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Funding Acknowledgements Type of funding sources: None. Background Recent ESC Atrial Fibrillation guidelines introduced some changes in the options for rate control, such as the possibility to combine beta-blockers (BB) and non-dihydropyridine calcium channel blockers (NDCC), to address the need of personalized pharmacologic rate control strategy for AF. However, there are limited data on this topic. Purpose The aim of our study was to explore the prognostic impact of a personalized therapy (PT) for rate control, including the use of NDDC in patients with heart failure (HF) or in combination with BB, compared to standard rate control therapy (ST) as defined by previous ESC guidelines. Methods This is a single centre prospective observational registry on patients referred to our University Hospital for the management of AF between October 2013 and February 2019. Results We enrolled 1112 patients on exclusive rate control treatment, 125 (11.2%) were identified as patients with PT and 987 (88.8%) were on ST. In the PT group, 93/125 (74.4%) patients were prescribed BB + NDCC (±digoxin), while 85/125 (68.0%) were HF patients prescribed with NDCC, diltiazem in all cases. The mean age of patients was 73.5±12.0 years and 72.5±12.7 years in ST and PT groups, respectively. The two cohorts were homogeneous in terms of male prevalence, left ventricular ejection fraction and CHA2DS2-VASc score; while, HF was more frequent in PT group both in terms of patients with NYHA class ≥2 (41.3% in ST vs. 64.8% in PT, p Conclusions Our results suggest a potential outcome benefit of NDCC for rate-control in AF patients, either alone or in combination with BB, also in selected patients with HF. Future controlled studies are needed to confirm our findings, and to identify subjects with higher benefit from such personalized rate-control strategies.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health. Background At the beginning of the COVID-19 emergency, important restrictions in hospital admissions for non-urgent procedures, to reduce the spread of the epidemic and to direct resources for the management of patients affected by the SARS-COV2 virus were required. Furthermore, in the same period there was a significant reduction of admissions for cardiological emergencies, too. The nationwide impact of COVID-19 pandemic on invasive procedures, such Pacemakers (PM) and Implantable Cardioverter-Defibrillators (ICD) interventions, is unknown. Purpose To evaluate the trend of PM and ICD procedures performed in Italy in the last 10 years and particularly in the pandemic period. Methods All the Italian Hospital Discharge Records (Schede di Dimissione Ospedaliera – SDO) from 2012 to 2021, sent by the Italian Ministry of Health to the National Institute of Health (NIH, Istituto Superiore di Sanità-ISS) were reviewed. Among these, only records including ICD or PM procedures, either primary or secondary, and correctly reporting patient’s age and gender, were selected. The ICD9-CM codes, single and combined, relating to PM and ICD procedures were selected a taxonomy arranged into 16 groups of procedures was defined. PM procedures were also divided in 1°implant and replacement, while ICD could be considered as total procedures only. Results From 2012 to 2019 the yearly number of total PM procedures was quite stable, ranging from 63.498 (1.069/million inhabitants) to 68.807 (1.150/million). In 2020, a reduction of total procedures (38.411, 1078/million, -11% towards 2019) and 1st implant of PM (from 52.216 to 43.962, -16%), but not PM replacement, (from 16.591 to 17.331, +4%) was observed; at beginning of pandemic period (April 2020), the drop in total PM procedures in comparison to the 2018 and 2019 average value was 49%. In 2021, an increase to values exceeding the pre-pandemic numbers, was observed (total procedures 69.330, 1170/million, 49.555 1° implants, 19.775 replacements). For ICD, a slow increase of the procedure rate was observed from 2012 (20.774, 350/million) to 2017, 24.255, 400/million); afterwards, a small reduction of implants was observed in 2018 (22.616, 378/million) and 2020 (22.355, 375/million). The drop in ICD procedures observed in April 2020, compared to the 2018 and 2019 average value, was 46%. In 2021 the rate of ICD procedures (25.384, 429/million) increased more than to the pre-pandemic values. No significant changes in PM and ICD indications were observed during the study interval. Conclusions During the first year of COVID-19 pandemic, a reduction of PM and ICD procedures was observed, especially in the first period (April 2020); for PM, no reduction of replacements was observed in 2020, while the reduction of 1° PM implant and ICD procedures was compensated by an increase of activity in 2021.

Funding Acknowledgements Type of funding sources: None. Introduction Remote monitoring (RM) technologies have the potential to improve patient care by increasing compliance, providing early indications of heart failure (HF) decompensation, and potentially allowing for optimization of therapy to prevent HF admissions. The aim of this observational, retrospective study was to assess the clinical and economic consequences of RM vs standard monitoring (SM) through in-office cardiology visits, in patients carrying an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRTD). Methods Clinical and resource consumption data of this retrospective analysis were extracted from the Electrophysiology Registry of our Cardiology Unit, which has been systemically collecting patient information from January 2011 to February 2022. From a clinical standpoint, survival analysis was conducted, and incidence of CV-related hospitalizations was measured. From an economic standpoint, direct costs of RM and SM patients were collected to compare the cost per treated patient over a 2-year time horizon. Propensity score matching (PSM) was used to reduce the effect of confounding biases and the unbalance of patient characteristics at baseline. Results In the enrollment period, N=402 patients carrying ICD/CRTD met the inclusion criteria and were included in the analysis (N=189 patients -47.0%- followed through SM; N=213 patients -53.0%- followed through RM). After PSM, comparison was limited to N=191 patients in each arm (Figure 1). After a follow-up of 2 years since ICD/CRTD implantation, mortality rate for any cause was 1.6% in the RM group and 19.9% in the SM group (log-rank test, p Conclusion RM of patients carrying ICD/CRTD improves short-term (2-year) morbidity and mortality risks, compared to SM (based on the traditional in-office visit approach) and finally reduces direct management costs for both hospitals and healthcare services

Funding Acknowledgements Type of funding sources: None. Aims Patients with atrial fibrillation (AF) frequently experience sleep disorder breathing, and both conditions are highly prevalent in presence of heart failure (HF). We explored the association between sleep apnea (SA) and the HF status and the incidence of AF in patients with implantable defibrillators (ICD). Methods Data were prospectively collected from 411 consecutive HF patients with ICD. The HF status was measured by the multisensor HeartLogic Index, and the ICD-measured Respiratory Disturbance Index (RDI) was computed to identify severe SA. The endpoints were: daily AF burden of ≥5minutes, ≥6hours and ≥23hours. Results During a median follow-up of 26 months, the time IN-alert HF state was 13% of the total observation period, according to the HeartLogic algorithm (Index >16). The RDI value was ≥30 episodes/h (severe SA) during 58% of the observation period. An AF burden of ≥5 minutes/day was documented in 139 (34%) patients, ≥6 hours/day in 89 (22%) patients, and ≥23 hours/day in 68 (17%) patients. The IN-alert HF state was independently associated with AF regardless of the daily burden threshold: hazard ratios from 2.17 for ≥5 min/day to 3.43 for ≥23 h/day (p Conclusions In patients with heart failure (HF) and implantable defibrillators (ICD), the occurrence of atrial fibrillation (AF) was independently associated with the worsened HF status measured by a multisensor ICD algorithm and with ICD-diagnosed severe sleep apnea (SA). The HF status was independently associated with AF regardless of the daily burden, while severe SA was mainly associated with shorter AF episodes. The coexistence of these two conditions occurs rarely but is associated with a very high rate of AF occurrence.

Funding Acknowledgements Type of funding sources: None. Background Predicting worsening heart failure (WHF) events in chronic heart failure (HF) patients is important to avoid hospitalizations. In patients implanted with cardiac implantable electronic devices (CIEDs) remote monitoring may help to identify patients at risk of WHF thanks to the ability to monitor physiological parameters that may change before WHF. However, clinicians need to know patient HF-related signs, symptoms and therapy non-compliance to determine type and time of necessary interventions. A patient Smartphone Application (App) may be an ideal option to remotely collect this information from patients and help clinicians in the decision-making process. Purpose to assess the penetration of App technology in a large real-world HF population and to evaluate patient willingness and compliance to use a HF-dedicated App to weekly send a diary on HF signs, symptoms and therapy compliance to the cardiologist. Methods From January 2021 to July 2022, 10 Italian hospitals in the framework of the One Hospital ClinicalService project designed a questionnaire on the use of App technology and submitted it to their HF patients with CIED during scheduled in-hospital follow-up. If the patient or his caregiver was able and willing to use Apps, the HF-dedicated App was activated on his smartphone. Compliance in using the App (= percentage of weeks in a year with at list an App diary received by all patients) was evaluated for patients who have received it for at least one year. Results 495 HF patients with CIED (age 67±13 years, 79% males, 26% NYHA III-IV, LVEF 35±11%, 60% with 3-chamber CIED, 43% with high school qualification) completed the questionnaire. Out of them, 80% have access to App technology, directly or through a caregiver; ≥62% can do all high-level activities (APP installation, email, web browsing) and 21% has already used Health Apps; 73% is willing to weekly send a diary using the App. 311 patients (63% of respondents) downloaded the HF-dedicated App on their or caregiver’s smartphone. They were younger and with higher school qualification than those not receiving the App. No other difference in baseline characteristics was seen. 138 patients have received the App for at least 1 year. Their compliance decreased during time, from 60% (weeks 1-13) to 42% (weeks 40-52; p Conclusion In a large real-world HF population with CIED patients, the penetration of Smartphone technology was high and > 60-year-old patients had higher compliance to the use of a new HF-dedicated App compared to younger patients. The use of Smartphone App technology to collect WHF sign/symptoms is feasible and may improve remote management of HF patients.

