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IntroductionAtrial fibrillation (AF) is the most common arrhythmia and imposes a high burden on the healthcare system. A nurse-led AF outpatient clinic may alleviate the burden on the cardiology outpatient clinic by triaging patients who need care by a cardiologist or general practitioner (GP). However, care and referral patterns after initial assessment in a nurse-led AF outpatient clinic are unknown. We examined the proportion of AF patients assessed in a nurse-led clinic without outpatient follow-up by a cardiologist.MethodsAll patients with AF referred to our tertiary medical centre underwent cardiac work-up in the nurse-led AF outpatient clinic and were prospectively followed. Data on patient characteristics, rhythm monitoring and echocardiography were collected and described. Odds ratio (OR) for continuing care in the nurse-led AF outpatient clinic was calculated.ResultsFrom 2014 to 2018, 478 consecutive individual patients were referred to the nurse-led AF outpatient clinic. After the initial cardiac work-up, 139 patients (29.1%) remained under nurse-led care and 121 (25.3%) were referred to a cardiologist and 218 (45.6%) to a GP. Patients who remained under nurse-led care were significantly younger, were more symptomatic, more often had paroxysmal AF and had less comorbidities than the other two groups. After multivariable testing, CHA2DS2-VASc score ≥ 2 was associated with discontinued nurse-led care (OR 0.57, 95% confidence interval 0.34–0.95).ConclusionAfter initial cardiac assessment in the nurse-led outpatient clinic, about half of the newly referred AF patients were referred back to their GP. This strategy may reduce the burden of AF patients on secondary or tertiary cardiology outpatient clinics.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Happitech. Provided the mobile photoplethysmography application Background Undiagnosed atrial fibrillation (AF) poses a great risk for stroke in high-risk patients. Different screening strategies have been developed to identify these patients. Geriatric patients often have multimorbidity, and are to be considered a population at very high risk for development of AF and cardiovascular events, but may have less access to wearable screening devices. Purpose The Dutch multicentre study into opportunistically screening of Geriatric patients for Atrial Fibrillation using a PPG smartphone App (the Dutch-GERAF Study) applies opportunistic screening to ambulatory geriatric patients, to identify new cases of AF and optimize stroke prevention. This preliminary analysis describes the feasibility and willingness to use of a smart phone photoplethysmography (PPG) application in an ambulatory cohort. Method Analysis of participation data and PPG use, of all included patients aged 70 years or older within the GERAF study. The GERAF study is a multicentre study on opportunistic screening for AF using a PPG application among patients visiting a geriatric outpatient clinic. All patients without a pacemaker/ICD, severe tremor, or severe dementia were invited to participate, during a 6 months screening period. Patients were stimulated to use the application at home on their own mobile device at least 3 times within 6 months following inclusion. If preferred by the patient, the application was installed on the mobile device of a spouse or other family member. The PPG signals were analysed using the commercially available algorithm. Results Data on PPG use for patients was available for 568 patients. Of these, 122 (21.5%) had a history of AF, and therefore not included in this analysis. Data on PPG use was analysed of 446 patients, 240 were female (54%), average age was 79 ± 5.5 years, the oldest patient was 95 years old. In total, patients performed 2232 PPG recordings within 6 months, in which a sufficient signal was acquired in 1874 (84%) recordings. The signal appeared sufficient at the first attempt in 79.3% of the recordings. In case of a failed first attempt, 60.5% of the patients immediately performed at least one extra recording until sufficient signal quality was achieved, and overall 61.2% of the patients performed at least 2 PPG recordings. Only 69 (15.5%) patients who consented to participation, did not perform any recordings. Conclusion This analysis of preliminary GERAF PPG data shows that very old subjects (with a mean age of almost 80 years) are willing and able to use eHealth applications on a mobile device. Most PPG recordings were of sufficient signal quality, and more than half of the patients were willing to perform repeated recordings.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by Netherlands Organization for Health Research and Development Background Myeloperoxidase (MPO), an enzyme most abundantly expressed by neutrophils, is increased in the atrial tissue of AF patients and is associated with treatment failure. Moreover, MPO increases fibrosis and AF susceptibility in mouse atria. However, how MPO promotes AF has yet to be fully established. Purpose To investigate the role of MPO in electrophysiological and structural remodelling. Methods We incubated cultured neonatal rat ventricular myocyte (NRVM) monolayers with 1 μg/mL MPO or vehicle for 24 hours. We then performed electrophysiological mapping using an 8x8 multielectrode array (MEA) setup with 100 μm-sized electrodes and 700 μm inter-electrode distance (n=8 MPO, n=7 control) and recorded action potentials (AP) using a microelectrode during pacing. Additionally, we quantified the number of fibroblasts using vimentin staining (n=5/group) and the expression of extracellular matrix (ECM) genes (COL1A1, COL8A2, FN1, CTGF, TNC, THBS2, MMP2, MMP12) using qPCR (n=4/group). Multielectrode data were analyzed with custom-made software in MATLAB. Statistical analysis was performed in R. Data presented as median [interquartile range]. Results NRVM monolayers incubated with MPO were unresponsive to pacing (5/8 vs 0/7 control) or had a higher pacing threshold (1300 [1000-2500] vs 500 [400-600] μA) (p=0.02). The percent of excitable tissue was lower in the MPO than in the control group, and the propagation of spontaneous activations was slower and more heterogeneous (index: 5 [3.6-9.5] vs 2 [1.5-3], p=0.004). More fractionated electrograms were present in MPO than in the control (29 [25-40] vs 11 [4-23] electrodes per grid, p=0.02). Re-entry was observed in 3/8 MPO-incubated monolayers vs 0/7 controls. Intracellular recordings revealed a less negative resting membrane potential (-50 [-24- -52] vs -69 [-56- -79] mV, p=0.04) and lower AP upstroke velocity (4 [2.5-14] vs 26 [22-28] V/s, p=0.01) in MPO-incubated cardiomyocytes than in the control. Moreover, relative to the control, MPO significantly increased the number of fibroblasts (126 [120-128] vs 87 [70-106] cells/0.26 mm^2, p=0.02) and the expression of MMP12 (1.17 (fold-change), p=0.04), whereas a trend toward increase was observed for other ECM genes, such as COL8A2 (1.5 (fold change), p=0.1). Conclusion Incubation of NVRM with MPO results in depolarization of cardiomyocytes and an increase in the number of fibroblasts and ECM gene expression. Thereby, MPO increases conduction heterogeneity and susceptibility to re-entry.

Background/Introduction Many clinicians estimate the frailty of patients solely using their clinical expertise instead of validated scores. Previous reports show that women are more often perceived as frail than men. It is uncertain whether the same trend is observed in patients with atrial fibrillation (AF) and if the association between perceived frailty and adverse clinical outcomes is affected by sex. Purpose To assess whether sex affects the association between frailty status and adverse clinical outcomes in patients with AF. Methods ETNA-AF-Europe is an ongoing, post-authorisation, prospective cohort study conducted in 825 centres enrolling patients with AF treated with edoxaban in 10 European countries. In this substudy on the first 2-years of follow-up, patients were categorised in four subgroups based on sex and clinician-perceived frailty at baseline. We calculated incidence rates (per 100 patient-years) of the composite endpoint of any stroke or systemic embolic event (SEE), of major bleeding, and of all-cause death for the four subgroups; and determined the unadjusted association between perceived frailty (frail vs non-frail) and each outcome, stratified by sex, using Cox proportional hazards models. To assess for consistency in our findings, we tested the same associations by sex category but using objective risk factors: age (>74 vs Results Information about frailty-status was recorded for 12,254 (93.3%) patients, of whom 8.5% of men and 15.4% of women were perceived as frail by their clinician (p Conclusion In our cohort, differences in the risks of clinical outcomes between those who were perceived as frail and those who were not is more pronounced for men than women. Because we did not observe similar trends in the associations between age or CHA2DS2-VASc score subgroups and clinical outcomes, our results indicate that clinicians perceive the extent of frailty differently in men than in women. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

