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Aims This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or permanent SR (defined as ≥6 months of SR until end of study) were calculated using Kaplan–Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56–0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09–1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling. Clinical trial registration NCT00174785

Catheter ablation for treatment of atrial fibrillation (AF), AF ablation, is more effective than antiarrhythmic drugs in reducing AF burden, reducing symptoms and increasing health-related quality of life. Although females more often experience AF-related symptoms, and have more severe symptoms, have lower quality of life, and experience more serious adverse effects of antiarrhythmic drugs than males, they are less likely to undergo AF ablation. Potential explanations for the disparity include older age at diagnosis, longer AF duration, a greater number of comorbidities, more extensive atrial fibrosis, and presumed lower success rate and more complications after AF ablation in women. Studies have failed to show sex-related differences in AF recurrence or serious complications following AF ablation but show more nuisance bleeds in women. Ethnic minorities, such as African Americans and Latin Americans, and individuals of low socioeconomic status are also less likely to undergo AF ablation, possibly associated with greater numbers of comorbidities, lack of patient advocacy, healthcare costs, and inadequate insurance coverage. Inclusion of marginalized patient groups in clinical trials of AF treatment and a personalized, patient-centered approach may expand equality in utilization of AF ablation.

Aims A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. Methods A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost-utility ratio. Results Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81-90%) to 866 (MPR

The improvement of Patient-reported outcomes, such as health-related quality of life, is the main indication for atrial fibrillation ablation. Despite this guideline derived indication for an AF ablation procedure the current standardized primary endpoint in AF ablation trials is still rhythm-related, and primarily a 30-second long AF episode. The review presents reflections on the non-rational arguments of using rhythm related endpoints rather than Patient-reported outcomes in AF ablation procedure trials despite the mismatch between many of the rhythm related variables and symptoms. Arguments for health-related quality of life as the most optimal primary endpoint in clinical trials are presented while atrial fibrillation burden is presented as the most optimal electrical complementary endpoint, apart from being the major variable in mechanistic trials.

Aims To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min… Methods and results In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min… Conclusion A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.

BACKGROUND: Early identification of patients at risk of congestive heart failure (HF) may alter their poor prognosis. The aim was therefore to test whether simple electrocardiographic variables, the P-wave and PR-interval, could predict incident HF. METHODS: The PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study (1016 individuals all aged 70 years, 50% women) was used to identify predictors of HF. Subjects with prevalent HF, QRS duration ≥ 130 ms, atrial tachyarrhythmias, implanted pacemaker/defibrillator, second- and third-degree atrioventricular block or delta waves at baseline were excluded. Cox proportional hazard analysis was used to relate the PR interval, P-wave duration (Pdur) and amplitude (Pamp), measured in lead V1, to incident HF. Adjustment was performed for gender, RR-interval, beta-blocking agents, systolic blood pressure, body mass index and smoking. RESULTS: Out of 836 subjects at risk, 107 subjects were diagnosed with HF during a follow-up of 15 years. In the multivariate analysis, there was a strong U-shaped correlation between Pdur in lead V1 and incident HF (P = 0.0001) which was significant for a Pdur < 60 ms [HR = 2.75; 95% CI: 1.87-4.06, at Pdur 40 ms] but not for prolonged Pdur. There was no significant relationship between incident HF and the PR-interval or the Pamp. A Pdur < 60 ms improved discrimination by 3.7% when added to the traditional risk factors including sex, RR-interval, beta-blocking agents, systolic blood pressure, BMI and smoking (P = 0.048). CONCLUSIONS: A short Pdur, an easily measured parameter on the ECG, may potentially be a useful marker of future HF, enabling its early detection and prevention, thus improving outcomes.

BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Cardiac implantable electronic devices (CIED) are potentially life-saving treatments for several cardiac conditions, but are not without risk. Despite dissemination of recommended strategies for prevention of device infections, such as administration of antibiotics before implantation, infection rates continue to rise resulting in escalating health care costs. New trials conveying important steps for better prevention of device infection and an EHRA consensus paper were recently published. This document will review the role of various preventive measures for CIED infection, emphasizing the importance of adhering to published recommendations. The document aims to provide guidance on how to prevent CIED infections in clinical practice by considering modifiable and non-modifiable risk factors that may be present pre-, peri-, and/or post-procedure.

Aim The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims. Methods and results Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P, Graphical Abstract

The infection rate associated with cardiac implantable electronic devices has increased over the past decades. A recent study found the prevalence of infection after cardiac resynchronization therapy to be more than tenfold higher than reported to the national registry. Risk factors for infection can be host-, procedure-, or device-related, the most important being recent manipulation of the device. Perioperative contamination is the most frequent source, but leads can also be secondarily infected from bacteremia, most commonly with staphylococci. Patients with pocket infection often present with erythema and swelling over the pocket, whereas systemic infection usually produces fever and, in its most severe form, endocarditis. Parenteral empiric antimicrobial therapy should be initiated after drawing blood cultures and followed by transesophageal echocardiogram. Management also includes prompt device extraction, followed by a reevaluation of the indication before reimplantation. Education of operators, related personnel, and referring physicians, prevention of modifiable risk factors, and accurate reporting to national registries are critical actions to limit complications.