Funding Acknowledgements Type of funding sources: None. Background The COVID-19 pandemic has highlighted the role of telemedicine in reducing face-to-face visits. Telemedicine requires either the use of digital support methods and a minimum technological knowledge of the patients. Digital health literacy, defined as the use of digital literacy skills to find and use health information and services, may influence the use of telemedicine in most patients, particularly in specific groups such as those with frailty. Aim To explore the association between frailty status, patients' use of digital tools and digital health literacy to determine whether it would be possible to implement control visits in patients followed in a cardiac arrhythmias outpatient clinic. Methods We prospectively enrolled consecutive patients referring to arrhythmias outpatient clinics of our department from March to September 2022. Patients were divided according to frailty status as defined by the Edmonton Frail Scale (EFS) into three subgroups: robust, pre-frail, and frail. The degree of health digital literacy was assessed through the Digital Health Literacy Instrument (DHLI) Scale. The DHLI explores 7 digital skill categories measured by 21 self-report questions. The self-report questions require participants to rate on a 4-point scale how difficult different tasks are and how frequently they encounter certain difficulties on the Internet. The total DHLI and each skill category score were calculated by summing the received scores in every single domain (3 questions per each skill category) and reported as mean and median. A multivariable logistic regression analysis was also use to evaluate the association between the non-use of the Internet and frailty status. Results A total of 300 patients were enrolled (36.3% females, median age 75 [66-84]) and stratified according to frailty status as: (i) Robust (EFS ≤ 5; n = 212, 70.7%), (ii) Pre-Frail (EFS 6-7; n = 47, 15.7%), and (iii) Frail (EFS ≥ 8; n = 41, 13.7%). Frail patients used less frequently smartphones, PC and emails and had less availability of Wi-Fi at home compared to robust patients (Table 1). At the multivariable logistic regression analysis, frailty was significantly associated with the non-use of the Internet (adjusted odds ratio, 2.58 95% confidence interval 1.92-5.61). Digital health literacy score decreased as the level of frailty increased in all the domains explored (operational skills, navigation skills, information searching, evaluating the reliability of the information, determining the relevance of online information, adding self-generated content and protecting privacy while using the internet, all p Conclusions Frail patients are characterized by a lower use of digital tools and access to the Internet even though these patients would benefit the most from telemedicine. Digital skills are strongly influenced by frail status highlighting the need to implement digital health literacy with specific interventions in this population.

Funding Acknowledgements Type of funding sources: None. Background The incidence of death and infections in patients implanted with cardiac implantable electronic devices (CIEDs) are not fully known yet (1,2). Purpose To describe the incidence of death and device’s infection and its potential predictors in a contemporary cohort of CIED patients. Methods All consecutive patients implanted with a CIED at our tertiary institution were prospectively enrolled. Follow-up was performed every six months and clinical events recorded by expert electrophysiologists. For the purpose of the present analysis, we considered patients with a potential follow-up of at least 24 months. Results Between 01/09/2018 and 01/09/2020, a total of 838 patients were enrolled (34.6% female; age 77 [70-84]; PADIT score 2 [2-4]). Pacemaker (PM) and implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy and defibrillator (CRT-D) were implanted in 569 (68%) and 269 (32%) patients respectively. All patients had pre-implant antibiotic prophylaxis and 5.5% had an antibiotic-eluting envelope. Follow-up data were available for 832 (99.2%) patients. After a median follow-up of 42.3 (30.2-56.4) months, 212 (25.5%) patients died and 5 (0.6%) had a CIED infection. Four out of five patients required CIED extraction, while 1 patient antibiotics only. At multivariate Cox-regression analysis, age (hazard ratio [HR] 1.08; 95% confidence interval [CI] 1.05-1.10) and dialysis (HR 6.18; 95%CI 3.40-11.25) were independently associated with death, while first implant was associated with a lower risk as compared to subsequent procedures (HR 0.63; 95%CI 0.46-0.85) (Figure 1). Conclusions In large contemporary cohort of CIED patients, mortality was substantially high and associated with clinical factors depicting a population at risk. On the other hand, the incidence of CIED infections was low.

Funding Acknowledgements Type of funding sources: None. Background Infections of Cardiac implantable electronic device (CIED) are rare but serious complications impacting patients and the whole heath care system. Recently, a significative reduction in major CIED infections within 12 months of the procedure has been showed by the use of an absorbable antibiotic-eluting envelope. The aim of the analysis is to evaluate the impact of the use of the envelope on infection-related clinical events (including pocket hematoma, infection, and systemic infection) reduction in a real word patient population Methods Data on patients underwent CIED implantation or replacement were collected prospectively in the framework of One HospitalClinicalService project. Patients were divided into two groups according to the utilization of an absorbable antibiotic-eluting envelope or the non-usage of the envelope. Results Out of 1819 patients, 872 (47.9%) were implanted with an absorbable antibiotic-eluting envelope and denoted as the Envelope group. Accordingly, 947 (52.1%) patients were categorized as the control group. As compared to control, patients with envelope had higher thrombo-embolic risk, higher BMI, lower LV ejection fraction and in general had more comorbidities. During a mean follow-up of 1.4 year, the incidence rate per 100 patients-months of infective related events were significantly greater in the control compared to the Envelope group (2.85% vs 1.26%, p< 0.001). The 48-month cumulative incidence of infective related events was 6.7% in the control and 2.9% in the Envelope group (HR:0.47; 95%CI: 0.27-0.95, p= 0.032). Fig1 When considering a subgroup of 1170 patients matched by PADIT score, the incidence of infective related events was 1.0 % (6/585) in the envelope and 3.8% (22/585) in the envelope and control group, respectively, p=0.002. Conclusions In our analysis, the use of envelope in the general CIED population was effective to reduce the risk of systemic or pocket infection, or pocket hematoma

Introduction There is increasing concern regarding the burden of clinical complexity, beyond thromboembolic risk, in patients with atrial fibrillation (AF). Also, clinical complexity is heterogenous and entails differential impact on the patients' clinical course. Purpose To explore different complexity features in AF patients in determining differences in clinical management and outcomes. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Features of complexity were analysed in the context of the following high-risk groups: i) only CHA2DS2-VASc ≥2; ii) history of stroke/bleeding; iii) chronic kidney disease (creatinine clearance Results A total of 10285 patients (mean [SD] age 68.8 [11.5] years, 4107 [39.9%] females) were included in the analysis. Of these, 3944 (38.3%) had only CHA2DS2-VASc ≥2; 412 (4.0%); history of stroke/bleeding; 1480 (14.4%) CKD; 1007 (9.8%) were frail; 1315 (12.8%) had ≥2 criteria; and 2127 (20.7%) were low-risk. After adjustment for age, sex, type of AF and EHRA score, compared to low-risk patients, all the other groups were associated with OAC prescription but with progressively lower odds ratio, while those ≥2 criteria which were least likely prescribed with OAC (Table 1). After a mean (SD) 634.5 (223.0) days of follow-up, a total of 1432 events were recorded. After adjustment for confounders, Cox regression analysis found that all the complexity groups were associated with a higher risk of the composite outcome across the groups (Figure 1). In patients with available data about ABC (Atrial fibrillation Better Care) pathway adherence, the latter adherence was associated a significant incidence rate reduction (IRR) compared to non-ABC adherence in those with ≥2 criteria of clinical complexity (IRR 0.46, 95% CI 0.30–0.71), and in the CKD complexity group (IRR 0.57, 95% CI 0.41–0.81). Conclusions In a large contemporary cohort of European AF patients, features of clinical complexity affect differently prescriptions of OAC. All the subgroups of clinical complexity were associated with a higher risk of adverse outcomes, which were reduced by adherence to ABC pathway. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and PfizerAlliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022).

