not be associated with increased AF risk, whereas any consumption of beer/cider may be associated with harm. These findings may have important implications for the primary prevention of AF that should be explored in future studies.

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end‐tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30‐minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5‐minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age‐ and sex‐matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P ≥0.4). The CBFv decreased in both groups (condition, P =0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (−7.8% versus −1.8%; interaction, P =0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P =0.027) and a greater increase in symptom scores at study completion (interaction, P P >0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.