Infections related to cardiac implantable electronic devices (CIED) are associated with significant morbidity and mortality. Despite optimal use of antimicrobials and other preventive strategies, the incidence of CIED infections is increasing over time leading to considerable costs to the healthcare systems. Recently, antibiotic-eluting envelopes (AEEs) have been introduced as a promising technology to prevent CIED infections. This review will address the current evidence on stratification of CIED infection risk, present the rationale behind AEE, and summarize the currently available evidence for CIED infection prevention as well as demonstrate the cost-effectiveness of this novel technology.

ObjectivesThe association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges.MethodsBaseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category.ResultsAmong 3333 patients, 728 (21.8%) were classified as normal (BMI 2), 1537 (46.1%) as overweight (BMI 25.5–29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p2led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112).ConclusionsPatients with a baseline BMI ≥30 kg/m2have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

Background: Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history. Hypothesis: Outcomes with dronedarone may also be impacted by duration of AF/AFL history. Methods: In this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history)

Background Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI). This study presents a subanalysis of real-world 1-year follow-up data from the ESC-EHRA EORP Atrial Fibrillation (AF) Ablation Long-Term registry to analyze the usage of adenosine during PVI treatment in terms of rhythm outcome and safety. Methods The registry consists of 104 participating centers in 27 countries within the European Society of Cardiology. The registry data was split into an adenosine group (AG) and no-adenosine group (NAG). Procedure characteristics and patient outcome were compared. Results Adenosine was administered in 10.8% of the 3591 PVI patients included in the registry. Spain, the Netherlands, and Italy included the majority of adenosine cases (48.8%). Adenosine was applied more often in combination with open irrigation radiofrequency (RF) energy (74.7%) and less often in combination with nonirrigated RF energy (1.6%). After 1 year, a higher percentage of the AG was free from AF compared with the NAG (68.9% vs 59.1%, p p p = 0.991). Conclusions The use of adenosine was associated with a better rhythm outcome after 1 year follow-up and seems more useful in patients treated with RF energy compared with patients treated with cryo energy. Given the improved rhythm outcome at 1-year follow-up, it seems reasonable to encourage the use of adenosine during RF AF ablation.

AimsCardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF) and electrical dyssynchrony. The European Society of Cardiology (ESC) Guidelines provide evidence-based recommendations indicating optimal patient selection for CRT implantation in both the 2013 European Heart Rhythm Association (EHRA) and the 2016 Heart Failure Association (HFA) Guidelines. We assessed the adherence to guidelines and identified factors associated with guideline adherence.Methods and resultsIn 2016, the HFA and EHRA conducted the CRT Survey II in 42 ESC countries. The data collected were sufficient to evaluate adherence to guidelines in 8021 patients. Of these, 67% had a Class I guideline indication for CRT implantation, which was significantly correlated with female gender (1.70, P ConclusionImplanters in ESC member states demonstrate a high degree of adherence to ESC guidelines with 98% of implants having a documented Class I, IIa or IIb indication. Cardiac resynchronization therapy implantation without a Class I indication was more likely in men, patients age ≥75 years, with HF of ischaemic origin and in patients admitted to hospital acutely.

Aims Rhythm control management in patients with atrial fibrillation (AF) may be unequal across Europe. The aim of this study was to investigate how selective the patient cohort referred for AF ablation is, as compared to the general AF population in Europe, and to describe the governing mechanisms for such selection. Methods and results Descriptive comparative statistical analyses of the baseline characteristics were performed between the cohorts of Atrial Fibrillation Ablation Long-Term (ESC EORP AFA-LT) registry, designed to provide a picture of contemporary real-world AF ablation, and the AF population from the AF-General (ESC EORP AF-Gen) pilot registry. Data collection was performed using a web-based system. In the AFA and in the Atrial Fibrillation General (AFG) pilot registries, 3593 and 3049 patients were enrolled, respectively. Patients who underwent AF ablation were younger, more commonly male, and had significantly less comorbidities. Atrial Fibrillation Ablation patients often presented without comorbidities, resulting in a lower risk of stroke (CHA2DS2-VASc ≥5: 2.9% vs. 24.5%, all P 1 and more prevalent AF-related symptoms such as palpitations, fatigue, and weakness (all P Conclusion The comparison of the patient cohorts in the AFA and AFG registries showed that AF ablation in European clinical practice is mostly performed in relatively young, symptomatic and relatively healthy patients.

ObjectiveThere has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics.MethodsMEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF.ResultsOne hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing.ConclusionsOur analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF.PROSPERO registration numberCRD42020219844.