ObjectivesTo determine the association between left atrial epicardial conduction time (LAECT), fibrosis and atrial fibrillation (AF) recurrence after thoracoscopic surgical ablation of persistent AF.SettingSingle tertiary care centre in the Netherlands.ParticipantsPatients with persistent AF from the randomised Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT)-trial were included. Patients eligible for thoracoscopic AF ablation were included, full inclusion and exclusion criteria were previously published. All patients underwent thoracoscopic ablation, encompassing pulmonary vein isolation with an additional roof and trigone lesion. In patients with conduction block across the roof and trigone lesion, LAECT was measured. LAECT was defined as the time to local activation at one side of the roofline on pacing from the opposite side. Collagen fibre density was quantified from left atrial appendage histology.Outcome measuresPrimary outcome: AF recurrence during 2 years of follow-up.Results121 patients were included, of whom 35(29%) were women, age was 60.4±7.8 and 51% (62) had at least one AF recurrence during 2 years of follow-up. LAECT was longer in patients with versus without AF recurrence (182±43 ms vs 147±29 ms, pConclusionLAECT is correlated with collagen fibre density and BMI and is independently associated with AF recurrence in patients with persistent AF. In these patients, LAECT appears to reflect substrate characteristics beyond clinical AF type and left atrial volume.Trial registration numberNCT01091389.

Atrial fibrillation (AF) is part of a vicious cycle that includes multiple cardiovascular risk factors and comorbidity which can promote atrial remodelling and AF progression. Most AF-related risk factors—hypertension, diabetes, sleep apnoea, obesity and sedentary lifestyle—are in essence modifiable which may prevent AF development. Treatment of associated cardiovascular conditions may prevent both symptoms and future cardiovascular events. For advanced forms of symptomatic AF refractory to lifestyle management and optimal medication, invasive ablation therapies have become a cornerstone. Although electrical trigger isolation from the pulmonary veins is reasonably effective and safe, more potent energy sources including high output-short duration radiofrequency, ultra-low cryo-energy, and electroporation, as well as more sophisticated arrays, balloons, and lattice-tipped catheter tools, are on their way to eliminate existing pitfalls and simplify the procedure. Electroanatomical navigation and mapping systems are becoming available to provide real-time information on ablation lesion quality and the critical pathways of AF in the individual patient to guide more extensive ablation strategies that may enhance long-term outcome for freedom of advanced AF. Surgical techniques, either stand-alone or concomitant to structural cardiac repair, hybrid, or convergent, with novel less invasive access options are developing and can be helpful in situations unsuitable for catheter ablation.

Background Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. Methods We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1‑year follow-up data were gathered. Results At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). Conclusions Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Aim Stroke prevention and rate or rhythm control are crucial parts of the treatment of atrial fibrillation (AF). There is limited evidence for the efficacy or safety of rate and rhythm control in elderly or very elderly patients, although this population is rapidly increasing. Therefore, we analyzed electronic health record data from outpatient cardiology clinics to give insight in prescribing patterns and mortality of both treatment strategies in the elderly patients. Methods and results We extracted data from all patients with AF who were aged >75 years, used a pharmacological rate or rhythm control strategy and visited one of the independent outpatient cardiology clinics in the Netherlands between 2007 and February 2018. This resulted in 1,497 selected patients (54% women), of whom 316 (21%) were prescribed rhythm control (consisting of class 1 or 3 antiarrhythmic drugs) and 1,181 (79%) rate control (beta blockers, calcium antagonists or digoxin). Patients aged >85 years (OR: 2.28) and those with permanent AF (OR: 2.71) were more likely to receive rate control (OR: 2.28, OR: 2.71 respectively), whereas those with paroxysmal AF were more likely to receive rhythm control (OR: 0.42). After correcting for relevant confounders, the mortality risk for patients using rhythm control was similar to patients using rate control (HR: 0.89; 95% CI: 0.70; p=0.31). Conclusion Considering the similar mortality risks in both groups, a more liberal approach in prescribing a rhythm control strategy to the healthier elderly patient with AF seems safe. Our data underscores the need for a non-inferiority trial to provide definite answers on safety of rhythm control in elderly patients with AF. Funding Acknowledgement Type of funding sources: None.

Background Non-vitamin K antagonist oral anticoagulants (NOACs) are a preferred treatment option over warfarin for anticoagulation in patients with atrial fibrillation (AF). Management decisions for thromboprophylaxis in AF need to balance the risk of stroke against the risk of bleeding. Various patient characteristics have been identified as independent risk factors for bleeding. A substantial number of bleeding events might be prevented if independent predictors of bleeding were identified. Purpose The present analysis aims at assessing age-adjusted risk predictors of major bleeding during two-year follow-up of unselected European patients with AF in the ETNA-AF-Europe registry. Methods ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational study conducted in 825 centres enrolling patients treated with edoxaban once daily in 10 European countries. Wald Chi square tested the association between risk predictors and major bleeding after adjusting for age, given that age is a well-known, strong predictor of anticoagulation-related bleeding in patients with AF. Results Overall, 13,417 patients with AF (edoxaban 60 mg: n=10,248; edoxaban 30 mg: n=3169) completed the two-year follow-up. The mean age was 73.6±9.5 years, with ∼84% of the patients aged over 65 years. Mean CHA2DS2-VASc and HAS-BLED scores were 3.2 and 2.5, respectively. 438 (3.3%) patients had a history of bleeding events at baseline, of which 138 (1.0%) had a history of major bleeding event. Univariate analysis demonstrated that recalculated glomerular filtration rate (Cockcroft-Gault Equation) (GFR-CG) at baseline was the strongest age-adjusted predictor of major bleeding (Wald Chi-Square: 31.84; p Conclusion Bleeding events on therapy with edoxaban can be predicted by quantifying kidney disease and capturing information on heart failure, frailty, prior bleeding, chronic obstructive lung disease and history of myocardial infarction. These data highlight the need for optimal management of anticoagulation therapy and close follow-up of patients with such risk profiles. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH Figure 1. GFR-CG as a predictor of major bleedingFigure 2. Predictors of major bleeding

Background Oral anticoagulation is highly effective in preventing ischaemic stroke in patients with atrial fibrillation, but 1–2% of the patients suffer an ischaemic stroke upon anticoagulation. Outcomes are further influenced by various factors, and recent research has focussed on identifying risk factors that could be helpful in predicting stroke outcomes in anticoagulated patients. This could further assist clinicians in timely identification and management of high-risk patients. Purpose The present analysis aims to assess the age-adjusted risk predictors of ischaemic stroke and systemic embolic events (SEE) (including transient ischaemic attack [TIA]) during two-year follow-up of unselected European patients with AF in the ETNA-AF-Europe registry. Methods ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational study conducted in 825 centres enrolling patients treated with edoxaban once daily in 10 European countries. Wald Chi square tested the association between risk predictors and stroke and SEE after adjusting for age, given that age is a well-known, strong predictor of stroke. Results A total of 13,417 patients with AF (edoxaban 60 mg: n=10,248; edoxaban 30 mg: n=3169) completed the two-year follow-up. The mean age was 73.6±9.5 years, with ∼84% of the patients aged over 65 years. The mean weight was 81.0±17.3 kg, estimated glomerular filtration rate was 74.4±30.5 ml/min/1.73m2 and males were 56.6%. The mean CHA2DS2-VASc and HAS-BLED scores were 3.2 and 2.5, respectively. Univariate analysis demonstrated that history of TIA at baseline was the strongest age-adjusted predictor of stroke and SEE (Wald Chi-square: 77.69; p Conclusion History of TIA, CHA2DS2-VASc score, history of stroke, frailty and HAS-BLED score are independently associated with an increased age-adjusted risk of ischaemic stroke, TIA and SEE in anticoagulated patients with AF. These findings highlight the importance of optimising anticoagulation therapy in secondary prevention of TIA and in patients with high CHA2DS2-VASc scores, ensuring the correct use of NOACs - adherence and correct dosing - in this high-risk population. These findings also suggest that additional therapies could be needed to prevent stroke in this population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH Figure 1. History of TIA as a predictorFigure 2. CHA2DS2-VASc score as a predictor

Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) coexist in many patients. AF and HFpEF are closely intertwined, but there are important knowledge gaps in the pathogenesis, risk, prevention and treatment of AF with concomitant HFpEF, in particular with respect to reversal of HFpEF signs. Purpose To assess the proportion of AF patients with (any) HFpEF criteria (including patients with heart failure with moderately reduced ejection fraction (HFmrEF)) who – after successful AF ablation – no longer meet the criteria for HFpEF on neurohumoral and echocardiographic level. Furthermore, to assess whether normalisation of HFpEF criteria positively affects AF recurrence. Methods Patients (n=526) underwent thoracoscopic AF ablation, consisting of pulmonary vein isolation (PVI) alone or PVI with additional lines in the case of persistent AF and were prospectively followed-up. Patients (n=338) with a left ventricular ejection fraction (LVEF) ≥40% and a successful ablation at 6 months follow-up, that is freedom of AF, or any atrial tachycardia of more than 30 seconds, were included in this study. Participants were grouped based on N-terminal pro-b type natriuretic peptide (NT-proBNP) into those with a NT-proBNP Results In total, 69% of AF patients (with a preserved ejection fraction of ≥40%) fulfilled the criteria for HFpEF. In 23% of these patients, neurohumoral levels normalised after elimination of AF, and a normalisation of echocardiographic markers was seen in 58% of patients. Normalisation of HFpEF on a neurohumoral level was associated with numerically fewer AF recurrence at 1 year follow-up (23% versus 33% in patients with and without NT-proBNP Conclusion In AF patients with definite restoration of sinus rhythm HFpEF may be reversed. This suggests that neurohumoral and echographic changes are caused by AF rather than by HFpEF. Normalisation of neurohumoral changes after definite restoration of sinus rhythm led to better outcome with regards to AF-recurrence, which could be used in prediction of prognosis. Funding Acknowledgement Type of funding sources: None.

Background There is an increasing number of smartwatches and devices commercially available that can generate and automatically interpret an electrocardiogram (ECG). Such devices have an enormous potential to improve population screening and telemonitoring of atrial fibrillation (AF). Purpose There is limited data on the sensitivity, specificity and interpretability of these devices and comparative studies are lacking. Our purpose was to compare three frequently used devices for AF detection. Methods We performed a single-center, prospective study in consecutive patients with AF presenting for electrical cardioversion (ECV). We collected a standard 12-lead ECG recording immediately followed by four times 30 seconds of ECG recordings from different devices for every patient prior to the ECV. These paired measurements were considered simultaneous. If the ECV was performed, the same measurements were repeated afterwards. The standard 12L-ECGs were interpreted by a cardiologist and used as golden standard for heart rhythm. The different devices used for the 30 second ECGs were: Withings Move ECG (lead I), Apple Watch series 5 (lead I), Kardia Mobile 6L (six leads) and Withings/Apple (1:1 ratio) on left knee (lead II). Sensitivity and specificity were determined for each AF detection algorithm excluding patients with atrial flutter (AFL) or uninterpretable ECGs. In addition, proportions of uninterpretable ECGs were determined including all patients and including only patients with sinus rhythm (SR) and compared between devices using McNemar's test. Results A total of 220 patients were included (age 70±10 years, female 35%, first ECV 44%) and in total 415 12-lead ECGs were performed (45% SR, 45% AF, 10% AFL). The sensitivity/specificity were overall similar for all devices (Withings 98%/95%, Apple 94%/98%, Kardia 99%/91%. P>0.05 for all). In detail, Kardia was the most sensitive test with highest proportion of suspected AF (57%) whereas Apple was the most specific, as shown by the highest proportion of normal heart rate results by the device (55%, P=0.003 compared to Kardia (43%)). Overall, Withings, Apple and Kardia had a comparable proportion of uninterpretable ECGs (20%, 20%, 24%, respectively. P>0.05 for all). Lead II had higher proportion of uninterpretable ECGs (32%, p Conclusion In all devices, we found sensitivity/specificity for AF detection between 91%-99%, better than previous studies reported, and 20–24% of uninterpretable ECGs. Kardia was the most sensitive device, but less useful to rule out atrial fibrillation whereas Apple had numerically highest specificity. We aim to further evaluate both cardiologist interpretation and accuracy of atrial flutter detection using different leads to inform clinical use. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Tergooi Cardiology department, J.P. Bokma was supported with a research grant by Amsterdam Cardiovascular Sciences Overview and comparison

Background Use of vitamin K antagonists (VKAs) is associated with a crude event rate of 23% per year for worsening renal function (WRF). Although non-vitamin K antagonist oral anticoagulants (NOACs) have been associated with a lower risk of longitudinal decline in renal function compared with VKAs, available evidence on renal function decline in patients using NOACs is still limited. Furthermore, renal function is a dose reduction criterion for NOACs, which poses an important question about how physicians should treat patients whose renal function worsens over time. Purpose To evaluate the degree of renal function decline in AF patients treated with edoxaban after 2 years of follow-up, and to investigate clinical outcomes of patients with vs without WRF in the ETNA-AF-Europe study. Methods ETNA-AF-Europe is a multinational, multicentre, observational, post-authorisation safety study conducted in 825 sites in 10 European countries. Results are based on a data snapshot taken on 26th October 2020 which include data up to 2 years of follow-up. Patients were excluded from the analysis population if data to calculate estimated glomerular filtration rate [eGFR] were not available for at least one of the follow-up time-points of 1-year and 2-year. We categorised patients (n=9084) into two subgroups: 1) those with WRF (i.e. ≥25% decline in eGFR from baseline; n=918), and 2) those without WRF (n=8166). eGFR was estimated using the Cockcroft-Gault formula. Baseline characteristics and annualised event rates including 95% confidence intervals were analysed using descriptive analyses. Results Of the 13,417 patients in ETNA-AF-Europe who were included in the 2-year follow-up analysis, 9084 were included in this subgroup analysis, of whom 56.2% were male. Baseline eGFR were similar between patients with and without WRF when comparing across the different renal function categories (Table 1). The majority of the edoxaban-treated patients did not experience WRF (89.9%) during the 2 years of follow-up. The proportion of patients with WRF (10.1%) were older, more often frail and had higher rates of underlying comorbidities, such as diabetes, hypertension and heart failure (Table 1). Patients with WRF had higher annualised event rates of all-cause and cardiovascular death than those without (3.78% vs 1.90% and 2.06% vs 0.92%, respectively). Major bleeding and stroke rates were low, but numerically higher in patients with renal worsening compared to those without WRF (Figure 1). Intracranial haemorrhage rates remained low (0.17% vs 0.19%; Figure 1) in both subgroups. Conclusions This subgroup analysis provides real-world evidence for a low risk of WRF in AF patients treated with edoxaban over a 2-year period. Patients with WRF had higher mortality than those without, as well as numerically higher major bleeding and stroke rates. Importantly, intracranial haemorrhage rates remained low irrespective of WRF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH /

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe OnBehalf ETNA-AF-Europe investigators Background Oral anticoagulation (OAC) for stroke prevention is essential in the management of patients with atrial fibrillation (AF). The assessment of OAC use in routine clinical care and the effects of this therapy on outcomes and safety are important. Purpose: We analysed two-year outcome data with adjudicated follow-up results in 13,417 patients with AF treated with edoxaban. Methods: ETNA-AF-Europe (Clinicaltrials.gov: NCT02944019) enrolled 13,417 consecutive patients with AF treated with edoxaban in 825 centres in 10 European countries and 2-year prospectively collected, real world data is presented. Results: Edoxaban was prescribed according to licence recommendations in 83.1% (n = 11,146) of patients (Table). Whilst three quarters of patients were prescribed edoxaban 60 mg (n = 10,248, 76.4%), the quarter prescribed edoxaban 30 mg were older (79.5 versus 71.8 years), had a higher stroke risk (CHA2DS2-VASc score: 3.9 versus 3.0) and a higher bleeding risk (HAS-BLED score: 2.9 versus 2.4). Thromboembolic and bleeding events were more common in patients receiving edoxaban 30 mg OD without differences in intracranial haemorrhage (ICH) (Figure). Patients prescribed a non-recommended dose of edoxaban had a numerically higher stroke risk (CHA2DS2-VASc score: 3.6 versus 3.1) with subsequent higher rates of ischemic stroke and mortality, however they also had higher bleeding rates, with the exception of ICH (table) despite a similar initial bleeding risk (HAS-BLED score: 2.7 versus 2.5). Conclusions: In this large, European data set reporting two-year outcomes on edoxaban therapy, no additional safety signals were observed and event rates were in line with those observed in ETNA-AF after 1 year and in ENGAGE AF-TIMI 48, re-affirming the safety and effectiveness of edoxaban licence recommendations in a real world setting of patients with AF. All key events of interest, other than intracranial haemorrhage, were numerically lower in patients prescribed the licenced recommended dose. Outcomes with rec. vs non-rec. dosesn (%/year [95%CI])Recommended dose (n = 11,146; 83.1%)Non-recommended dose (n = 2271; 16.9%)Any stroke/SEE138 (0.68 [0.57;0.80])31 (0.76 [0.51;1.07])Ischaemic stroke99 (0.48 [0.39;0.59])26 (0.63 [0.41; 0.93])Major bleeding189 (0.93 [0.80;1.07])49 (1.20 [0.89;1.59])Intracranial haemorrhage43 (0.21 [0.15;0.28])7 (0.17 [0.07;0.35])All-cause mortality729 (3.55 [3.30;3.82])208 (5.04 [4.38;5.78])CV mortality405 (1.97 [1.79;2.18])113 (2.74 [2.26;3.30])CI, confidence interval; CV, cardiovascular; rec., recommended; SEE, systemic embolic event.Abstract Figure. Annualised event rates at 2-year FU

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe OnBehalf ETNA-AF-Europe investigators Background Coronary (CAD) and peripheral artery disease (PAD) are common comorbidities in patients with atrial fibrillation (AF). Such concomitant vascular disease may affect the effectiveness and safety of treatment with edoxaban, but data from daily practice are limited. Purpose: To determine the incidence of ischaemic and bleeding events in edoxaban-treated AF patients with CAD/PAD, and to assess whether the effect of edoxaban might be influenced by concomitant vascular disease. Methods: With 1-year follow-up data from ETNA-AF-Europe, clinical characteristics and frequencies of adverse events were compared between AF-patients with and without CAD/PAD. Results: Of 13,089 patients, 2956 had vascular disease (n = 2738; 92.6% had CAD). Patients with CAD/PAD were older, had lower creatinine clearance, higher stroke and bleeding risk scores, and were more frequently prescribed the reduced dose of edoxaban than those without these comorbidities (Table). Rates of stroke/systemic embolism (0.99 vs 0.77%/year), and major bleeding (1.28 vs 0.98%/year) were numerically higher in patients with CAD/PAD than in those without. Myocardial infarction (1.31 vs 0.30%/year), cardiovascular deaths (2.33 vs 1.43%/year) as well as all-cause deaths (5.18 vs 3.01%/year) occurred significantly more often in the CAD/PAD subgroup (Figure). Conclusions: Rates of ischaemic and bleeding events are low in unselected edoxaban-treated AF patients, regardless of the presence/absence of concomitant vascular disease. The higher rates of myocardial infarction and (non-)cardiovascular death in the CAD/PAD subgroup are thought to be largely unrelated to differences in the effect of edoxaban, but attributable to the differences in baseline intrinsic risks instead. Nonetheless, these differences warrant further investigation. Baseline characteristics n (%) or Mean ± SDPatients with CAD and/or PADPatients without CAD and/or PADTotal (N = 2956)Edoxaban 60 mg (n = 2044)Edoxaban 30 mg (n = 915)Total (N = 10,133)Edoxaban 60 mg (n = 7947)Edoxaban 30 (n = 2186)Male2115 (71.5)1541 (75.4)574 (62.7)5315 (52.5)4520 (56.9)795 (36.4)Age, years75.3 ± 8.573.4 ± 8.279.4 ± 7.673.1 ± 9.771.4 ± 9.379.6 ± 8.1Body mass index, kg/m²28.1 ± 4.728.6 ± 4.727.0 ± 4.728.1 ± 5.228.6 ± 5.226.3 ± 5.1eGFR,* mL/min/1.73m²69.3 ± 28.378.2 ± 27.450.7 ± 19.875.7 ± 30.983.2 ± 29.650.1 ± 19.5(calc.)CHA2DS2-VASc3.5 ± 1.43.3 ± 1.44.0 ± 1.43.0 ± 1.42.8 ± 1.33.7 ± 1.2(calc.) mod. HAS-BLED†2.9 ± 1.12.8 ± 1.13.3 ± 1.12.4 ± 1.12.3 ± 1.12.8 ± 1.0Frailty‡391 (13.2)159 (7.8)232 (25.4)1001 (9.9)453 (5.7)548 (25.1)Data are presented as mean ± standard deviation for continuous variables or n (%) for categorical variables. *Glomerular filtration rate (GFR) was estimated by Cockcroft-Gault formula. †Not including labile international normalised ratio. ‡It was left to the physician"s discretion to categorise a patient as frail.Abstract Figure. One-year outcomes