Background The association between sleep apnea (SA) and atrial fibrillation (AF) has been well described. However, it remains unclear whether the association is causative or primarily dependent on shared comorbidities such as obesity. The Respiratory Disturbance Index (RDI) computed by an implantable cardioverter defibrillator (ICD) algorithm accurately identifies severe SA, whether central or obstructive in origin. Purpose In the present analysis we studied in patients with heart failure the contribution of obesity in the relationship between SA, measured by RDI, and AF. Methods Patients with ejection fraction ≤35% implanted with an ICD endowed with an algorithm (ApneaScan) that calculates the RDI each night, were enrolled and followed-up for 24 months. The weekly mean RDI value was considered, as calculated during the entire follow-up period. The endpoint was daily AF burden of ≥6 hours. Results 164 patients (age 67±10 years, 75% male, ejection fraction 29±5%) had usable RDI values during the entire follow-up period. Body mass index (BMI) was Conclusions In heart failure patients, we confirmed the association between ICD-detected SA and AF, an association that persisted independent of patient body habitus. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The study is supported by a research grant from Boston Scientific

Introduction Few data exist on the impact of thromboembolic risk dynamics in determining a higher risk of adverse clinical outcomes in atrial fibrillation (AF) patients. Moreover, no evidence is available about the possible impact of integrated care, as defined by the `Atrial fibrillation Better Care' (ABC) pathway, in modulating the clinical outcomes associated with the dynamic changes in risk. Purpose To study thromboembolic risk dynamics and the relationship with integrated care, also in determining the risk of adverse outcomes in AF patients. Methods We analysed patients from the randomized controlled SPORTIF III and V trials. Thromboembolic risk was assessed according to CHA2DS2-VASc score. Integrated care was assessed according to ABC pathway adherence. The primary endpoint was the composite clinical outcome of all-cause death and major adverse cardiovascular events. Results A total of 3589 patients [mean (SD) age was 70.9 (8.8) years; 30.4% female; median [IQR] baseline CHA2DS2-VASc 3 [2–4]) were available for the analysis. Over a mean 573.8 (SD 129.5) days of follow-up, a total of 67 (1.9%) reported an increase in CHA2DS2-VASc score, with a mean (SD) delta of 0.0295 (0.2257). Among those with increasing CHA2DS2-VASc, 29 (43.3%) reported a 1-point increase, 37 (55.2%) reported a 2-point increase and only 1 (1.5%) reported a 3-point increase. A total of 948 (26.4%) patients were managed adherent to ABC pathway and overall, a median (IQR) of 2 [1–3] ABC criteria were fulfilled in the patients included. An adjusted linear regression analysis found that an increasing number of ABC pathway criteria fulfilled was inversely associated with increase in CHA2DS2-VASc score throughout follow-up (Beta −0.010, 95% CI −0.019 to −0.001), p=0.045), while considering the single ABC criteria, only the “C” criteria was inversely associated with an increase in CHA2DS2-VASc score (Beta −0.018, 95% CI −0.034 to −0.001, p=0.038). A total of 255 (7.1%) clinical events were recorded. An adjusted Cox regression analysis found that both increasing CHA2DS2-VASc score (HR 2.67, 95% CI 2.12–3.36, p Conclusions Integrated care was associated with a lower progression in the thromboembolic risk of AF patients, particular through the optimal management of cardiovascular risk factors and comorbidities. Both increasing thromboembolic risk and increasing adherence to ABC pathway were independently associated, although inversely, with occurrence of adverse clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Background Anaemia is an independent predictor of atrial fibrillation (AF) and a common comorbidity. Real world data on the impact of anaemia on clinical outcomes, and on the benefits and risks of oral anticoagulation (OAC) are limited. Purpose To investigate the association of different degrees of anaemia with adverse outcomes in a cohort of European patients with AF. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry with baseline hemoglobin (Hb) values. Patients were stratified according to World Health Organization (WHO) definition of anaemia: (i) No anaemia (Hb≥12.0g/dl for women and Hb≥13.0g/dl for men), Mild anaemia (Hb 11.0–11.9g/dl for women and Hb 11.0–12.9g/dl for men), and moderate-severe anaemia (Hb ≤10.9 g/dl for both sexes). Primary outcomes were all-cause death, major adverse cardiac events (MACE, as the composite of any thromboembolism (TE)/acute coronary syndrome/cardiovascular death) and major bleeding. Results From the original 11,096 AF patients enrolled in the Registry, 7767 (69.9%) were included in the present analysis (median age 70 years, interquartile range [IQR] 62–77, males 58.3%, CHA2DS2VASc score median 3 [2–4], HAS-BLED median 2 [1–2]). A total of 5973 (76.9%) patients did not have anaemia, 1156 (14.9%) had mild anaemia, and 638 (8.2%) had moderate/severe anaemia. Patients with anaemia were more likely to have more comorbidities, frailty, permanent AF and polypharmacy (≥5 drugs). Overall, 318 (18.4%) patients with anaemia and an indication for anticoagulation [i.e. CHA2DS2-VASc≥1 (males), or ≥2 (females)] did not receive any OAC. After a median (IQR) follow-up of 730 (692–749) days, all-cause death was 10.5% and there were 841 (11.6%) MACE and 186 (2.5%) major bleeds. Kaplan–Meier analysis showed a higher cumulative risk for patients with moderate-severe anaemia for all the outcomes considered (Figure) (Log Rank tests, all p Conclusions In a large contemporary cohort of European AF patients, almost 25% have concomitant anaemia which is associated with an increased risk for all-cause mortality, MACE and major bleeding. Use of OAC was associated with a lower risk of all-cause mortality in patients with moderate-severe anaemia, without significant increased risk of major bleeding. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022)

Background Heart failure (HF) has an intimate bidirectional association with atrial fibrillation (AF). Few data are available about the impact of HF phenotypes (HF with preserved ejection fraction, HFpEF; HF with mildly reduced ejection fraction, HFmrEF; HF with reduced ejection fraction, HFrEF) as predictors for adverse outcomes in AF patients. Purpose To investigate the association of HFpEF, HFmrEF and HFrEF with adverse outcomes in a large contemporary cohort of European AF patients and evaluate the effect of EF throughout its entire spectrum. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. HF patients were categorized according the three phenotypes and compared to those without HF (“non HF”). Main outcome was a composite outcome of all-cause death and major adverse cardiac events (MACE). Results Among the original 11,096 AF patients enrolled, 9857 (88.8%) were included in this analysis (median age 71 years, interquartile range [IQR 63–77], 40.1% females) with median EF 55% [IQR 45–61%] and CHA2DS2-VASc 3 [2–4]). In this cohort, 5935 (60.2%) were non HF patients, and 3240 (32.9%) had HF patients (with HF status and EF values data available). Accordingly, 1662 (51.2%) were categorized as HFpEF; 523 (14.1%) were HFmrEF; and 1235 (35.1%) were HFrEF. After a median follow-up of 731 days [IQR 690–748], the composite outcome was significantly higher throughout HF categories (HFpEF 19.0%, HFmrEF 21.8% and HFrEF 29.6%, compared to non HF 10.7%; p Conclusions Over a two-years follow-up, in a large contemporary cohort of European AF patients, HF phenotypes were associated with a progressively higher risk for adverse outcomes. Lower EF values increased the risk of adverse outcomes both in HF patients and overall AF patients, irrespective of HF phenotype status. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022).

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The “Atrial fibrillation Better Care” (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We analyzed the impact of the ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analyzed clinically complex AF patients, defined as the presence of frailty (according to a 40-items Frailty Index), multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on the risk of all-cause death, major adverse cardiovascular events (MACEs) and the composite outcome of all-cause death and MACE was analyzed through Cox-regression analyses, and delay of event (DoE) analyses; number needed to treat (NNT) was also estimated at 1 year of follow-up. Results Among 9,966 AF patients, 8,289 (92.3%) were clinically complex. Risk of all outcomes was higher among clinically complex patient. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.71, 95% CI 0.57–0.89), major adverse cardiovascular events (MACEs, aHR: 0.68, 95% CI 0.53–0.87) and composite outcome (aHR: 0.69, 95% CI: 0.57–0.84). Using cluster analysis, we identified a high clinical complexity group of AF patients. Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.73, 95% CI 0.55–0.96) and composite outcome (aHR: 0.69, 95% CI 0.57–0.84) in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all-cause death (Figure 1), MACEs, and composite outcome in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the NNTs for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes amongst clinically complex AF patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, several companies have supported the programme with unrestricted grants.