The current AF definition requires recording in classical ECG or Holter ECG at least a 30-s episode of AF. According to the current definition, the presence of frequent shorter episodes of fast atrial arrhythmia or episodes of arrhythmia identified with widely used screening tools requires subsequent steps to establish a definite diagnosis of AF. The use of different clinical risk scores can help to refine target populations better. Due to the unpredictable and highly variable nature of AF episodes, a monitoring time lasting 2 weeks or longer is preferable to maximize the possibility of identifying subjects with AF. Several capabilities are currently available for AF search/screening, including devices based on plethysmographic pulse assessment, belts and vests for long-term ECG monitoring, modern Holter capabilities, and ILRs. Decision-making regarding using particular of them should depend on proof of efficacy based on published data, patient characteristics, and purpose of monitoring (screening/search). Additionally, all subjects with CIED with the possibility of atrial sensing should be carefully evaluated to identify AHREs. In large-scale screening projects, ML and AI could provide the appropriate interpretation of large databases containing the results of a giant number of participants. From the patient perspective, participation in screening has positive but also negative aspects. Therefore, each patient should be able to accept or refuse to participate in a screening programme, being fully aware of the potential benefits or hurdles of the screening. As the first step of shared decision-making, identifying a patient’s values, goals, and preferences is mandatory.

Aims To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing cardiac pacing. Methods and results Under the auspice of the Clinical Practice Guideline Quality Indicator Committee of the European Society of Cardiology (ESC), the Working Group for cardiac pacing QIs was formed. The Group comprised Task Force members of the 2021 ESC Clinical Practice Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy, members of the European Heart Rhythm Association, international cardiac device experts, and patient representatives. We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care by constructing a conceptual framework of the management of patients receiving cardiac pacing, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. Four domains of care were identified: (i) structural framework, (ii) patient assessment, (iii) pacing strategy, and (iv) clinical outcomes. In total, seven main and four secondary QIs were selected across these domains and were embedded within the 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization therapy. Conclusion By way of a standardized process, 11 QIs for cardiac pacing were developed. These indicators may be used to quantify adherence to guideline-recommended clinical practice and have the potential to improve the care and outcomes of patients receiving cardiac pacemakers.

Background Current classification systems recommended by major international guidelines are based on a single domain of atrial fibrillation (AF): temporal pattern, symptom severity or underlying comorbidity. Lack of integration between these various elements limits our approach to patients with AF and acts as a barrier against the delivery of better holistic care. The 4S-AF classification scheme was recently introduced as a means for the characterisation of patients with AF. It comprises of 4 domains: stroke risk (St), symptoms (Sy), severity of AF burden (Sb) and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and effects of individual domains on outcomes in AF. Methods Patients with AF from 250 centres across 27 participating European countries were included. All patients were over 18 years old and had electrocardiographic confirmation of AF within 12 months prior to enrolment. Data on demographics and comorbidities were collected at baseline. Individual domains of the 4S-AF scheme were assessed using the CHA2DS2-VASc score (St), European Heart Rhythm Association classification (Sy), temporal classification of AF (Sb), and cardiovascular risk factors and the degree of left atrial enlargement (Su). Each of these domains were used during multivariable cox regression analysis. Results A total of 6321 patients were included in the present analysis, corresponding to 57.0% of the original cohort of 11096 patients. The median age of patients was 70 (interquartile range [IQR] 62–77) years with 2615 (41.4%) females. Among these patients, 528 (8.4%) had low stroke risk (St=0), 3002 (47.5%) no or mild symptoms (Sy=0), 2558 (40.5%) newly diagnosed or paroxysmal AF (Sb=0), and 322 (5.1%) no cardiovascular risk factors or left atrial enlargement (Su=0). Median follow-up was 24 months. Using multivariable cox regression analysis, independent predictors of all-cause mortality were (St) (adjusted hazard ratio [aHR] 8.21 [95% CI, 2.60–25.9]), (Sb) (aHR 1.21 [95% CI, 1.08–1.35]) and (Su) (aHR 1.27 [95% CI, 1.14–1.41]). For cardiovascular mortality and any thromboembolic event, only (Su) (aHR 1.73 [95% CI, 1.45–2.06]) and (Sy) (aHR 1.29 [95% CI, 1.00–1.66]) were statistically important, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Conclusion Overall, we demonstrated that the 4S-AF scheme may be used to provide clinical characterisation of patients with AF using routinely collected data, and each of the domains within the 4S-AF scheme were independently associated with adverse long-term outcomes of all-cause mortality, cardiovascular mortality and/or any thromboembolic event. Funding Acknowledgement Type of funding sources: None.