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe OnBehalf ETNA-AF-Europe investigators Background Valvular heart disease (VHD) is a common comorbidity in patients with atrial fibrillation (AF); the optimal anticoagulant treatment of such patients remains largely unexplored. Purpose: To evaluate differences in the baseline characteristics and 1-year event profiles of edoxaban-treated AF patients with or without VHD. Methods: ETNA-AF-Europe prospectively enrolled 13,980 patients with AF from 825 centres in 10 European countries. Baseline characteristics and 1-year annualised event rates for edoxaban-treated AF patients with or without VHD were compared using descriptive analyses. VHD was defined as reported by investigator. Results: Of the 13,092 AF patients who completed the 1-year of follow-up, 2,314 patients had VHD and 10,778 did not have VHD at baseline. Patients with VHD were older, had lower body weight and worse renal function, a higher stroke score, and were considered more frail by their physician than patients without VHD (Table). Patients with VHD had higher annualised event rates of all-cause mortality, stroke or systemic embolic events and bleeding events than those without VHD (Figure). However, rates of intracranial haemorrhage and myocardial infarction were similar between those with and without VHD. Conclusions: Patients with or without VHD had low rates of adverse events on receiving edoxaban treatment. Patients with VHD had more comorbidities at baseline and a higher risk of mortality, major bleeding and stroke but not of ICH versus those without VHD after 1 year of treatment. Baseline characteristicsOverall (n = 13,092)Patients with VHD (n = 2314)Patients without VHD (n = 10,778)Male, n (%)7430 (56.8)1245 (53.8)6185 (57.4)Age (years), mean ± SD73.6 ± 9.575.9 ± 8.673.1 ± 9.6Body weight (kg), mean ± SD81.0 ± 17.378.0 ± 15.981.6 ± 17.5CrCl (Cockcroft-Gault) (mL/min), mean ± SD74.3 ± 30.466.0 ± 26.476.0 ± 30.9CHA2DS2-VASc, mean ± SD3.1 ± 1.43.5 ± 1.33.0 ± 1.4Modified HAS-BLED, mean ± SD2.5 ± 1.12.8 ± 1.12.4 ± 1.1Frailty, n (%)1392 (10.6)381 (16.5)1011 (9.4)Current AF type Paroxysmal Persistent Long-standing persistent & permanent7039 (53.9)3159 (24.2)2864 (21.9)1083 (46.9)578 (25.0)648 (28.0)5956 (55.4)2581 (24.0)2216 (20.6)*Frailty was subjectively assessed as perceived by the investigator. AF, atrial fibrillation; CrCl, creatinine clearance; OD, once daily; SD, standard deviation; VHD, valvular heart disease.Abstract Figure. One-year outcomes

Sometimes there is doubt as to whether or not anticoagulants should be initiated, and if so which ones, in patients with atrial fibrillation and advanced age, increased frailty, or fall risk, kidney, or liver impairment, alcohol abuse, uncontrolled hypertension, or a history of major bleeding. These subgroups have increased risk of haemorrhage as well as thromboembolism. Treatment with anticoagulants is indicated in the vital elderly, preferably with direct oral anticoagulants as demonstrated by robust data. The available study results for the other subgroups may not be (fully) generalisable to clinical practice. In such patients, a comprehensive risk assessment is therefore advised; as is discussing the pros and cons of (not) using anticoagulants and of both type of anticoagulants. Only in exceptional cases is it justified not to use anticoagulants.

Background Ablation therapy is widely used as a treatment of atrial fibrillation (AF) and is associated with 3.6% minor and major complications in the Netherlands. Mortality following AF ablation is rare, but has been reported 0.46% in the United States in recent literature. We hypothesize that in the Netherlands, where AF ablation is performed in high volume centres only, 30-day mortality rate is low. Purpose To describe 30-day mortality in the Netherlands after AF ablation. Methods In the Netherlands Heart Registration, all 16 Dutch ablation centres participate and 14 out of 16 centres reported AF ablation outcomes using predefined variables for quality purposes. The number of reported procedures per centre was on average 236/year [range, 33–593], where 87.5% of the centres perform >150 AF ablations per year. All patients who underwent AF ablation were eligible for this analysis irrespective of ablation method used, or whether it was the first or a redo AF ablation. 30-day mortality was derived from, the municipal death registration, and individually checked by each participating ablation centre. No further analysis was available on the cause of death. Results In total, 20,230 patients who underwent AF ablation between 01-01-2013 and 31-12-2018 were included. The majority of patients were male (68%), mean age was 60.9±9.8 years, mean body mass index was 27.3±4.2kg/m2, and the average CHA2DS2VASc score was 1.6±1.3. Reduced left ventricular (LV) ejection fraction ( Conclusion Patients undergoing AF ablation in the Netherlands mainly presented with paroxysmal AF. In a setting where AF ablation is performed in high volume centres only, such as the Netherlands, 30-day mortality is very low after AF ablation. Funding Acknowledgement Type of funding source: None

Introduction Postoperative atrial fibrillation (POAF) occurs in up to 45% of patients following cardiothoracic surgery and is defined as any atrial tachyarrhythmia occurring ≤30 days after surgery. Consequently, atrial arrhythmias after 30 days are regarded as new-onset AF. However, biological and clinical data on the association between POAF and new-onset AF, or empirical data supporting the cut-off of 30 days, are lacking. Purpose We hypothesize that patients with POAF are biologically different with respect to atrial fibrosis compared to patients who develop new-onset AF. Methods PREDICT AF is a prospective, multicenter, observational trial that included patients with a CHA2DS2VAsc score≥2 without a history of AF. Patients underwent CABG or valve surgery and the left atrial appendage (LAA) was removed during surgery. The LAA was obtained for expression analysis of extracellular matrix (ECM) genes such as collagen 1 (COL1A1), collagen 3 (COL3A1) and fibronectin (FN1) by qPCR. Patients were monitored during hospitalisation and followed-up at 1, 6, 12 and 24 months with 24-h Holters and ECGs. The primary endpoint was any recorded atrial tachyarrhythmia lasting >30 seconds. We documented all new-onset arrhythmias over time in order to determine potential cut-offs for POAF (Figure A). We then compared the effects of using a 30-, 50- or 70-day cut-off on the rate of new-onset AF and the differences in expression of fibrosis related genes. Results PREDICT AF included 150 cardiac surgery patients: 115 CABG, 11 valve surgeries and 24 combined surgeries. Participants had a median follow-up of 1.9 years [1.0–2.0], were 68±7 years old and 19 (13%) were female. POAF 30 days developed in 21 (14%) patients. Of the 21 patients with new-onset AF, 20 (95%) also had had POAF. New-onset AF defined by a cut-off of 50 days, developed in 15 (10%) patients. In total, 9 patients had an episode of AF between 30 and 50 days, of whom 6 (66.6%) had no AF episodes thereafter. Most of these patients under–went (concomitant) aortic valve surgery. The gene expression of ECM components was significantly more predictive of new-onset AF when using a cut-off of 50 days or even 70 days than when using a cut-off of 30 days (Figure B). Conclusion With stringent monitoring we detected 42% POAF New-onset AF prediction with ECM genes Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NWO VIDI

Contains fulltext : 225355.pdf (Publisher’s version ) (Open Access) In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies.

Background: Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. Methods: The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. Results: In total, 225 adults (mean age 54 ± 15 years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54–80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc ≥ 1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n = 15) could not be demonstrated. Conclusions: The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc ≥ 1 or Fontan circulation.

BACKGROUND: Monosodium glutamate (MSG), also referred to as Vetsin or E621, is a flavour enhancer frequently used in Asian cuisine and abundantly present in the famous Chinese dish Peking duck. MSG is notorious for triggering the onset of the so-called 'Chinese restaurant syndrome' (CRS), a complex of unpleasant symptoms, which might include flushing, sweating and the onset of atrial fibrillation (AF). This study aims to determine the effects of MSG on the occurrence of AF. METHODS: We conducted a placebo self-controlled single-arm study in the Academic Medical Centre in Amsterdam. We included paroxysmal AF patients who reported a consistent onset of AF upon MSG intake. During three admissions, participants were subsequently administered: placebo, 1.5 g and 3 g MSG. If AF was recorded after the dose of 1.5 g MSG, patients were given another placebo instead of 3 g MSG. The primary outcome was the onset of AF registered by 24-hour Holter monitoring. The secondary outcomes were any other arrhythmia and the onset of CRS defined as two or more symptoms of CRS after MSG intake. RESULTS: Six men participated in the study. Both 1.5 g and 3 g MSG were unrelated to CRS, arrhythmias or AF occurrence. CONCLUSION: Peking duck can be put on the Christmas menu without risking guests to be admitted to the emergency department with new episodes of AF.