Background The impact of Atrial Fibrillation Better Care (ABC) pathway adherence among high-risk subgroups of patients with atrial fibrillation (AF), ie. those with chronic kidney disease (CKD), advanced age and/or prior thromboembolism remains unknown. We evaluated the impact of ABC pathway adherence on clinical outcomes in these high-risk AF patients. Methods The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. High-risk patients were defined as those with either CKD (eGFR Results A total of 6646 patients with AF were included (median age was 70 [IQR 61–77] years; 40.2% females). There were 3304 (54.2%) `high risk' patients with either CKD (n=1750), older age (n=2236) or prior thromboembolism (n=728). Among these there were 924 (28.0%) managed as adherent to ABC. At 2-year follow-up, a total of 966 (14.5%) patients reported the primary outcome. The incidence of the primary outcome was significantly lower in high-risk patients managed as adherent to ABC pathway (IRR 0.53 [95% CI, 0.43–0.64]). Consistent results were obtained in the individual subgroups [Table]. Using multivariable Cox proportional hazards analysis, ABC adherence in the high-risk cohort was independently associated with a lower risk of primary outcome (aHR 0.64 [95% CI, 0.51–0.80]), as well as in the CKD (aHR 0.51 [95% CI, 0.37–0.70]) and elderly subgroups (aHR 0.69 [95% CI, 0.53–0.90]). Overall, there was greater reduction in the risk of primary outcome as more ABC criteria were fulfilled, both in the overall high-risk patients, as well as in the individual subgroups [Figure]. Conclusion In a large, contemporary European AF cohort there was a significant proportion of high-risk patients. Among these, a low prevalence of integrated care, as assessed by adherence to ABC pathway, was found. Nonetheless, a clinical management adherent to the ABC pathway was associated with a significant reduction in the risk of adverse outcomes, the benefits of which were more significant with increasing number of ABC criteria adherent. Funding Acknowledgement Type of funding sources: None.

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.

BACKGROUND: Implementation of the Atrial fibrillation Better Care (ABC) pathway is recommended by guidelines on atrial fibrillation (AF), but the impact of adherence to ABC pathway in patients with cancer is unknown.OBJECTIVES: To investigate the adherence to ABC pathway and its impact on adverse outcomes in AF patients with cancer.METHODS: Patients enrolled in the EORP-AF General Long-Term Registry were analyzed according to (i) No Cancer; and (ii) Prior or active cancer and stratified in relation to adherence to the ABC pathway. The composite Net Clinical Outcome (NCO) of all-cause death, major adverse cardiovascular events and major bleeding was the primary endpoint.RESULTS: Among 6550 patients (median age 69 years, females 40.1%), 6005 (91.7%) had no cancer, while 545 (8.3%) had a diagnosis of active or prior cancer at baseline, with the proportions of full adherence to ABC pathway of 30.6% and 25.7%, respectively. Adherence to the ABC pathway was associated with a significantly lower occurrence of the primary outcome vs. non-adherence, both in 'no cancer' and 'cancer' patients [adjusted Hazard Ratio (aHR) 0.78, 95% confidence interval (CI): 0.66-0.92 and aHR 0.59, 95% CI 0.37-0.96, respectively]. Adherence to a higher number of ABC criteria was associated with a lower risk of the primary outcome, being lowest when 3 ABC criteria were fulfilled (no cancer: aHR 0.54, 95%CI: 0.36-0.81; with cancer: aHR 0.32, 95% CI 0.13-0.78).CONCLUSION: In AF patients with cancer enrolled in the EORP-AF General Long-Term Registry, adherence to ABC pathway was sub-optimal. Full adherence to ABC-pathway was associated with a lower risk of adverse events.

Funding Acknowledgements Type of funding sources: None. Background Sleep-disordered breathing is highly prevalent in heart failure (HF) and it has been suggested as a risk factor for malignant ventricular arrhythmias. The Respiratory Disturbance Index (RDI) algorithm computed by select implantable cardioverter defibrillators (ICDs) can identify severe sleep apnea (SA). Purpose In the present analysis we evaluated the association between ICD-detected SA and the incidence of appropriate ICD therapy in patients with HF. Methods We enrolled 411 HF patients (age 69±10years, 77% male, ejection fraction 32±8%), implanted with an ICD endowed with an algorithm (ApneaScan, Boston Scientific) that calculates the RDI each night. In this analysis the weekly mean RDI value was considered. The endpoint was the first appropriate ICD shock. The median follow-up was 26 months [25th–75th percentile: 16-35]. Results During follow-up, one or more ICD shocks were documented in 58 (14%) patients. Patients with shocks were younger (66±13years versus 70±10years, p=0.038), and more frequently implanted for secondary prevention (21% versus 10%, p=0.026). The maximum RDI value calculated during the entire follow-up period did not differ between patients with and without shocks (55±15episodes/h versus 54±14episodes/h, p=0.539). However, the ICD-detected RDI showed a considerable variability during follow-up. The overall median of the weekly RDI was 33episodes/h [25th–75th percentile: 24-45]. Using a time-dependent Cox regression model, the continuously measured weekly mean RDI≥45episodes/h was independently associated with shock occurrence (HR:4.63, 95%CI:2.54-8.43, p Conclusions In HF patients, patients were more likely to receive appropriate ICD shocks during periods of time when they exhibited more sleep-disordered breathing.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

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 Management of patients with atrial fibrillation (AF) and malignancy is a clinical challenge given the paucity of evidence supporting the appropriate clinical management. Purpose To evaluate the outcomes of patients with active or prior malignancy in a large contemporary cohort of European AF patients. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. We stratified the population into three categories (i) No Malignancy (NoM) (ii) Prior Malignancy (PriorM) and (iii) Active Malignancy (ActM). The primary outcome for this analysis was all-cause death among the three groups. The association between anticoagulant treatment, all-cause death and haemorrhagic events was also evaluated. Results Among the original 11 096 AF patients enrolled, 10 383 were included in this analysis (median age 71 years (interquartile range [IQR] 63–77, males 59.7%). Of these, 9 597 (92.4%) were NoM patients, 577 (5.6%) PriorM and 209 (2%) ActM. Patients with malignancy (prior or active) had a higher median age, median CHA2DS2-VASc and HAS-BLED scores, compared to patients without malignancy (p After a median follow-up of 730 days [IQR 692–749], 982 (9.5%) patients died. Among all deaths, the proportion of cardiovascular death was different according to the three groups (40.0% in NoM, 26.0% in PrioM and 22.2% in ActM, p=0.002). For all cause-death, Kaplan-Meier analysis showed a progressively higher cumulative risk in the PriorM and ActM groups compared to NoM patients (Figure 1). On multivariable Cox regression analysis, adjusted for CHA2DS2-VASc score, use of AC, type of AF and chronic kidney disease, ActM group was independently associated with a higher risk for all cause death (hazard ratio [HR] 2.90, 95% confidence interval [CI] 2.23–3.76) while PriorM group was not. Among PriorM and NoM patients, multivariable adjusted Cox regression analysis found that the use of any AC was independently associated with a lower risk for all-cause death (HR 0.36, 95% CI 0.19–0.66; HR 0.66, 95% CI 0.54–0.81). No significant association between AC and all-cause death was found for ActM patients. Conclusions In a large contemporary cohort of European AF patients, active malignancy was found to be independently associated with all-cause death. Use of any AC was associated with a lower risk for all-cause death in patients with no malignancies and with prior malignancies, but with no significant association amongst patients with active malignancies. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022). Figure 1. Kaplan-Meier for all-cause death

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.

Background Frailty is a clinical syndrome characterized by a reduced physiologic function, increased vulnerability to stressors, and an increased risk of adverse outcomes. Patients with Atrial Fibrillation (AF) are often burdened with a high number of comorbidities and prone to frailty. The prevalence of frailty, its management and association with major outcomes in patients with AF are still unclear. Purpose To estimate the pooled prevalence of frailty in patients with AF, as well as its association with AF-related risk factors and comorbidities, oral anticoagulants (OAC) prescription, and major outcomes. Methods We systematically searched PubMed and EMBASE, from inception to 31st January 2021, for studies reporting the prevalence of frailty (irrespective of the tool used for assessment). Pooled prevalence, odds ratio (OR), and 95% Confidence Intervals (CI) were computed using random-effect models; heterogeneity was assessed through the inconsistency index (I2). This study was registered in PROSPERO: CRD42021235854. Results A total of 1,116 studies were retrieved from the literature search, and 31 were finally included in the systematic review (n=842,521 patients). The frailty pooled prevalence was 39.6% (95% CI=29.2%-51.0%, I2=100%; Figure 1). Significant subgroup differences were observed according to geographical location (higher prevalence found in European-based cohorts; p=0.003) and type of tool used for the assessment (higher prevalence in studies using the Clinical Frailty Scale and Tilburg Frailty Index tools; p Conclusions In this systematic review and meta-analysis analysis, the prevalence of frailty was high in patients with AF, and associated with study-level mean age and prevalence of several stroke risk factors. Frailty may influence the management of patients, and worsening the prognosis for all major AF-related outcomes. Funding Acknowledgement Type of funding sources: None. Prevalence of Frailty among AF patients