Background The 2020 European Society of Cardiology (ESC) guidelines provide detailed recommendations for the management of patients with atrial fibrillation (AF). In symptomatic patients, AADs are advised for rhythm control. Purpose This study was designed to investigate AAD treatment practices and adherence to guidelines in four European countries. Methods An online survey (n=321) of cardiologists or cardiac electrophysiologists (CDs) and interventional electrophysiologists (EPs) was conducted in Germany (DE; n=83), Italy (IT; n=95), Sweden (SE; n=60) and the UK (n=83). Respondents were actively treating ≥10 patients with AF. Results (1) The majority of physicians considered guidelines to be the most important non-patient factor influencing their AF management practices (pooled: 65%; range: 55–72%), with 96% (range: 89–100%) following ESC guidelines. Although amiodarone use was most frequent in heart failure with reduced left ventricular (LV) ejection fraction (pooled: 91%; range: 88–93%) where it is a recommended first-line option, non-adherent AAD selection was common. Amiodarone was frequently selected as a typical treatment choice for minimal/no structural heart disease (SHD) where it is not recommended for initial therapy; this was particularly common in the UK versus SE (Figure 1). Other deviations included use of class 1C drugs in those with coronary artery disease (CAD) (with the exception of SE; Figure 1) and other SHD, as well as use of sotalol in LV hypertrophy (pooled: 30%) and renal impairment (Figure 1). Furthermore, absence of inpatient initiation of sotalol was generally high, with the exception of SE (Figure 1). (2) Sotalol and dronedarone use in CAD varied between country (pooled: 28% [range: 16–41%] and pooled: 19% [range: 10–54%], respectively). (3) CDs and EPs used rhythm control as initial therapy in most patients with paroxysmal AF (PAF); however, other than SE, this was not the case for persistent AF (Figure 2). (4) AADs were preferred over ablation as initial therapy for individuals with infrequent, mildly symptomatic PAF (pooled: 61%), with the exception of SE (48%). Ablation was favoured for most patients with frequent, symptomatic PAF; however, in SE, AADs were preferred for infrequent, highly symptomatic PAF (53%) and frequent, symptomatic PAF (53%). (5) Rhythm control therapies were selected for asymptomatic or subclinical AF; AADs were used more often (average: 41% [range: 22–60%]; ablation was used less frequently (average: 11% [range: 2–18%]). Conclusion Despite assertion that guidelines are the primary determinant for rhythm control treatment decisions, non-adherence was notable in European practice. While deviation may be reasonable in select individual patients, in general, non-adherence could compromise patient safety. As such, establishing the drivers of non-adherent practices is key, and education directed at clinicians to improve optimal and safe use of AADs is warranted in Europe. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

Background There is a long-standing and unresolved controversy over the effects of digoxin on mortality. Furthermore, there is scarce evidence comparing the use of digoxin to beta-blocker in the general population with atrial fibrillation (AF). In this study, we aimed to evaluate the effects of digoxin over beta-blocker therapy among patients with AF. Methods Patients from the EORP-AF General Long-Term Registry with AF who were treated with either digoxin or beta-blocker were included. All patients were over 18 years old and had documented evidence of AF within 12 months prior to enrolment. The outcomes of interest were all-cause mortality, cardiovascular (CV) mortality, non-CV mortality and number of patients with unplanned hospitalisation (total and AF-related). These were recorded until the last known follow-up available. Results Of 6377 patients, 549 (8.6%) and 5828 (91.4%) were treated with digoxin and beta-blockers, respectively. Patients in the digoxin group were older (73 vs. 71 years, p Over 24 months follow-up, there were 550 (8.6%) all-cause mortality and 1304 (23.6%) patients with unplanned emergency hospitalisation. Digoxin use was associated with increased all-cause mortality (hazard ratio [HR] 1.90 [95% CI, 1.48–2.44]), both from CV and non-CV causes (CV: HR 2.21 [95% CI, 1.49–3.26]); non-CV: HR 1.70 [95% CI, 1.04–2.79]). There was no statistical difference in terms of unplanned emergency hospitalisation (HR 0.99 [95% CI, 0.80–1.21]) and AF-related hospitalisation (HR 0.78 [95% CI, 0.58–1.06]) between both groups. Using multivariable cox regression analysis, digoxin compared to beta-blocker therapy was independently linked to increased all-cause mortality (HR 1.52 [95% CI, 1.11–2.09]) and CV mortality (HR 1.82 [95% CI, 1.11–2.97]), but was not related to non-CV mortality (HR 1.31 [95% CI, 0.71–2.41]), emergency hospitalisation (HR 0.91 [95% CI, 0.71–1.16]) or AF-related hospitalisation (HR 0.88 [95% CI, 0.62–1.24]), after adjustment for known risk factors. Conclusion We demonstrated that the use of digoxin was independently associated with excess all-cause mortality, driven by CV death, but was non-inferior to beta-blocker in terms of preventing unplanned emergency or AF-related hospitalisation, after accounting for important risk factors. Funding Acknowledgement Type of funding sources: None.