Despite advances in therapeutic interventions AF remains a progressive and symptomatic disease. Therefore, novel therapeutic interventions targeting the underlying arrhythmogenic substrate for AF is needed. Atrial fibrosis is an important component of the arrhythmogenic substrate of AF and may be initiated by aldosterone binding to the mineralocorticoid receptor. We hypothesized that aldosterone pathway blockade with mineralocorticoid receptor antagonists (MRA) reduces atrial fibrosis, and thus AF. We searched OVID MEDLINE, OVID EMBASE and the Cochrane Central Register of Controlled Trials from inception to June 10th, 2016 for randomized controlled trials (RCT) and observational studies addressing MRA and providing information on AF occurrence. Two independent reviewers selected and appraised the data. We performed random-effects meta-analyses. Summary odds ratios (OR) with 95% confidence intervals (CI) were calculated. We included 14 studies, 5 RCT and 9 observational cohorts, with a cumulative number of 5332 patients (male: 74.9%, age: 65.3years); 2397 (45.0%) received an MRA (spironolactone or eplerenone). During follow-up, 204 (8.5%) patients treated with MRAs, developed AF, compared to 547 (18.6%) patients, without MRA treatment. Meta-analyses showed a significant overall reduction of AF risk in MRA treated patients (OR: 0.48 CI: 0.38-0.60 p

Background Atrial fibrosis is a hallmark of atrial fibrillation (AF) and serves as an important arrhythmogenic substrate. It is formed by fibroblasts in response to tissue dyshomeostasis induced by multiple factors such as ageing, hypertension and inflammation. How fibroblasts phenotypically transform into an active form with enhanced profibrotic capacity in AF pathophysiology remains elusive. The primary cilium is an antenna-like small organelle, that function as a sensor to transduce external stimuli to intracellular signaling thereby potentially mediating the fibroblast's profibrotic capacity. Their involvement in AF pathophysiology is not known. Objective To explore the role of fibroblasts' primary cilium in the formation of the atrial fibrosis in AF. Methods Left atrial appendages (LAA) were obtained from persistent AF patients (AF: n=10) and patients without AF undergoing cardiac surgery (control: n=10). Primary cilia were immunostained with anti-acetylated a-tubulin in cryosections of the LAA. The loss of cilia in fibroblasts isolated from fresh LAA (AF: n=3, control: n=3) was induced by RNAi targeting IFT88, an essential factor for cilia formation. Gene expression and protein levels in LAA were quantified by qPCR and western blot, respectively (AF: n=20, control: n=20). Results The ratio of fibroblasts with primary cilium was significantly decreased in LAA of AF cohort (AF: 14.7%±4.6 vs control: 25.9%±3.6, p Primary cilium is disassembled along with degradation of acetylated a-tubulin by HDAC6. Indeed, a negative correlation between the protein levels of acetylated a-tubulin and HDAC6 were observed in the LAA of AF cohort (p Conclusion The formation of primary cilia in fibroblasts is actively suppressed in AF via HEF1/AURKA/HDAC6 cascade, which in turn enhances the profibrotic response of fibroblasts. This study provides an innovative paradigm for fibrosis formation in AF, and implicates that the primary cilium of fibroblasts potentially become a novel therapeutic target to treat the AF substrate.

Background Severely enlarged left atrial (LA) volume is associated with a considerable ineffective outcome of ablation for atrial fibrillation (AF). Therefore, in patients with AF and a giant atrial volume catheter ablation is not recommended. However, thoracoscopic AF ablation is being performed in patients with AF and giant LA, but with unknown efficacy. Purpose To determine efficacy of thoracoscopic AF ablation in patients with AF and a giant LA. Methods Patients underwent thoracoscopic AF ablation (paroxysmal AF) plus additional left atrial ablations (persistent AF) and were prospectively followed. Giant LA was defined as left atrial volume index (LAVI)≥50 ml/m2, outcome was also assessed for LAVI≥55 ml/m2. Follow-up was performed with ECGs and 24-hour Holters every three months. After a 3-month blanking period, all AADs were discontinued. Primary outcome was recurrence of any atrial tachycardia ≥30 sec during one year of follow-up. Results Between 2008–2017, 357 patients underwent thoracoscopic AF ablation. At baseline, giant LA was diagnosed in 72 (20.2%) patients (mean LAVI: 59.5±9.6 ml/m2), while 285 (79.8%) had a smaller left atrium (mean LAVI: 36.3±7.8 ml/m2), p Kaplan-Meier analysis of AF recurrence i Conclusion Thoracoscopic AF ablation is an effective therapy in patients with a giant LA. Thoracoscopic AF ablation may therefore be a feasible treatment for patients with a giant LA.

Introduction Edoxaban has been approved for stroke prevention in patients with atrial fibrillation based on its comparable efficacy and superior safety compared to warfarin in the pivotal ENGAGE AF-TIMI 48 trial. ETNA-AF Europe (NCT02944019) was initiated in agreement with the EMA to evaluate benefits and risks of edoxaban treatment in unselected patients in routine clinical practice. Methods 13,980 patients from across 825 hospital and office-based physicians from 10 European countries (Austria, Belgium, Germany, Ireland, Italy, The Netherlands, Portugal, Spain, Switzerland and United Kingdom) were enrolled, and will be followed-up for 4 years. This snapshot analysis includes baseline and first outcome data of 7,672 patients (56.3% of all enrolled patients) that have completed their first 1-year follow-up visit (mean follow-up: 343.5 days). Results The average age of patients was 73.4 years, the mean weight was 81.9 kg (Table 1). Frequent comorbidities include hypertension (77.2%), valvular heart disease (17.4%), congestive heart failure (5.8%) and history of myocardial infarction (4.2%). Patients receiving the 30 mg dose (22.9%) were older, had a lower creatinine clearance and had a higher risk for both stroke and bleeding as compared to those on the 60 mg dose (77.1%). Overall, the incidence of clinical events was low: all-cause mortality: 3.56%/y, major bleeding 0.95%/y, intracranial haemorrhage 0.28%/y, any stroke or systemic embolic events 0.88%/y. Patient characteristics at Year 1 Patient characteristics All patients Edoxaban 60 mg Edoxaban 30 mg [7,672] [5,916 (77.1%)] [1,756 (22.9%)] Age [years] mean (SD) 73.4 (9.26) 71.8 (8.98) 79.1 (7.81) Body weight [kg] mean (SD) 81.9 (17.33) 84.1 (16.80) 74.3 (16.93) CrCl (CG) [mL/min] mean (SD) 75.0 (30.29) 82.5 (29.14) 51.2 (19.75) CHA2DS2-VASc mean (SD) 3.1 (1.38) 2.9 (1.34) 3.8 (1.28) HAS-BLED mean (SD) 2.5 (1.10) 2.4 (1.07) 2.9 (1.08) First occurrence of all-cause mortality (n, %/year) 257 (3.56%) 129 (2.31%) 128 (7.90%) First occurrence of intracranial haemorrhage (n, %/year) 20 (0.28%) 16 (0.29%) 4 (0.25%) First occurrence of major bleeding (n, %/year) 68 (0.95%) 49 (0.88%) 19 (1.18%) First occurrence of stroke/SEE (n, %/year) 63 (0.88%) 45 (0.81%) 18 (1.11%) CG, Cockcroft-Gault; CrCl, creatinine clearance; SD, standard deviation; SEE, systemic embolic events. Conclusions We found low bleeding and stroke rates in 7,672 unselected, mainly elderly AF patients treated with edoxaban in routine clinical practice. These findings were consistent across edoxaban doses and reinforce the effectiveness and safety of NOACs such as edoxaban in routine clinical care in Europe. Acknowledgement/Funding Daiichi Sankyo Europe GmbH, Munich, Germany