Introduction Sleep apnea (SA), as measured by polysomnography, is a risk factor for atrial fibrillation (AF). The DASAP-HF study previously demonstrated that the Respiratory Disturbance Index (RDI) computed by an implantable cardioverter defibrillator (ICD) algorithm accurately identifies severe SA, is associated with cardiovascular events, and independently predicts death. Purpose In the present analysis we tested the hypothesis that device-detected RDI could also predict AF burden. Methods Patients with left ventricular ejection fraction ≤35% implanted with an ICD were enrolled and followed-up for 24 months. One month after implantation, patients underwent a polysomnographic study. The weekly average RDI value was considered, as calculated by the algorithm during the entire follow-up period and over a 1 week period preceding the sleep study, and patients were stratified according to an RDI value ≥ or Results 164 enrolled patients had usable RDI values during the entire follow-up period. Severe SA (RDI≥30 episodes/h) was diagnosed in 92 (56%) patients at the time of the polysomnographic study. During a median follow-up of 25 months, AF burden ≥5 minutes/day was documented in 70 (43%), ≥6 hours/day in 48 (29%), and ≥23 hours/day in 33 (20%) patients. Device-detected RDI≥30 episodes/h at the time of the polysomnographic study, as well as the polysomnography-measured apnea hypopnea index ≥30 episodes/h, were not associated with the occurrence of the endpoints, using a Cox regression model. However, using time-dependent Cox model continuously measured weekly average RDI≥30episodes/h was independently associated with AF burden ≥5 minutes/day (HR: 2.13, 95% CI: 1.24–3.65, p=0.006), ≥6 hours/day (HR: 2.75, 95% CI: 1.37–5.49, p=0.004), and ≥23 hours/day (HR: 2.26, 95% CI: 1.05–4.86, p=0.037), after correction for history of AF, left atrial diameter, and gender. Conclusions In heart failure patients implanted with an ICD, device-diagnosed severe SA is associated with a higher risk of AF. In particular, severe SA on follow-up data review identifies patients who are from two- to three-fold more likely to experience an AF episode, according to various thresholds of daily AF burden. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Promoted by the Italian Heart Rhythm Society (AIAC).Supported by a research grant from Boston Scientific.

Background Atrial fibrillation (AF) screening has the potential to increase early detection and possibly reduce complications of AF. Guidelines recommend screening, but the most appropriate approaches are unknown. Purpose We aimed to explore the views of stakeholders across Europe about the opportunities and challenges of implementing four different AF screening scenarios. Method This qualitative study included 21 semi-structured interviews with healthcare professionals and regulators potentially involved in AF screening implementation in nine European countries. Data were analysed using thematic analysis. Results Three themes evolved. 1) Current approaches to screening: there are no national AF screening programmes, with most AF detected in symptomatic patients. Patient-led screening exists via personal devices, creating screening inequity by the reach of screening programmes being limited to those who access healthcare services. 2) Feasibility of screening approaches: single time point opportunistic screening in primary care using single lead ECG devices was considered the most feasible approach and AF screening may be possible in previously unexplored settings such as dentists and podiatrists. Software algorithms may aid identification of patients suitable for screening and telehealth services have the potential to support diagnosis. However, there is a need for advocacy to encourage the use of telehealth to aid AF diagnosis, and training for screening familiarisation and troubleshooting. 3) Implementation requirements: sufficient evidence of benefit is required. National rather than pan-European screening processes must be developed due to different payment mechanisms and health service regulations. There is concern that the rapid spread of wearable devices for heart rate monitoring may increase workload due to false positives in low risk populations for AF. Data security and inclusivity for those without access to primary care or personal devices must be addressed. Conclusions There is an overall awareness of AF screening. Opportunistic screening appears to be most feasible across Europe. Challenges that need to be addressed concern health inequalities, identification of best target groups for screening, streamlined processes, the need for evidence of benefit, and a tailored approach adapted to national realities. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): H2020 Screening ScenariosGraphical abstract

Background During the COVID-19 pandemic, implementation of telemedicine has represented a new potential option for outpatient care. Purpose The aim of our study was to evaluate digital literacy among cardiology outpatients. Methods From March to June 2020 a survey on telehealth among cardiology outpatients was performed. Digital literacy was investigated through six main domains: age; sex; educational level; Internet access; availability of Internet sources; knowledge and use of teleconference software programs. Results The study included 1067 patients, median age 79 years, 41.3% females. The majority of the patients (58.0%) had a secondary school degree, but among patients aged ≥75 years old the most represented educational level was primary school or none. Overall, for Internet access, there was a splitting between “never” (42.1%) and “every day” (41.0%), while only 2.7% answered “at least 1/month” and 14.2% “at least 1/week”. In the total population, the most used devices for Internet access were smartphones (59.0%), and WhatsApp represented the most used app (57.3%). Internet users were younger compared to non-Internet users (63 versus 78 years old, respectively) and with a higher educational level. Age and educational level were associated with non-use of Internet (age-per 10-year increase odds ratio [OR] 3.07, 95% confidence interval [CI] 2.54–3.71, secondary school OR 0.18, 95% CI 0.12–0.26, university OR 0.05, 95% CI 0.02–0.10) (Figure 1). Conclusions Telemedicine represents an appealing option to implement medical practice, and for its development it is important to address the gaps in patients' digital skills, with age and educational level being key factors in this setting. Funding Acknowledgement Type of funding sources: None. Figure 1. Factors associated with Internet non-use

Background Sub-clinical atrial fibrillation (SCAF) and atrial high-rate episodes (AHREs), seen as high-frequency atrial tachyarrhythmias in patients with cardiac implantable electronic devices (CIEDs), have gained prominence as determinants of clinical atrial fibrillation (AF) and increased stroke risk. As a result, several studies investigating their role in predicting the onset of AF and AHRE-related outcomes have been conducted but uncertainty exists on the epidemiology of AHRE. Purpose To estimate the incidence of SCAF, according to presence of AHREs in patients with CIEDs, through a systematic review and meta-analysis of the available literature. Methods PubMed and EMBASE were searched from inception to 27th January 2021 for all studies documenting the incidence of AHREs in patients with CIEDs. We included all studies with ≥100 patients reporting data on AHREs incidence. Pooled prevalence and incidence rates were computed; we also performed meta-regressions for pooled incidence rates, according to relevant study-level characteristics. This study was registered in PROSPERO: CRD42019106994. Results Among the 2,515 results retrieved, we included 51 studies in the systematic review and meta-analysis, with a total of 68,414 patients. Meta-analysis of included studies showed a pooled prevalence of 28.2% (95% CI: 24.3–32.5%, I2=99%), with a pooled incidence rate (IR) of 15 new AHRE cases per 100 patient-years (95% CI: 12–19, I2=100%). Given the large heterogeneity showed in the pooled estimates we performed additional analyses. Regarding pooled prevalence, we performed several subgroup analyses, according to various studies baseline characteristics, which did not show any significant difference in any of the subgroups examined. Regarding IR, a multivariable meta-regression analysis showed that decreasing follow-up time and increasing age were the only factors significantly associated with AHRE incidence, explaining a large proportion of heterogeneity (R2=68%, p Conclusions This systematic review and meta-regression demonstrated that SCAF is very common in patients with CIEDs, with an overall IR for AHREs of up to 15 per 100 patient-years; increasing with age and decreasing with longer follow-up time. Presence of SCAF was associated with an overall higher clinical risk profile compared to those subjects without SCAF. Funding Acknowledgement Type of funding sources: None. Figure 1. Meta-regression for AHRE Incidence

Funding Acknowledgements Type of funding sources: None. OnBehalf ESC-EHRA EORP AF General Long-Term Registry Investigators Introduction Data derived from recent observational studies in atrial fibrillation (AF) show how the complexity of the clinical phenotype, beyond baseline thromboembolic risk, can increase risk of major adverse outcomes. Importantly, risk factors tend to occur in clusters, rather than occur individually in isolation. Aims To describe AF patients’ clinical phenotypes among a large contemporary European AF cohort and to analyse the differential impact of these clinical phenotypes on the occurrence of major adverse outcomes. Methods We performed a hierarchical cluster analysis based on Ward’s Method and using Squared Euclidean Distance using 22 clinical covariates. All variables were considered as binary. Examining the distances between cluster coefficients and by visual inspection of the dendrogram produced we identified the optimal number of clusters. Patients with data available for all 22 variables were included. We considered occurrence of cardiovascular events and all-cause death. Results Among the original 11096 patients included, 9363 (84.4%) were available for this analysis. The cluster analysis identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients with prevalent noncardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients mainly admitted for first detected and paroxysmal AF with low prevalence of concomitant conditions; Cluster 3 (n = 2955; 31.6%) included patients with high prevalence of permanent AF, cardiac risk factors and comorbidities. Thromboembolic and bleeding risks were higher in Cluster 3 and progressively lower in Cluster 1 and Cluster 2 (both p Conclusions In European AF patients, three main clinical clusters were identified, those with non-cardiac comorbidities, low risk and cardiac comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of cardiovascular events and all-cause death. Abstract Figure. Kaplan-Meier Curves for Outcomes