Objectives This study sought to compare sex difference for procedural aspects and complications in the European Society of Cardiology CRT Survey II, exploring whether adverse events were related to the type of CRT device implanted. Background Sex-related differences in procedural aspects and complications in patients undergoing cardiac resynchronization therapy (CRT) implantation has not been explored in a real-life population. Methods A post-hoc analysis of procedural data and complications in different sexes and factors associated with events was performed from data collected in the European Society of Cardiology CRT Survey II. Results Of all patients (n = 11,088) included, 24.3% were women. The mean age (70 years of age) of male and female recipients was similar. Female patients more frequently had an idiopathic cardiomyopathy (67.4% vs. 44.1%) and fewer comorbidities, including atrial fibrillation (34.8% vs. 42.8%), diabetes (29.1% vs. 32.1%), chronic obstructive lung disease (10.3% vs. 12.6%), and renal failure (28.7% vs. 31.9%), compared with men. More women compared with men had a pacemaker (56.6% vs. 46.3%) and much less often an implantable cardioverter-defibrillator (CRT-D) (19.0% vs. 34.7%) implant. Periprocedural event rate was the highest in women with CRT with defibrillator (7.1% vs. 4.8% in men), followed by women with a CRT with pacing (5.5% vs. 4.4% in men). The higher periprocedural event rate in CRT-D women was attributable primarily to the occurrence of pneumothorax (1.4%), coronary sinus dissection (2.1%), and pericardial tamponade (0.3%). The rate of in-hospital major adverse events (6.0%) and complications necessitating reoperation (4.0%) was not different among sex and device type. Conclusions Women are more likely to experience adverse procedure-related events during CRT implantation. Thus, preventive strategies should be employed to minimize complication rate.

Aims Monitoring of patients after ablation had wide variations in the ESC-EHRA atrial fibrillation ablation long-term (AFA-LT) registry. We aimed to compare four different monitoring strategies after catheter AF ablation. Methods and results The ESC-EHRA AFA-LT registry included 3593 patients who underwent ablation. Arrhythmia monitoring during follow-up was performed by 12-lead electrocardiogram (ECG), Holter ECG, trans-telephonic ECG monitoring (TTMON), or an implanted cardiac monitoring (ICM) system. Patients were selected to a given monitoring group according to the most extensive ECG tool used in each of them. Comparison of the probability of freedom from recurrences was performed by censored log-rank test and presented by Kaplan–Meier curves. The rhythm monitoring methods were used among 2658 patients: ECG (N = 578), Holter ECG (N = 1874), TTMON (N = 101), and ICM (N = 105). A total of 767 of 2658 patients (28.9%) had AF recurrences during follow-up. Censored log-rank test discovered a lower probability of freedom from relapses, which was detected with ICM compared to TTMON, ECG, and Holter ECG (P Conclusion Comparing all main electrocardiographic monitoring methods in a large patient sample, our results suggest that post-ablation recurrences of AF are significantly underreported by TTMON, ECG, and Holter ECG. The ICM estimates AF ablation recurrences most reliably and should be a preferred mode of monitoring for trials evaluating novel AF ablation techniques.

Clinical characteristics of heart failure patients undergoing atrial fibrillation ablation today in Europe. Data from the atrial fibrillation registries of the European Society of Cardiology and the European Heart Rhythm Association.

BACKGROUND: The diagnosis of ARVC remains complex requiring both imaging and electrocardiographic (ECG) techniques. The purpose was therefore to investigate whether QRS dispersion assessed by body surface mapping (BSM) could be used to detect early signs of ARVC, particularly in gene carriers. METHODS: ARVC patients, gene carriers without a history of arrhythmias or structural cardiac changes and healthy controls underwent 12-lead resting ECG, signal-averaged ECG, echocardiographic examination, 24-hours Holter monitoring, and BSM with electrocardiographic imaging. All 252-leads BSM recordings and 12-leads ECG recordings were manually analyzed for QRS durations and QRS dispersion. RESULTS: Eight controls, 12 ARVC patients with definite ARVC and 20 healthy gene carriers were included. The ECG-QRS dispersion was significantly greater in ARVC patients (42 vs. 25 ms, p 40 ms) in 4/20 healthy gene carriers without signs of ARVC, which may indicate early depolarization changes. CONCLUSIONS: QRS dispersion, when assessed by BSM versus 12-lead ECG, seem to better distinguish ARVC patients from controls, and could potentially be used to detect early ARVC in gene carriers. Further studies are required to confirm the value of BSM-QRS dispersion in this respect.