Purpose To evaluate the proportion of patients in whom parameters that define the diagnosis of HFpEF and HFmrEF persist versus normalize upon elimination of AF. Background Atrial fibrillation (AF) and heart failure with preserved or mid-range ejection fraction (HFpEF or HFmrEF) concur in many patients. Distinction between these two diagnoses remains challenging as one can cause or exacerbate the other. Adequate patient selection for invasive AF treatment is crucial to improve rhythm outcome. Methods Patients underwent thoracoscopic ablation, consisting of pulmonary vein isolation (PVI) alone or PVI with additional lines in the case of persistent AF. Patients were prospectively followed-up. HFmrEF or HFpEF was defined as left ventricular ejection fraction (LVEF) ≥40% or ≥50% respectively and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels >125 pg/ml. Patients who remained free from AF, or any atrial tachycardia of more than 30 seconds, at 6 months postoperatively, were included in this study. Patients with AF recurrences during this period were excluded. The primary outcome was the change of NT-proBNP at 6 month follow-up. Results From 2008 to 2017, 92 patients undergoing thoracoscopic AF ablation fulfilled the aforementioned criteria and were included. Of these patients, mean age was 61±8 years and 66 (72%) were male. Median NT-proBNP was 366 pg/ml (128–2916) and mean LVEF was 53±7%. Thirty (35%) patients had a LVEF of 40–49%. Six months after elimination of AF, NT-proBNP was Figure 1. NT-proBNP alterations after thoracoscopic AF ablation from baseline to 6 month follow-up. A. Patients with normalization of NT-proBNP. B. Patients with unchanged high levels of NT-proBNP. Conclusion In 28% of patients the diagnostic criteria of HFpEF/HFmrEF are caused by AF and normalize upon elimination of AF with thoracoscopic ablation.

Introduction Pulmonary vein isolation (PVI) has become a cornerstone of the treatment of atrial fibrillation (AF). Several technologies have been developed to improve procedural and long-term outcomes. Depending on type of AF and rhythm recording used, 1-year freedom of AF varies between 55–82%. However, severe complications are reported in 1–3%. Purpose To describe procedural complications of PVI with either single tip radiofrequency ablation (STRF), multi electrode phased RF ablation (PVAC) or cryoballoon (CB). Methods Data was extracted from the Netherlands Heart Registry in which 14 Dutch heart centres participate. Procedural complications in patients treated with the 3 different ablation modalities (STRF, PVAC and CB ablation) were compared. Complications included: pericardial tamponade, persistent phrenic nerve palsy (PNP) beyond 24hrs, thromboembolic events, vascular- and bleeding complications. Patient characteristics: gender, age, BMI, CHA2DS2 -VASc, type of AF and previous left atrium ablation were assessed in a univariate and multivariate regression model. Results In total, 12,430 patients were included (STRF n=5,106, PVAC n=2,341, CB n=4,983) between January 2013 and December 2017, of whom, 69% were male, 74% had a history of paroxysmal AF, 24% persistent AF and 2% longstanding persistent AF. The incidence of complications within 30 days was 3.6%. Pericardial tamponade requiring intervention, occurred more frequently in the STRF group (STRF: 0.8% vs PVAC 0.3% vs CB 0.3% p= Univariate analysis Conclusion PVI was associated with a complication rate of 3.6%. Compared to PVAC and CB ablation, patients treated with STRF ablation more often developed a pericardial tamponade and vascular- and bleeding complications. PNP occurred most frequent in patients undergoing CB ablation. Female gender and CHA2DS2-VASc were independent predictors for pericardial tamponade, vascular- and bleeding complications.

Background Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have substantially improved anticoagulation therapy for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF), and available routine care data have so far broadly confirmed the safety of different NOACs in routine practice. However, such data for edoxaban are scarce, especially in extremely low and high body weight (BW). These extreme BWs may affect the bioavailability, distribution, and half-life of NOACs and, consequently, outcomes of treatment. Methods We analysed outcomes in normal-weight (BMI 18.5–25) vs overweight (BMI 25–30) and obese (BMI >30) patients enrolled into the ETNA-AF-Europe observational study (NCT02944019) collecting information on patients treated with edoxaban in 825 sites in 10 European countries. This snapshot analysis set includes data of 7,672 patients (56.3% of all enrolled patients) which have completed their 1-year follow-up visit (mean follow-up: 343.5 days). Results Median patient age was 74 years for all patients, 76 years for patients with a BMI 18.5–25 (group 1), 75 years for patients with BMI 25–30 (group 2), and 72 for patients with a BMI >30 (group 3). CrCl was 64 mL/min for patients with a BMI 18.5–25, 68 mL/min for patients with BMI 25–30, and 72 mL/min for patients with a BMI >30. The CHA2DS2-VASc (mean 3.1±1.38) and HAS-BLED (mean 2.5±1.10) score did not differ significantly between groups. As expected, diabetes and hypertension were significantly less prevalent in leaner patients and - accordingly - inversely correlated to age. There was no correlation between body weight and life-threatening bleeding (group 1: 0.28%; group 2: 0.40%; group 3: 0.14%). Also, stroke rates (group 1: 0.74%; group 2: 0.81%; group 3: 0.76%) did not differ between groups. Conclusion BMI, within the range here assessed, does not affect 1-year outcomes in European AF patients treated with edoxaban. Acknowledgement/Funding Daiichi Sankyo Europe GmbH, Munich, Germany

Background The electrocardiogram (ECG) is commonly used, but most recent rhythm discrimination algorithms still lack both specificity and sensitivity. Deep learning techniques have shown promising results in the classification of physiological signals like ECGs. Purpose To develop and test a deep learning (DL) model to discriminate between atrial fibrillation (AF) and sinus rhythm (SR). Methods For the development of the DL model we used 1499 ECGs sampled at 500 Hz of patients diagnosed with AF. All ECGs were labeled by two experienced investigators. Only ECGs labeled as SR or AF were included in the dataset. To simplify the learning process, solely the first ECG channel was used. The ECG waveforms were preprocessed using the Fourier cosine series to correct for baseline wander. Input data was generated by normalizing and scaling all different heartbeats by centralizing the R peak, leading to 15744 single heart beat samples of 80 data points (figure A). Multiple feedforward architectures were tested with different numbers of layers, filters and activation functions. The models were trained by equally splitting the data (50%SR, 50%AF) in a training (65%), validation (25%) and test set (15%). The best performing model was chosen based on the accuracy. Results A total of 1469 ECGs (1061 (72%)SR, 408 (28%)AF) were included. The model with the best performance was a feedforward model consisting three dense layers with ReLU activation and four dense layers with Linear activation. Training of the model was performed in 32 epochs. Validation of the model resulted in an accuracy of 96% (figure B), precision of 95% and recall of 96%. Conclusions The morphology based deep learning model developed in this study was able to discriminate atrial fibrillation from sinus rhythm with a fairly high accuracy using a limited size dataset and only one lead.