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.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Abbott Vascular Int. (2011–2014), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2017), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2017), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2018). The Atrial Fibrillation NETwork (AFNET), conducting the registry in Germany, received support from The Bristol Myers Squibb/Pfizer Alliance (2014–2018) and the German Centre for Cardiovascular Research (DZHK). Funding from Daiichi-Sankyo and Boehringer-Ingelheim have been received for conducting the registry in Spain. Funding from BMS-Pfizer Alliance was received to support the programme in France Background The 4S-AF scheme (Stroke risk, Symptom severity, Severity of atrial fibrillation [AF] burden, Substrate severity) has recently been described as a novel approach to in-depth characterization of AF, and included in the 2020 European Society of Cardiology guidelines for the management of AF. Purpose In the present study, we validated for the first time the 4S-AF scheme in the Spanish and French cohorts of the EurObservational Research Programme (EORP)-AF Long-Term General Registry. Methods The Spanish and French cohorts of the EORP-AF Long-Term General Registry, were merged and included. The baseline 4S-AF scheme was calculated as follows: Symptom severity (according to EHRA symptom score: 0-2 points), Severity of AF burden (according to AF type: 0-3 points), Substrate severity (according to comorbidities/cardiovascular risk factors: 0-7 points); and related to the primary management strategy (rhythm or rate control). According to the results for these 3 domains, four code colors have been defined. Patients with all domains in "green" should be managed by rhythm control. In patients with one domain in "yellow" or two domains in "green" categories, rhythm control can be attempted. On contrary, for patients with "red" color category, the 4S-AF scheme suggests a rate control strategy. All-cause mortality and the composite of ischemic stroke/transient ischemic attack/systemic embolism, major bleeding and all-cause death, were the primary endpoints. These outcomes were recorded during 1-year of follow-up. Results 1479 patients (36.9% females, median age of 72 [IQR 64-80] years) were included (Table 1). The median 4S-AF scheme score was 5 (IQR 4-7). The 4S-AF scheme, as continuous and as categorical, was associated with the management strategy decided for the patient (both p Conclusion Characterization of AF by using the 4S-AF scheme may aid in identifying AF patients that would be managed by rhythm or rate control, and could also help in identifying high-risk AF patients for worse clinical outcomes in a ‘real-world’ setting. Abstract Table 1 and Figures 1A-1B

Funding Acknowledgements Type of funding sources: None. Introduction The ESC-EHRA EORP AF General Long-Term Registry provides a contemporary snapshot of European atrial fibrillation (AF) patients’ characteristics and management. Aims: We present data about the final 2-years follow-up observation of AF patients enrolled in the ESC-EHRA EORP AF General Long-Term Registry. Methods A contemporary evaluation of residual risk of adverse outcomes in a cohort of largely anticoagulated AF patients according to the baseline thromboembolic and bleeding risk, defined according to CHA2DS2-VASc and HAS-BLED scores. We determined cardiovascular (CV) events, CV death and all-cause death as outcomes. Results Among the original 11069 patients enrolled, 8409 (76.0%) patients had available follow-up status at the end of the 2-years follow-up. Patients age, female sex and most comorbidities were progressively more prevalent across the spectrum of thromboembolic and bleeding risk. Data on adverse outcomes were available for 10087 (91.1%), over the 2-year observation period. Outcome rates were progressively higher across CHA2DS2-VASc and HAS-BLED scores (all p Conclusions In this large contemporary European-wide cohort of AF patients, both baseline thromboembolic and bleeding risks were associated to an increased risk of major clinical outcomes. Both scores are reflective of high risk clinical states, and are predictive of major adverse outcomes even in a large cohort of largely anticoagulated patients with a lower residual risk of adverse outcomes. Abstract Figure.

Introduction The impact of body mass index (BMI) on outcomes in patients with atrial fibrillation (AF) has been largely debated. Aims To describe the relationship between BMI categories and clinical outcomes in a large cohort of European AF patients. Methods We included all AF patients with available baseline BMI and creatinine clearance and 1-year follow-up data enrolled in the EORP-AF General Long-Term Registry. Outcomes considered were: i) a composite of any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death; ii) CV death; iii) all-cause death. Results A total of 7,759 patients were included in this analysis. Of these, 55 (0.7%) were underweight, 2,074 (26.7%) were normal weight, 3,170 (40.9%) were overweight, 1,703 (21.9%) were obese and 757 (9.8%) were severe obese. Mean age was progressively lower across the categories (p Conclusions In a large cohort of European AF patients a progressively lower rate of outcomes was found across increasing BMI classes. After full adjustments, no significant association was found between the higher BMI classes and outcomes. Underweight was associated with an increased risk for CV death and all-cause death. Figure 1. Outcomes at 1-year Follow-up Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies have supported it with unrestricted grants

Background Natural history of atrial fibrillation (AF) shows a progression of arrhythmia from non-permanent to permanent AF. Permanent AF was found associated with a worse prognosis than non-permanent one. Aim To assess the factors associated with progression to permanent AF in an unselected population of AF patients with non-permanent AF. Methods In this prospective study we enrolled in- as well as out-patients with non-permanent AF and age ≥18 years, with at least one episode of ECG-documented AF within 1 year. The patients were followed-up at 1 month and every 6 months thereafter. Results Out of 523 patients, 314 (60%) were in non-permanent AF (80 [25.5%] paroxysmal AF, 165 [52.5%] persistent AF, 69 [2%] first diagnosed AF), mostly male (188, 59.9%), median age 71 years (IQ range 62–77), median CHA2DS2VASc 3 (1–4), median HATCH score 1 (1–2). After a median follow-up of 701 (IQ range 437–902) days, 66 patients (21%) showed permanent AF. CHA2DS2VASc and HATCH scores were incrementally associated to progression to permanent AF (CHA2DS2VASc χ2 p=0.001; HATCH χ2 p=0.017; p for trend CHA2DS2VASc At multivariable Cox proportional hazard regression the following variables were significantly associated with AF progression: age (hazard ratio [HR] 1.041; 95% CI: 1.004–1.079; p=0.028), at least moderate left atrial (LA) enlargement (>42 ml/m2) (HR 2.092; 95% CI: 1.132–3.866; p=0.018), antiarrhythmics drugs after the enrollment (HR 0.087; 95% CI: 0.011–0.662; p=0.018), EHRA score >2 (HR 0.351; 95% CI: 0.158–0.779; p=0.010) and Valvular HD (HR 2.161; 95% CI: 1.057–4.420; p=0.035). Adding LA dilation to HATCH score (HATCH-LA) and assigning 2 points based on multivariable Cox regression, HATCH-LA was statistically better in ROC curves in prediction of AF progression vs HATCH score (area under the curve 0.695 vs 0.636; DeLong p=0.0225). Survival-free curves on freedom from permanent AF using as discriminator HATCH-LA score ≤2 vs >2 led to a statistically significant difference (χ2=16.080 p Conclusions In patients without permanent AF, progression of AF was independentely related to age, LA dilation, AF symptoms severity, antiarrhythmic drugs and Valvular HD. HATCH score predicted AF progression and adding to it LA dilation (at least moderate) improved patients stratification for the risk of evolution to permanent AF. Funding Acknowledgement Type of funding source: None

Introduction Frailty is a major health determinant for cardiovascular disease. Thus far, data on frailty in patients with atrial fibrillation (AF) are limited. Aims To evaluate frailty in a large contemporary cohort of European AF patients, the relationship with oral anticoagulant (OAC) prescription and with risk of all-cause death. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. A 38-items frailty index (FI) was derived from baseline characteristics according to the accumulation of deficits model proposed by Rockwood and Mitnitsky. All-cause mortality was the primary study outcome. Results Out of the 11096 AF enrolled patients, data for evaluating frailty were available for 6557 (59.1%) patients who have been included in this analysis (mean [SD] age 68.9 [11.5], 37.7% females). Baseline median [IQR] CHA2DS2-VASc and HAS-BLED were 3 [2–4] and 1 [1–2], respectively. At baseline, median [IQR] FI was 0.16 (0.12–0.23), with 1276 (19.5%) patients considered “not-frail” (FI Conclusions In a European contemporary cohort of AF patients the burden of frailty is significant, with almost 1 out of 5 patients found to be “frail”. Frailty influenced significantly the choice of OAC therapy and was associated with (and predictive of) all-cause death at follow-up. Kaplan-Meier Curves Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies have supported it with unrestricted grants.