Purpose Atrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF. Methods Patients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1–3 h after, and at 7–10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels. Results Forty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0–1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7–10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without. Conclusion Although LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7–10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Sanofi Introduction In the recent 2020 European Society of Cardiology (ESC) guidelines, sotalol was downgraded from a Class IA to a llbA recommendation and advised not to be prescribed in patients with specific co-morbidities. All patients given sotalol should also be closely monitored for proarrhythmic risk factors. To date, American guidelines have not changed. Our study sought to understand the use of sotalol in AF patients and monitoring compliance across the USA and in the EU, with regards to the recent ESC guideline change. Method An online physician survey of cardiologists, cardiac electrophysiologists (EPs) and interventional EPs (N = 569) was conducted in the USA, Germany, Italy and the UK. All respondents were actively treating ≥10 AF patients who received drug therapy and/or who had received or were referred for ablation. This survey included topics on AF types and antiarrhythmic drug (AAD) treatment practices in those with AF +/- co-morbidities (including left ventricular hypertrophy [LVH], LV heart failure, and sinus node dysfunction or renal impairment). Results Sotalol was prescribed across all patient sub-groups, with high use in those with hypertension (49% of physicians) and revascularised coronary artery disease (44%). Sotalol use was consistently higher among US respondents than EU clinicians across co-morbidity categories (heart failure with reduced ejection fraction: 25% vs 14% [guideline deviation]; hypertension: 53% vs 44%; valve disease: 33% vs 23%; recent myocardial infarction [MI]: 44% vs 22%; old MI: 52% vs 31%, respectively). Use was also generally higher among EPs compared with cardiologists, but remained low in patients with minimal or no structural heart disease across all groups. Many respondents prescribed sotalol in those with LVH (35%) or renal impairment (22%), despite guidelines advising against this due to proarrhythmia risk. This contrasts with expressed respondent concerns, as 43% cited ventricular proarrythmia risk as a reason for not using sotalol. Although respondents noted concern over such risks, as per the new guidelines, routine monitoring for these factors was not performed as follows: electrocardiograms (ECG) (19% [US: 23%; EU: 15%]), renal function assessment (42% [US: 36%; EU: 50%]) or electrolyte monitoring (48% [US: 49%; EU: 46%]). Respondents reported sotalol is typically initiated in hospital (45% of patients) or in outpatients with intensive ECG monitoring (37%), but is also being started in non-monitored outpatients (19%). Conclusions Although sotalol use among EU clinicians was lower compared with the USA, which may reflect recent ESC guideline changes, the extent of monitoring practices that would indicate avoidance in those with proarrhythmic risk factors was insufficient. The lack of routine monitoring for specific factors, such as renal impairment or electrolytes, and unmonitored outpatient initiation highlights an ongoing need for further education on maximising safety when using AADs. Abstract Figure.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Sanofi Introduction The 2020 European Society of Cardiology and the 2019 USA (AHA/ACC/HRS) guidelines recommend the use of AADs for rhythm control in patients with symptomatic AF. This study sought to understand AAD treatment practices and adherence to guidelines across the EU and the USA. Method An online physician survey of cardiologists, cardiac electrophysiologists and interventional electrophysiologists (N = 569) was conducted in the USA, Germany, Italy and the UK. All respondents were actively treating ≥10 AF patients who received drug therapy and/or who had received or were referred for ablation. This extensively detailed survey explored questions on physician demographics, AF types, and drug treatment and ablation practices. Results: Of the responses obtained (1) Amiodarone was used frequently across co-morbidity categories (highest use in those with heart failure with reduced left ventricular ejection fraction [LVEF] [80%]), including in those in which it is not indicated for initial therapy (minimal or no structural heart disease: 26%). Other deviations from guideline recommendations, include: class 1C drugs were used with structural heart disease, including coronary artery disease (CAD) (average class 1C use in CAD-related comorbidities: 6%); sotalol was used with renal dysfunction (22%); and drugs such as sotalol and dofetilide were initiated out of hospital (56% and 17% of respondents, respectively). (2) Nonetheless, a majority of respondents (53%) considered guidelines as the most important non-patient factor in influencing their choice of AF management. (3) Rhythm control was selected more frequently as primary therapy for paroxysmal AF (PAF) (59% of patients) while rate control was used more often for persistent AF (53%). (4) For PAF, AADs were preferred as 1st line more often than ablation, especially if PAF was infrequent and mildly symptomatic (59% of respondents) while ablation was preferred more if frequent symptomatic PAF and for recurrent persistent AF. (5) Rhythm control (AAD or ablation) was chosen in notable numbers for asymptomatic AF and subclinical AF (AADs: 36% and 37%, respectively; ablation: 9% and 14%, respectively). (6) AAD use for those with a first or recurrent episodes of symptomatic AF was 60% or 47%, respectively. (7) Efficacy and safety were chosen as the most important considerations for choice of specific rhythm control therapy (49% and 33%, respectively), and reduction of mortality and cardiovascular hospitalisation (23%) were as important as maintaining sinus rhythm (26%) for rhythm therapy goals. Conclusions Although surveyed clinicians consider guidelines important, deviations in patient types and treatments chosen that compromise safety or were not indicated were common. Findings suggest a lack of understanding of the pharmacology and safe use of AADs, highlighting an important need for further education. Abstract Figure.