Background Edoxaban, a direct FXa inhibitor, has been proven non-inferior in efficacy and safer compared to warfarin in the ENGAGE AF-TIMI 48 trial. In routine care, the safety of edoxaban has not been formally established. ETNA-AF-Europe is a multinational, multi-centre, post-authorisation, observational study (NCT02944019) conducted in 825 sites in 10 European countries. Here 13,980 edoxaban-treated patients with AF were enrolled between November 2016 and February 2018, and will be followed-up for 4 years. Methods 7,672 patients (73.4±9.26 years, 57.5% male) enrolled in the ETNA-AF Europe registry completed the one-year follow-up and were stratified into low-, intermediate- and high-risk for stroke and bleeding using the CHA2DS2-VASc and HASBLED score, respectively. We here analysed the occurrence of stroke, bleeding, intracranial haemorrhage and mortality in such categories. Results The mean CHA2DS2-VASc score at baseline was 3.1±1.38 and the mean HAS-BLED score was 2.5±1.1. Not surprisingly, patients at higher risk were older, had a lower body weight, more comorbidities, and a lower creatinine clearance. A higher proportion of patients at high risk received the reduced 30 mg edoxaban dose. Overall, the yearly event rates of stroke, intracranial haemorrhage, major bleeding and death were low. However, these rates increased consistently in patients with higher stroke and bleeding risks. Residual stroke risk on anticoagulation was comparable to the risk of major bleeding (Table 1). Outcomes by stroke and bleeding risk CHA2DS2-VASc: mean 3.1±1.38 HAS-BLED: mean 2.5±1.1 All patients Low risk (0, 1 if female) Intermediate risk (1, 2 if female) High risk (≥2, 3 if female) Low risk (0, 1) Intermediate risk (2, 3) High risk (≥4) Patients, N 233 1,133 6,304 1,224 4,932 1,516 7,672 First occurrence of outcomes, n (%/year) All-cause mortality 2 (0.92%) 12 (1.11%) 242 (4.09%) 14 (1.21%) 161 (3.47%) 82 (5.78%) 257 (3.56%) Intracranial haemorrhage 0 (0.00%) 1 (0.09%) 19 (0.32%) 2 (0.17%) 10 (0.22%) 8 (0.56%) 20 (0.28%) Major bleeding 0 (0.00%) 6 (0.56%) 62 (1.05%) 2 (0.17%) 43 (0.93%) 23 (1.63%) 68 (0.95%) Stroke/SEE 0 (0.00%) 4 (0.37%) 59 (1.00%) 3 (0.26%) 41 (0.89%) 19 (1.34%) 63 (0.88%) SEE, systemic embolic event. Conclusions In this unselected cohort of patients with AF anticoagulated with edoxaban, high CHA2DS2-VASc and HAS-BLED scores were associated with higher risks of stroke, bleeding and death. Indirectly compared with the expected rates in non-anticoagulated patients, our data underpin the value of anticoagulants such as edoxaban in patients at high risk of stroke and bleeding. Acknowledgement/Funding The ETNA-AF Registry was funded by Daiichi Sankyo Europe GmbH, Munich, Germany.

Background Left atrial (LA) strain has a prognostic value for atrial fibrillation (AF) recurrence after AF ablation. The value of LA strain as a predictor of AF recurrence after thoracoscopic AF surgery in patients in sinus rhythm (SR) or AF during echocardiography is unknown. Purpose To assess the association between LA strain and AF recurrence after thoracoscopic surgery for AF in both patients in SR and AF during baseline echocardiography. Methods Patients participating in the AFACT trial (n=240) with baseline transthoracic echocardiography (TTE) suitable for LA strain analysis were included in this subanalyses. All patients underwent thoracoscopic pulmonary vein isolation (PVI) with left atrial appendage (LAA) exclusion, and were randomized to ganglion plexus (GP) or no GP ablation. LA strain and mechanical dispersion (MD) of the LA reservoir, conduit and contraction phase were determined retrospectively from TTE images of both patients in AF and SR before thoracoscopic AF surgery. AF recurrence was defined as any recorded atrial tachyarrhythmia lasting >30 sec during a one year FU period. Results A total of 204 patients (58.6±7.8 years, 73% male, 57% persistent AF) were included. Of the 204 patients 121 (59%) were in SR and 83 (41%) were in AF during baseline TTE. Patients in SR during TTE had higher LA strain values and lower MD compared to patients in AF. Of all patients, those with AF recurrence had lower LA strain of the reservoir phase (13.0% vs. 16.6%; p=0.003) and contraction phase (7.4% vs. 11.5%; p=0.012). MD of the contraction phase was increased in patients with AF recurrence (65.1msec vs. 19.2 msec; p=0.003). Multivariable cox regression analysis showed an association between LA strain, MD and AF recurrence (figure). Conclusions Left atrial strain and mechanical dispersion prior to thoracoscopic AF surgery are associated with recurrence of AF. LA strain showed to be a valuable tool to add in the decision making for thoracoscopic AF surgery regardless rhythm during baseline echocardiography.

Background Many adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). An implantable cardioverter-defibrillator (ICD) may prevent SCD, but the evidence for primary prevention indications is still unsatisfactory. Study Design PREVENTION-ACHD is a prospective study with which we aim to prospectively validate a new risk score model for primary prevention of SCD in ACHD patients, as well as the currently existing guideline recommendations. Patients are screened using a novel risk score to predict SCD as well as current ICD indications according to an international Consensus Statement. Patients are followed up for two years. The primary endpoint is the occurrence of SCD and sustained ventricular arrhythmias. The Study was registered at ClinicalTrials.gov (NCT03957824). Conclusion PREVENTION-ACHD is the first prospective study on SCD in ACHD patients. In the light of a growing and aging population of patients with more severe congenital heart defects, more robust clinical evidence on primary prevention of SCD is urgently needed. Electronic supplementary material The online version of this article (10.1007/s12471-019-1297-3) contains supplementary material, which is available to authorized users.

BACKGROUND AND AIM: Obesity is a recognized risk factor for new-onset atrial fibrillation (AF). The association between body fat distribution, which is measured by body mass index (BMI) and waist-hip ratio (WHR), its changes, and new-onset AF is conflicting. METHODS AND RESULTS: Participants of the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort study were included, with exclusion criteria of prevalent AF, rheumatic heart disease, and cancer. AF was confirmed by the International Classification of Diseases-10 hospital discharge code I48. Adjusted sex-specific Cox proportional hazards models were used to quantify the AF risk per 1 standard deviation increase and for quintiles of adiposity indices. A total of 10,885 men and 12,857 women were followed up for a median of 19 years, yielding 451,098 person-years. New-onset AF was diagnosed in 1408 (12.9%) men and 1102 (8.6%) women. Multivariable analyses showed that BMI predicted new-onset AF in all, while WHR predicted only in men. New-onset AF risk gradually increased across the range of adiposity indices: for men in the highest BMI quintile, HR: 1.59 (CI 1.32-1.91, p for trend

Background: Eight-mm ablation catheters are widely used in cavotricuspid isthmus ablation (CTI) for treatment of right sided atrial flutter. However a high success rate, these large ablation tips comes with adisadvantage of lower resolution of fractionated signals. Purpose:The aim of this study was to evaluate the additional diagnostic value of the electrograms recorded from mini electrodes (MEs) in an 8-mm ablation catheter tip during CTI. Methods: CTI-Ablation procedures were compared retrospectively in two groups, namely, group A: The Abbott Safire 8-mm tip with a 3D mapping system (n =37) and group B: The Boston Scientific MiFi IntellaTip XP 8-mm tip without a 3D mapping system (n=13). We analyzed acute procedural success, ablation characteristics and recurrence rate at one-year follow-up. Electrograms from MEs were analyzed right before the onset of the critical ablation application that resulted in acute CTI-block. We determined whether these ME electrograms had additional diagnostic value in addition to of the 8-mm tip derivedelectrogram. Results: At the onset of the critical ablation application, the MEs had an important additional value in 3 out of 13 cases as local signals were sensed on the MEs that were not recorded by the 8-mm tip electrode. In 2cases the ME did not show local electrograms although the ablation was still effective. Acute procedural and long-Term success were observed in all patients. No differences were found in time to bidirectional block, procedure time or fluoroscopic exposure. Conclusions: Our data show that signals recorded from the MEs had additional diagnostic value, but only in a small percentage of the patients. We did not observe, although omitting 3D-mapping in the ME group, any difference between groups with regard to procedural or ablation characteristics during CTI-Ablation.