Background While the beneficial effects of cardiac resynchronization therapy (CRT) have been widely investigated soon after CRT implantation, relatively few data are available on long-term clinical outcomes of CRT recipients. Aim To investigate long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders and non-responders according to radionuclide angiography. Methods Consecutive heart failure patients with non-ischemic dilated cardiomyopathy undergoing CRT implantation at our University Hospital between 2007 and 2013 were enrolled. All patients were assessed with equilibrium Tc99 radionuclide angiography at baseline and after 3 months of CRT. Left ventricular (LV) ejection fraction was computed on the basis of relative end-diastolic and end-systolic counts, and intraventricular dyssynchrony was derived by Fourier phase analysis. Response to CRT was defined by an absolute increase in LV ejection fraction (LVEF) ≥5% at 3-month follow-up. Clinical outcome was assessed after 10 years through hospital records review. Results Forty-seven patients (83% men, 63±11 years) were included in the study. At 3 months, 25 (53%) patients were identified as CRT responders according to LVEF increase (from 26±8 to 38±12%, p Conclusions Although late overall mortality of non-ischemic CRT recipients was not significantly different between mid-term responders and non-responders, CRT responders were at lower risk of worsening heart failure death. Funding Acknowledgement Type of funding source: None

Background Atrial fibrillation (AF) is a frequent arrhythmia in pacemaker patients and is associated with poor quality of life and increased risks of heart failure, dementia, stroke, and death. The MINERVA trial has shown that the combination of 3 pacing algorithms – 1) atrial antitachycardia pacing (aATP), 2) atrial preventive pacing and 3) managed ventricular pacing (MVP) - delays progression to persistent and permanent AF, compared with standard DDDR pacing mode and with MVP mode, in pacemaker patients with AF history. Purpose We performed a comparative non randomized evaluation to confirm the hypothesis that aATP is the main driver of persistent/permanent AF reduction independently on the effect of preventive atrial pacing. Methods Thirty-one Italian and Japanese Cardiology centers included consecutive dual-chamber pacemaker patients with AF history. aATP was programmed in all patients while preventive atrial pacing was not enabled. Comparison was made with all the 3 groups in MINERVA randomized trial. The main endpoint was incidence of AF longer than 7 consecutive days, as detected by device diagnostics. Results A total of 146 patients (73 years old, 54% male) were included and followed for a median observation period of 31 months. The 2-year incidence of AF>7 days was 12% in the aATP group, very similar to that found in the arm of the MINERVA trial with aATP enabled (13.8%, p=0.732) and significantly lower than AF incidence found in the MINERVA Control DDDR arm (25.8%, p=0.012) and in the MINERVA MVP arm (25.9%, p=0.025). Conclusions In a real-world population of dual-chamber pacemaker patients with AF history, use of aATP was associated with low incidence of persistent AF during follow up, highlighting that the positive results of the MINERVA trial are related to the effectiveness of aATP rather than to the effects of preventive atrial pacing. Funding Acknowledgement Type of funding source: None

Background Physical activity (PA) may have a beneficial contribution for outcomes in patients with atrial fibrillation (AF). Purpose We aimed to evaluate the impact of self-reported PA in a large contemporary cohort of European AF patients on the risk of all-cause mortality. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Self-reported PA was categorized, on the basis of reported time spent exercising, as follows: i) No PA; ii) Occasional PA; iii) Regular PA; iv) Intense PA. The primary outcome was all-cause death. Results Over 11096, a total of 8699 (78.4%) patients (mean age (SD) 69.1 (11.5); 40.7% female) had available data about PA and follow-up observation and were included in the analysis. Of these, 3703 (42.6%) reported no PA, 2829 (32.5%) occasional PA, 1824 (21.0%) regular PA, with only 343 (3.9%) reporting intense PA. With the 4 increasing PA categories, mean age, proportion of female patients, CHA2DS2-VASc and HAS-BLED scores were progressively lower (all p Conclusions In a large contemporary cohort of European AF patients, self-reported PA was found to be inversely associated with all-cause death and CV death. Kaplan-Meier Curves Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP, several companies have supported the programme with unrestricted grants

Purpose In patients affected by heart failure an association exists between sleep apnea (SA) measured by polysomnography and adverse outcome. Impedance-based implantable cardioverter defibrillator (ICD) algorithms have been designed to compute the Respiratory Disturbance Index (RDI) to identify severe SA. The purpose of the DASAP-HF study was to evaluate the accuracy of RDI for the prediction of severe SA, and investigate the prognostic value of device-detected RDI values. Methods Patients with left ventricular ejection fraction ≤35% implanted with an ICD were enrolled and followed for 24 months. One month after implantation, patients underwent a polysomnographic study (PS) for assessing the apnea-hypopnea index (AHI). The average RDI value was calculated over a 1-week period preceding the sleep study and compared with the assessment of severe SA at PS (AHI ≥30 episodes/h). The endpoint was all-cause death after 24 months. Results 224 out of 265 enrolled patients had usable RDI values. Patients characteristics: 79% male, 67±10 years, BMI 27±7kg/m2, ejection fraction 29±5%, 54% ischemic cardiomyopathy, 50% CRT-D. The mean AHI value at PS was 21±15 episodes/h. The mean RDI value recorded during the week preceding PS was 30±16 episodes/h. RDI values accurately identified severe SA diagnosed at PS (AUC 0.77; 95% CI 0.70–0.83; P=0.001). Based on the ROC curve analysis, RDI ≥29 episodes/h and AHI ≥17 episodes/h maximized sensitivity and specificity for the prediction of death. Both indexes were independently associated with all-cause death but, after correction for the other independent significant prognostic variables, RDI≥29episodes/h yielded stronger prediction (HR: 12.22, 95% CI:1.64–91.37, p=0.015) as compared to AHI ≥17episodes/h (HR: 4.14, 95% CI:1.17–14.66, p=0.028). Moreover, severe SA diagnosed at PS (AHI ≥30episodes/h) was not associated with death (HR: 1.20, 95% CI:0.3817–3.8266, p=0.761). Conclusions In heart failure patients indicated to ICD, severe SA was confirmed to be associated with survival. The ICD-measured RDI accurately identified severe SA detected at PS, and was associated with the risk of death at long-term. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boston Scientific

Introduction Increasing age is a well-known determinant for incident atrial fibrillation (AF) as well as for adverse outcomes. With a progressively ageing population in Europe (and elsewhere), contemporary data are needed to investigate the impact of age in relation to major adverse events in AF patients. Purpose To evaluate the impact of increasing age on major adverse outcomes in a contemporary European AF cohort. Methods Patients enrolled in the EORP-AF Long Term General Registry were categorized by age: Results Among the 9762 patients included in this analysis, 2946 (30.2%) were Conclusions In a large contemporary cohort of European AF patients, increasing age was a major determinant of major adverse outcomes. Figure 1. Kaplan-Meier Curves for All-Cause Death Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies supported its activities with unrestricted grants.

Background Atrial fibrillation (AF) significantly impacts on patients' quality of life (QoL). An impaired QoL has been associated with worse outcomes even in AF patients, but contemporary data in a large-scale pan-European population are limited. Purpose We aimed to assess temporal changes in AF patients' QoL across 2 years follow-up observation, and the relationship of QoL changes with all-cause death. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. The EQ-5D-5L questionnaire was used to assess QoL. A Health Utility Score (HUS), indicating the overall health state (1 equals perfect health), was derived. Differences throughout the follow-up (Baseline, 1-Y FU, 2-Y FU) observation were assessed. The study outcome was all-cause mortality. Results Out of a total of 11906 patients, 8097 (73.0%) were available for this analysis. Mean (SD) age was 69.1 (11.5) years; 60.8% males; median CHA2DS2-VASc and HASBLED scores were 3 (IQR 2–4) and 1 (1–2), respectively. The mean (SD) HUS at baseline was 0.815 (0.200) and 0.834 (0.196), 0.829 (0.195) at 1-year follow-up and 2-year follow-up, respectively (p Conclusions In a contemporary European-wide cohort of AF patients, significant temporal changes in QoL were found. Patients at higher stroke risk according to CHA2DS2-VASc score showed a significant reduction in the QoL. Age and CAD were independently associated with changes in QoL. A greater reduction in HUS (i.e. worsening QoL) over time was associated with a higher risk of all-cause death. Temporal changes in HUS Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP, several companies have supported the programme with unrestricted grants

Background Outcome of Mitral Valve Prolapse (MVP) was controversial for long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of theme were also published to late '80 of the last century till early '00. Purpose To make a contemporary survey on the incidence of cardiovascular events in a selected population of patients affected by primary MVP referred to a tertiary cardiovascular center for the medical and surgical care of valvular heart disease. Methods We reviewed our MVP database; patients with at least 2 cardiologic evaluations inclusive of echocardiographic examination and at least 6 months follow up were enrolled. A total of 250 patients (126 F) were selected. Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up time was 100 months (8,33 yrs). Results At the first medical and echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR), 104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP (94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%) and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior mitral annulus diameter was 37 mm. During the follow up 7 patients died of non-cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture occurred during the follow up in most cases concerning mitral chordae linked to posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an evolution of the clinical condition of 48 patients (19.2%) which developed Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at the initial evaluation). A total of 45 patients (18%) underwent mitral valve surgery. 40 needed in-hospital treatment in most cases due to the development of atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6 (2.4%). The overall cardiovascular event rate was 4,33/100 patients-year, significantly higher than reported in community based studies. Conclusions The prognosis of a MVP population referred to a tertiary cardiovascular center is not benign. The most frequent complications are progression of MR and MV surgery. Sudden death is also more frequent than in general population. More studies are needed to identify what patients with MVP are at risk for it.