Atrial fibrillation (AF) is a complex condition requiring holistic management with multiple treatment decisions about optimal thromboprophylaxis, symptom control (and prevention of AF progression), and identification and management of concomitant cardiovascular risk factors and comorbidity. Sometimes the information needed for treatment decisions is incomplete, as available classifications of AF mostly address a single domain of AF (or patient)-related characteristics. The most widely used classification of AF based on AF episode duration and temporal patterns (that is, the classification to first-diagnosed, paroxysmal, persistent/long-standing persistent, and permanent AF) has contributed to a better understanding of AF prevention and treatment but its limitations and the need for a multidimensional AF classification have been recognized as more complex treatment options became available. We propose a paradigm shift from classification toward a structured characterization of AF, addressing specific domains having treatment and prognostic implications to become a standard in clinical practice, thus aiming to streamline the assessment of AF patients at all health care levels facilitating communication among physicians, treatment decision-making, and optimal risk evaluation and management of AF patients. Specifically, we propose the 4S-AF structured pathophysiology-based characterization (rather than classification) scheme that includes four AF- and patient-related domains—Stroke risk, Symptoms, Severity of AF burden, and Substrate severity—and provide a hypothetical model for the use of 4S-AF characterization scheme to aid treatment decision making concerning the management of patients with AF in clinical practice.

Highlights • Assessing the relationship between atrial fibrillation and quality of life. • Implantable loop recorders assessed rhythm continuously in symptomatic patients. • Atrial fibrillation burden, episode duration and frequency were included. • Higher atrial fibrillation burden was associated with impaired quality of life., Aims To assess the relation between atrial fibrillation (AF) characteristics and health-related quality of life (QoL), and which AF characteristic had the greatest impact. Method The AF characteristics burden (percentage of time in AF), duration and number of AF episodes/month were obtained from implantable cardiac monitors during the 2-month run-in period in 150 patients included in the randomized CAPTAF trial comparing early ablation and antiarrhythmic drug therapy. The QoL was measured by the General Health and Vitality dimensions of the 36-Item Short-Form Health Survey. AF characteristics were analysed continuously and in quartiles (Q1-Q4). Results Greater AF burden (p = 0.003) and longer AF episodes (p = 0.013) were associated with impaired QoL (Vitality score only) in simple linear regression analyses. Greater AF burden was, however, the only AF characteristic associated with lower QoL, when adjusted for sex, type of AF, hypertension, heart rate above 110 beats per minute during AF, and beta-blocker use in multiple linear regression analyses. For every 10% increase in AF burden there was a 1.34-point decrease of Vitality score (95% confidence interval (CI) −2.67 to −0.02, p = 0.047). The Vitality score was 12 points lower (95% CI −22.73 to −1.27, p = 0.03) in patients with an AF burden > 33% (Q4) versus those with

Background The implantation rates of cardiac implantable electronic devices have steadily increased, accompanied by a steeper rise of device related infections (DRI). Hypothesis The prevalence of DRI for cardiac resynchronization therapy (CRT) is higher in clinical practice than reported previously, even at a university hospital, and likely higher than reported to the national device registry. Methods Electronic medical records of consecutive patients undergoing a CRT procedure between January 2016 and December 2017 were analyzed. Clinical history, procedure related variables and complications were reviewed by specialists in cardiology and infectious diseases. Results A total of 171 patients, mean aged 74 years, 138 males (80.7%) were included. Twelve DRI occurred in 10 patients during mean 2.5 years follow‐up, giving a prevalence of 7% (incidence of 29/1000 person‐years). Reoperation, pocket haematoma, ≥3 procedures, previous device infection and indwelling central venous line were the strongest predictive factors according to univariate analysis. Out of 63/171 (36.8%) major complications, 31(49.2%) were lead‐related. There were 49/171 (28.7%) reoperations and 15/171 (8.8%) minor complications. The number major complications and DRI reported to the national device registry were 7/171 (4.1%) and 2/171 (0.6%), respectively, reflecting a 5‐fold underreporting. Conclusions The high rate of CRT device infections is in sharp contrast to those reported by others and to the national device registry. Although a center specific explanation cannot be excluded, the high rates highlight a major issue with registries, reinforcing the need for better surveillance and automatic reporting of device related complications.

Aims Transvenous lead extraction is associated with a significant risk of complications and identifying patients at highest risk pre-procedurally will enable interventions to be planned accordingly. We developed the ELECTRa Registry Outcome Score (EROS) and applied it to the ELECTRa registry to determine if it could appropriately risk-stratify patients. Methods and results EROS was devised to risk-stratify patients into low risk (EROS 1), intermediate risk (EROS 2), and high risk (EROS 3). This was applied to the ESC EORP European Lead Extraction ConTRolled ELECTRa registry; 57.5% EROS 1, 31.8% EROS 2, and 10.7% EROS 3. Patients with EROS 3 or 2 were significantly more likely to require powered sheaths and a femoral approach to complete procedures. Patients with EROS 3 were more likely to suffer procedure-related major complications including deaths (5.1 vs. 1.3%; P Conclusion EROS successfully identified patients who were at increased risk of significant procedural complications that require urgent surgical intervention.