Background The number of patients with cardiac implantable electronic devices (CIED) requiring a radiation therapy (RT) for cancer treatment is increasing over time. Nevertheless, the rate and predictors of CIED malfunctions are still controversial. Purpose The aim of our study is to estimate the prevalence and possible predictors of RT-related CIED malfunctions and to describe malfunction characteristics. Methods We retrospectively reviewed medical records of all pacemaker (PM)/implantable cardioverter defibrillator (ICD) patients who underwent RT at our centre between January 2004 and July 2018. We included data from the CIED interrogation performed before the RT course to the first interrogation after the end of the RT course. As a safety measure, during RT a magnet was applied to every ICD and, in all PM-dependent patients, the device was temporarily reprogrammed in V00. Device relocation from the RT field was performed in 2/150 (1.3%) RT courses. Results One hundred twenty-seven patients were included, who underwent 150 separate RT courses. Eighty one percent of patients had a PM, while 19% had an ICD. Of note 17.4% of patients were PM-dependent. Neutron producing RT was used in 37/139 (26.6%) patients, whereas marginal neutron producing and non-neutron producing RT was used in 9/139 (6.4%) and 93/139 (67%) patients respectively. The cumulative dose (Dmax) delivered to the CIED exceeded 5Gy only in 2/132 (1.5%) cases. Three device-related malfunctions were found (2%). None of them were life-threatening or lead to a clinical event. All dysfunctions were resolved by reprogramming the device and did not require CIED substitution or leads extraction. Details of dysfunctions included: 1) a partial reset of an ICD, leading to self-reprogramming in safety mode, 2) full reset of a PM, which required the re-initialisation of the device and 3) programming change of the magnetic PM frequency to 30bpm (instead of 90 bpm). In all cases the Dmax delivered to the CIED was Conclusions In accordance with the current literature, our results show that RT in patients with CIED is substantially safe. Malfunctions are uncommon and do not result in clinical events, but can develop even if the Dmax delivered to the CIED is

Aim To look for differences in cardiac phenotype and natural history of patients affected by laminopathy, according to the presence or less of neuromuscular involvement at clinical presentation. Methods We prospectively analyzed 47 consecutive pts with a genetic diagnosis of laminopathy followed at a single centre between 1994 and 2017. Additionally, reports of clinical and instrumental evaluations before referral at our centre were retrospectively evaluated. Results Neuromuscular presentation, mainly as Emery-Dreifuss muscular dystrophy (EDMD), was present in 21 (46%) cases (14 LMNA and 7 EMD gene mutations). These pts had symptoms earlier (9 vs 39 years, p Conclusions In pts affected by laminopathy neuromuscular involvement, when present, was most often the first clinical manifestation and preceded cardiological involvement, with a long time frame in some cases. Except for sinus node dysfunction, much more frequent in patients with EDMD, a similar prevalence of rhythm disturbances was reported, although pts with neuromuscular clinical onset were younger at diagnosis of AF and at PM implantation. Pts without neuromuscular presentation had a higher prevalence of CMP and ventricular arrhythmias, albeit a similar rate of heart transplantation. In pts with neuromuscular onset, cardiac involvement was characterized by a stepwise progression from rhythm disturbances to CMP, where a strict temporal progression from rhythm disturbances to CMP was not observed in the group of pts without neuromuscular clinical onset.

Background Renal function is an important predictor of major adverse outcomes in the general population. In the setting of atrial fibrillation (AF), renal dysfunction may act both as a risk factor and a proxy of vascular risk factors and comorbidities. Methods We analyzed the association of renal function, as estimated glomerular filtration rate (eGFR) using the CKD-EPI formula, with 1-year outcomes in a “real-world” cohort of European AF patients from the EORP-AF Long-Term General Registry. Results 7725 were available for this analysis. Of these, 1294 (16.7%) had normal renal function (≥90 mL/min/1.73 m2), 3848 (49.8%) mildly reduced renal function (60–89 mL/min/1.73 m2), 2311 (29.9%) moderately reduced renal function (30–59 mL/min/1.73 m2) and 272 (3.5%) severely reduced renal function ( Any TE/ACS/CV Death CV Death All-Cause Death mL/min/1.73 m2 HR (95% CI) HR (95% CI) HR (95% CI) eGFR ≥90 (ref.) – – – eGFR 60–89 0.99 (0.67–1.46) 0.81 (0.44–1.51) 0.74 (0.47–1.19) eGFR 30–50 1.12 (0.74–1.69) 1.00 (0.53–1.89) 0.95 (0.59–1.54) eGFR Conclusions In AF patients, impaired renal function at baseline is associated with a progressive increase in the risk of major adverse outcomes during follow up. Severe renal dysfunction is an independent predictor of all the adverse outcomes.

Introduction Heart failure (HF) is a well-known risk factor for atrial fibrillation (AF). Moreover, HF is associated with worse clinical outcomes in patients with known AF. Recently, phenotypes of HF have been redefined according to the level of ejection fraction (EF). New data are needed to understand if a differential risk for outcomes exists according to the new phenotypes' definitions. Purpose To evaluate the risk of major adverse outcomes in patients with AF and HF according to HF clinical phenotypes. Methods We performed a subgroup analysis of AF patients enrolled in the EORP-AF Long-Term General Registry with a history of HF at baseline, available EF and follow-up data. Patients were categorized as follows: i) EF Results A total of 3409 patients were included in this analysis: of these, 907 (26.6%) had HFrEF, 779 (22.9%) had HFmrEF and 1723 (50.5%) had HFpEF. An increasing proportion with CHA2DS2-VASc ≥2 was found across the three groups: 90.4% in HFrEF, 94.6% in HFmrEF and 97.3% in HFpEF (p Cox Regression Analysis HR (95% CI) Any TE/ACS/CV Death CV Death All-Cause Death HFmrEF 0.65 (0.49–0.86) 0.53 (0.38–0.74) 0.55 (0.41–0.74) HFpEF 0.50 (0.39–0.64) 0.42 (0.31–0.56) 0.45 (0.35–0.59) ACS = Acute Coronary Syndrome; CI = Confidence Interval; CV = Cardiovascular; EF = Ejection Fraction; HF = Heart Failure; HR = Hazard Ratio. Conclusions In this cohort of AF patients with HF, HFpEF was the most common phenotype, being associated with a profile related to an increased thromboembolic risk. Compared to HFrEF, both HFmrEF and HFpEF were associated with a lower risk of all major adverse outcomes in AF patients.

Background Atrial fibrillation (AF) is the most prevalent heart rhythm disorder in clinical practice and it is associated with poor quality of life and increased risks of heart failure, dementia, stroke, and death. Moreover AF management is a huge cost for healthcare systems. AF is irregular, typically originates from the pulmonary veins, and as such, requires cardioversion to terminate persistent episodes. AF is not susceptible to pace-termination, however, the MINERVA trial has shown that AF may transform in slower organized rhythms such as atrial flutter or atrial tachycardia, which can often be terminated by atrial anticahycardia pacing (ATP); in particular by Reactive ATP, a specific ATP feature which can be re-armed when atrial arrhythmias get slower or more regular. The MINERVA trial showed that the combination of ATP, preventive atrial pacing algorithms and minimal ventricular pacing (MVP) was associated with lower progression to persistent and permanent AF, compared with standard DDD pacing mode and to MVP mode, in pacemaker patients with clinical history of AF. Purpose We aimed to confirm MINERVA trial results in real-world clinical practice and to evaluate whether AF prevention was associated with preventive atrial pacing or solely with ATP. Indeed in our project atrial preventive pacing algorithms were not enabled and the pacing mode (DDD or MVP) was chosen according to patients' AV conduction characteristics. Methods Consecutive dual-chamber pacemaker patients with sinus node disease and device detected AT/AF were prospectively followed by 30 Italian cardiologic centers in an observational research. Clinical and device data were collected and reviewed by expert cardiologists to assess AT/AF occurrence through in clinic visit and/or remote transmissions of device data. Results A total of 239 patients (73 years old, 56% male) wearing a dual-chamber pacemaker with Reactive ATP were included in the project, followed for a median observation period of 13 months and compared with 1145 patients included in the MINERVA trial followed for a median observation period of 34 months and programmed with DDD pacing mode (383 patients), MVP (389 patients) and MVP+Reactive ATP+preventive algorithms (373 patients). As shown in the following figure incidence of 7 consecutive days of AF in the patients treated by DDD/MVP+Reactive ATP in real-world clinical practice was very similar to that found in the MINERVA trial arm programmed with MVP+Reactive ATP+preventive algorithms. Incidence of AF longer than 7 days Conclusions Our analysis performed in a population of sinus node disease patients with dual-chamber pacemakers confirmed MINERVA trial results in terms of prevention of long-lasting AF episodes. In particular these results confirm the benefit associated with the use of Reactive ATP, rather than preventive atrial pacing algorithms.