Background Catheter ablation has emerged as an effective therapy in patients with atrial fibrillation (AF). Despite high success rates of the method, there is still heterogeneity of outcomes and complications across Europe. A center's volume of AF ablations performed per year might also play an important role in the success rate of the procedure as compared to other confounding factors which may be different among centers (such as type of AF ablated, patient selection criteria, referral bias and/or ablation strategy). Purpose Aim of the study was to investigate differences in clinical outcomes and complication rates among European AF ablation centers related to the volume of ablations performed annually. Methods Data for this analysis were extracted from the European AF Ablation Long-Term Study, a prospective registry designed to describe the clinical epidemiology of patients undergoing AF ablation. Based on 33th and 67th percentiles of number of AF ablations performed, the participating centers were classified into high volume (HV) (≥180 procedures/year), medium volume (MV) ( Results A total of 91 centers in 26 European countries enrolled 3368 patients. There was a significantly higher reporting of cardiovascular complications in LV centers (5.2%), especially pericarditis and cardiac perforation, while the HV and MV centers reported cardiovascular complications in 3.0 and 4.3% of cases, respectively (p=0.039). Additionally, stroke incidence after ablation was significantly higher in LV centers (0.5% of cases vs 0% in HV and MV centers, p=0.008). One-year success after AF ablation ranged from 77.8% in HV vs 70.5% in LV vs 77.3% in MV centers (p Conclusions Low volume centers present slightly higher cardiovascular complications' and stroke incidence and a lower unadjusted success rate after AF ablation. On the other hand, adjusted overall complication and recurrence rates are non-significantly different among different volume centers, a fact reflecting inhomogeneity of patient and procedural profiles and a counterbalance between expertise and risk level among participating centers. Funding Acknowledgement Type of funding source: None

Aims The aim of the study was to investigate differences in clinical outcomes and complication rates among European atrial fibrillation (AF) ablation centres related to the volume of AF ablations performed. Methods and results Data for this analysis were extracted from the ESC EHRA EORP European AF Ablation Long-Term Study Registry. Based on 33rd and 67th percentiles of number of AF ablations performed, the participating centres were classified into high volume (HV) (≥ 180 procedures/year), medium volume (MV) ( Conclusion Low-volume centres tended to present slightly higher cardiovascular complications’ and stroke incidence and a lower unadjusted success rate after AF ablation, despite the fact that ablation procedures and patients were of lower risk compared with MV and HV centres. On the other hand, adjusted overall complication and recurrence rates were non-significantly different among different volume centres, a fact reflecting the heterogeneity of patient and procedural profiles, and a counterbalance between expertise and risk level among participating centres.

Aims Transvenous lead extraction (TLE) should ideally be undertaken by experienced operators in a setting that allows urgent surgical intervention. In this analysis of the ELECTRa registry, we sought to determine whether there was a significant difference in procedure complications and mortality depending on centre volume and extraction location. Methods and results Analysis of the ESC EORP European Lead Extraction ConTRolled ELECTRa registry was conducted. Low-volume (LoV) centres were defined as Conclusion Primary operator cardiologists in LoV centres are more likely to have extractions complicated by procedure-related deaths. There was no significant difference in procedure complications between different extraction settings. These findings support the need for TLE to be performed in experienced centres with appropriate personnel present.

AimThe purpose of this study was to compare sex differences of atrial fibrillation (AF) catheter ablation (CA) and to analyse the opportunities for improved outcomes.Methods and resultsAll data were collected from the Atrial Fibrillation Ablation Long-Term registry, a prospective, multinational study conducted by the ESC-EORP European Heart Rhythm Association (EHRA) under the EURObservational Research Programme (ESC-EORP). A total of 104 centres in 27 European countries participated. Of 3593 included patients, 1146 (31.9%) were female. Female patients were older (61.0 vs. 56.4 years; P ConclusionFemales underwent CA procedures for AF less frequently than males throughout Europe, despite more recurrent symptoms. With the same success rate, severe acute complications remained considerable in females, especially in less experienced centres.

AIM: To report the Italian data deriving from the European Society of Cardiology-EURObservational Research Program atrial fibrillation ablation long-term registry. METHODS AND RESULTS: Ten Italian centers enrolled up to 50 consecutive patients undergoing atrial fibrillation ablation. Of the 318 patients included, 5 (1.6%) did not undergo catheter ablation, 1 had ablation partially done and 62 were lost at 1-year follow-up. Women were less represented (23.6%) and the median age was 60.0 years. A total of 195 patients (62.3%) suffered paroxysmal atrial fibrillation, whereas only 9 (2.9%) had long-standing persistent atrial fibrillation. Most Italian patients (92.3%) were symptomatic but suffering fewer symptomatic events than patients enrolled in other countries (median of two events in the month preceding the ablation vs. three, respectively; P

Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight