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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The PREVEND study is supported by the Dutch Kidney Foundation and the Netherlands Heart Foundation. Background Atrial fibrillation (AF) is a condition that occurs in the presence of comorbidities. With the accumulation of comorbidities over time, certain comorbidities may more often occur together than others, i.e. clustering of comorbidities. Acknowledging clustering of certain comorbidities may have implications for diagnosing previously unrecognized comorbidities, and clusters of comorbidities may carry differential risks of diseases, like AF. Albeit that the individual cardiovascular risk factors and comorbidities are well known, information on the impact of clustering of these on incident AF is sparse. Purpose We aimed to investigate the presence of clusters of cardiovascular and renal comorbidities and study the association between comorbidity clusters and incident AF. Methods We used the community-based Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort in which 8,592 individuals participated. We excluded individuals with prior AF or missing ECG data, leaving 8,265 individuals for analysis. Atrial fibrillation was diagnosed if either AF or atrial flutter was present on a 12-lead ECG during one of the study visits, or at an outpatient visit or hospitalization. Latent class analysis was performed to assess clustering of 10 cardiovascular and renal comorbidities. The optimum number of classes was determined by the number of classes for which the Bayesian information criterion (BIC) reached a minimum value. As secondary analysis, latent class analysis was repeated with additionally including age, sex, and ethnicity. Kaplan-Meier analysis was performed to calculate the cumulative probability of incident AF, stratified by the latent classes. Results In the total population, the mean age was 48.9±12.6 years and 50.2% were women. During 9.2±2.1 years of follow-up, 251 individuals (3.0%) developed AF. Latent class analysis resulted in a model with three clusters as the optimal model, with one cluster being young (44.5±10.8 years) and healthy, carrying a low (1.0%) risk of incident AF; one cluster being older (63.0±8.4 years) and multimorbid, carrying a high (16.2%) risk of incident AF and a third middle-aged (57.0±11.3 years), obese and hypertensive cluster carrying an intermediate risk (5.9%) of incident AF. When adding age, sex and ethnicity to the latent class analysis, similar results were observed. Conclusion We identified three clusters of individuals in the community-based PREVEND cohort. The three clusters contained different amounts of comorbidities carrying different risks of incident AF. However, there were no differences between clusters regarding specific combination(s) of comorbidities.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, and grant support from Medtronic to the institution. MHJPF was funded by a grant from the Karen Elise Jensen Foundation. JCN was supported by a grant from the Novo Nordisk Foundation Background Atrial fibrillation (AF) has been associated with adverse events and constitutes a significant, global healthcare challenge. Paucity exists on the occurrence of brady- and ventricular tachyarrhythmias. Purpose The aim of this predefined sub-analysis of the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling, and Vascular destabilization in the progression of AF (RACE V) study was to examine the prevalence of brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF). Methods We identified 417 patients with PAF and at least two years of follow-up in RACE V; 25 patients with pacemakers at baseline were excluded. All remaining patients (n=392) received an implantable loop recorder and performed daily automated and weekly manual transmissions. Throughout follow-up, all detected episodes of tachycardia ≥182 BPM (cycle length ≤330ms) of ≥24 beats, bradycardia ≤30 BPM (cycle length ≥2000ms) of ≥12 beats, and pauses ≥5 seconds were adjudicated by three cardiologists. Results Over 1,272 patient years of continuous rhythm monitoring, we validated 1,940 episodes in 175 patients with paroxysmal self-terminating PAF (45%); 106 (27%) patients experienced AF or atrial flutter (AFL) with a rapid rate, pauses ≥5 seconds or bradycardias ≤30 BPM occurred in 47 (12%) patients (figure 1), and in 22 (6%) patients, both rapid AF/AFL and bradyarrhythmias were observed. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.4, 95% CI 1.4-3.9), longer PQ interval (HR 1.9, 1.1-3.1), CHA2DS2-VASc score ≥2 (HR 2.2, 1.1-4.5), and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. For tachyarrhythmia episodes, age >70 years was associated with a significantly lower tachyarrhythmia risk (HR 0.4, 95% CI 0.2-0.7) in the multivariable analysis. Conclusions In a cohort exclusive to patients with self-terminating PAF, severe bradyarrhythmia episodes or AF/AFL with rapid ventricular rates occurred in 45% of patients. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF.

Funding Acknowledgements Type of funding sources: None. Purpose To investigate whether there are differences between nondihydropyridine calcium channel blockers and beta blockers on heart rate in patients with paroxysmal and persistent atrial fibrillation (AF). Methods In present analysis of the AFFIRM trial, the effect of rate control drugs on heart rate was evaluated during first reported AF-episode as well as the last recorded sinus rhythm episode prior to AF. Patients who used both rate control drugs or switched rate control drugs between the last sinus rhythm and the first AF episode were excluded. Results A total of 1195 patients were in sinus rhythm at baseline and used either betablockers (603, 50%) or non-dihydropyridine channel blockers (592, 50%). Of the total, 513 had at least one episode of AF while remaining on the same rate control drug, 257 (50%) of them using calcium channel blockers and 256 (50%) of them using betablockers. Mean age of patients treated with a calcium channel blocker was 70±8 years versus 68±8 for the betablocker treated patients (p=0.014). Forty-four percent were women, 31% with paroxysmal AF, and 69% with persistent AF. A resting heart rate Conclusion In patients with persistent or paroxysmal AF included in the AFFIRM trial, nondihydropyridine calcium channel blocker as rate control treatment was associated with less bradycardia during sinus rhythm compared to betablockers. Resting heart rates

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): unrestricted grant from Abbott-Netherlands to the University Medical Center Groningen Introduction Atrial fibrillation (AF) and heart failure (HF) with preserved ejection fraction (HFpEF) commonly co-exist and both conditions are typically characterized by impaired left atrial (LA) function. While obesity is an important contributor to both AF and HFpEF, it has been suggested that specifically epicardial adipose tissue (EAT) may be involved in the pathophysiology of these diseases. However, data on the relation between EAT and atrial function using cardiac magnetic resonance imaging (MRI) is scarce. In this study we aimed to investigate the association of body mass index (BMI) and EAT with LA function in patients with HFpEF. Methods Patients with symptomatic HF and left ventricular ejection fraction >40% were enrolled. All patients underwent cardiac MRI. LA function was assessed using the cine long-axis 4-chamber and 2-chamber acquisitions. EAT volume was quantified on the short-axis cine-stacks and indexed for BSA. Patients were divided according to the presence of obesity (BMI >30 kg/m2) and by low and high EAT (i.e. >100 ml/m2). Results In total, 125 patients were included. Mean age was 71±10 years, 62 (50%) were women and mean BMI was 30±6 kg/m2. In total, 56 (45%) patients were obese, 56 (48%) had high EAT, 68 (54%) had a diagnosis of AF, 98 (78%) had hypertension, 48 (38%) had diabetes mellitus and 44 (35%) had coronary artery disease. There was no difference in LA end-systolic volume (63 vs. 59 ml/m2, p=0.6), LA emptying fraction (31 vs. 30%, p=0.9) and LA reservoir strain (15 vs. 14%, p=0.4) between obese and non-obese patients. However, when patients were divided according to EAT volume, patients with high EAT had higher LA end-systolic volume (67 vs. 56 ml/m2, p=0.01) and lower LA reservoir strain (12 vs 17%, p=0.03), as compared to patients with low EAT. LA emptying fraction was not significantly different between high and low EAT (38 vs. 33%, p=0.1). There was no significant correlation between BMI and LA end-systolic volume, LA emptying fraction and LA reservoir strain (data not shown). On the contrary, there was a significant correlation between EAT and LA end-systolic volume (r=0.3, p=0.002), LA emptying fraction (r= -0.2, p=0.01) and LA reservoir strain (r= -0.2, p=0.006). There were no differences in the presence of AF between obese and non-obese patients (57 vs 52%, p=0.6) and between high and low EAT (59 vs. 54%, p=0.6). Conclusion In patients with HFpEF, increased EAT but not obesity was associated with LA dysfunction. The cause effect relation between epicardial adipose tissue, atrial cardiomyopathy and the development of AF in patients with HFpEF need further investigation.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling, and Vascular destabilisation in the progression of AF (RACE V). Unrestricted grant support from Medtronic Trading NL B.V. Background Atrial fibrillation (AF) progression is associated with morbidity and mortality. Both comorbidities and symptom severity are pillars in the ABC treatment pathway as proposed by the ESC guidelines. Interaction between comorbidities, symptom severity and AF progression seems evident, but evidence is lacking. Aims The aim of the present study is to investigate whether the number of comorbidities is related with severity of AF symptoms, and whether AF symptom severity is associated with AF progression in patients with paroxysmal AF. Methods Patients Underwent extensive phenotyping at baseline and received continuous rhythm monitoring with an implantable loop recorder during follow-up. We studied the relation between comorbidities, AF symptom severity [quantified with the Toronto AF Severity Scale (AFSS)], and AF progression in patients with paroxysmal AF included in the RACE V study. Multivariate regression analysis was performed to study the association between comorbidities and AFSS tertiles, and the association between AF progression and AFSS tertiles. Results Of 417 paroxysmal AF patients, AFSS questionnaires at baseline were available in 403 patients (97%). Mean age was 65 (IQR 58-71) years, 174 (43%) were women. 132 patients (33%) reported a low score [score 0–2; lowest tertile (T1)], 129 patients (32%) reported a moderate score [score 3–7; middle tertile (T2)], and 142 (35%) reported a high score [score 8–35; highest tertile (T3)]. Patients with the most severe symptoms were older, more often women, more often had coronary artery disease, kidney dysfunction, and a higher body mass index (BMI). The number of comorbidities [defined as hypertension, heart failure, age >65 years, diabetes mellitus; coronary artery disease, BMI >25kg/m2, moderate or severe mitral valve regurgitation and kidney dysfunction (estimated glomerular rate (eGFR) Conclusions In paroxysmal AF, multimorbidity was associated with symptom severity and AF progression. However, symptom severity was not associated with AF progression.

Background Cryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI. Methods We included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase ≥ 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response. Results Following PVI, mean HR ± standard deviation increased in the entire group from 63.5 ± 8.4 to 69.1 ± 9.9 bpm at 3 months (p p p p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation. Conclusion Few patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year.

Introduction Achieving adequate rate control is a mainstay in the treatment of atrial fibrillation (AF). In the Rate Control versus Electrical Cardioversion Trial 7 – Acute Cardioversion versus Wait and See (RACE 7 ACWAS) trial, an early cardioversion approach was compared to a delayed cardioversion approach for patients with recent-onset symptomatic AF, followed by a four-week monitoring period using mobile health (mHealth). Purpose To assess the adequacy of rate control during recurrences of AF in the four weeks after an emergency department visit for recent-onset AF using mHealth. Methods After restoration of sinus rhythm (spontaneous or through cardioversion), patients (n=335) were asked to record one minute heart rate and rhythm recordings three times daily and in case of symptoms by using an electrocardiographic-based handheld device to monitor for recurrences for four weeks after the index visit. Recordings from the handheld device were collected at the end of the follow-up period. For this subanalysis, a cut-off for lenient rate control during AF recurrences was used and this was defined as a heart rate of Results mHealth-based monitoring identified 99 patients with a total of 314 recurrences (29.6% of the included patients; median age 67 [interquartile range (IQR) 13] years, 60.6% male, 49.5% delayed cardioversion group, median number of recurrences 2 [IQR 2]). Two recurrences in one patient were excluded from analysis because heart rate could not be adequately assessed due to too much interference. Rate control was always adequate during 126 recurrences (40.4%), always inadequate during 111 recurrences (35.6%) and varying between adequate and inadequate in the remaining 75 recurrences (24.0%). On a patient level, rate control was always adequate in 26 patients (26.5%), always inadequate in 20 patients (20.4%) and varying between or within recurrences in the remaining 52 patients (53.1%) (Figure 1). Although there were no differences in clinical characteristics of the patients based on their adequacy of rate control, there is a trend towards significance regarding randomisation group (p=0.051), with patients with adequate rate control being more often in the delayed cardioversion group compared to those with varying and inadequate rate control (18 (69.2%) vs 24 (46.2%) vs 7 (35.0%), respectively). Conclusion It is feasible to assess heart rate and the adequacy of rate control during recurrences of recent-onset AF using mHealth. Whether real time mHealth-based rate and rhythm monitoring can be integrated in a remote management pathway to adapt rate control in AF patients warrants further studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Health Research and Development–Health Care Efficiency Research Program

Introduction Pharmacological restoration of sinus rhythm (SR) in patients with symptomatic atrial fibrillation (AF) is expected to be accompanied by prompt alleviation of symptoms to avoid the need for electrical cardioversion (ECV) and/or hospitalization. The feasibility and safety of acute cardioversion of recent-onset (≤48 hours) symptomatic AF to SR with flecainide acetate oral inhalation (FlecIH) solution was shown in the Phase 2, open-label INSTANT trial. We examined symptoms, heart rate, time to discharge and need for ECV reported among patients in the INSTANT trial whose AF was successfully converted to SR (“conversion group”; N=25) versus those whose AF did not convert to SR (“no conversion group”; N=29). Methods Conversion success was determined using 12-lead Holter monitoring during a 90-minute observation period. Patients in the no conversion group were offered alternative treatment per the investigator discretion. Symptoms, vital signs, time to discharge, and the need for ECV were evaluated through Day 5. Results Data from 54 patients (33.3% female) with a mean age of 62.1 years and a mean BMI of 26.8 kg/m2 were analyzed. All patients reported at least one AF-related symptoms at baseline (palpitations=85%; dizziness=35%; shortness of breath=37%; chest discomfort=39%) and 83.3% presented with AF symptoms ≤24 hours in duration. At 90 minutes, 80.0% of the conversion group were asymptomatic compared to 37.9% of the no conversion group (p Conclusions Conversion of recent onset AF to SR with inhaled flecainide was associated with a reduction in symptoms, normalization of heart rate, rapid hospital discharge and avoidance of ECV during a 5-day follow-up period. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): InCarda Therapeutics

Background The development of atrial fibrillation (AF) is a complex multifactorial process. Over the past few decades, much has been learned about the pathophysiological processes that can lead to AF from a variety of specific disease models in animals. However, our ability to recognise these disease processes in AF patients is still limited, which has contributed to the limited progress in improving rhythm control in AF. Aims/objectives We believe that a better understanding and detection of the individual pathophysiological mechanisms underlying AF is a prerequisite for developing patient-tailored therapies. The RACE V Tissue Bank Project will contribute to the unravelling of the main molecular mechanisms of AF by studying histology and genome-wide RNA expression profiles and combining this information with detailed phenotyping of patients undergoing cardiac surgery. Methods As more and more evidence suggests that AF may occur not only during the first days but also during the months and years after surgery, we will systematically study the incidence of AF during the first years after cardiac surgery in patients with or without a history of AF. Both the overall AF burden as well as the pattern of AF episodes will be studied. Lastly, we will study the association between the major molecular mechanisms and the clinical presentation of the patients, including the incidence and pattern of AF during the follow-up period. Conclusion The RACE V Tissue Bank Project combines deep phenotyping of patients undergoing cardiac surgery, including rhythm follow-up, analysis of molecular mechanisms, histological analysis and genome-wide RNA sequencing. This approach will provide detailed insights into the main pathological alterations associated with AF in atrial tissue and thereby contribute to the development of individualised, mechanistically informed patient-tailored treatment for AF.

Background The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and Conclusion iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

In the past 20 years the Netherlands-based RACE trials have investigated important concepts in clinical atrial fibrillation (AF). Their scope ranged from rhythm versus rate control to early or delayed cardioversion and also included early comprehensive management of AF in two trials, one focusing on early ‘upstream therapy’ and risk factor management and the other on integrated chronic nurse-led care. Studies were mostly triggered by simple clinical observations including futility of electrical cardioversion in persistent AF; many patients with permanent AF tolerating day-after-day ‘uncontrolled’ resting heart rates of up till 110 beats/min; patients being threatened more by vascular risks than AF itself; and insufficient guideline-based treatments for AF. Also the observation that recent-onset atrial fibrillation generally converts spontaneously, obviating cardioversion, triggered one of the studies. The RACE trials shifted a number of paradigms and by that could change the AF guidelines. The initial ‘shock-and-forget’ attitude made place for increased attention for anticoagulation, and in turn, broader vascular risks were recognised. In a nutshell, the adage eventually became: ‘look beyond the ECG, treat the patient’. Electronic supplementary material The online version of this article (10.1007/s12471-020-01476-0) contains supplementary material, which is available to authorized users.

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

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Background Screening for atrial fibrillation (AF) improves detection of AF. However, it is unknown whether AF detected at screening carries risks similar to clinically detected AF, and if it should be treated similarly. Purpose We aimed to compare clinical outcomes in individuals with screen-detected vs. hospital-detected incident AF. Methods We studied 8265 individuals (mean age 49 ± 13 years, 50% women) without prevalent AF from the population-based PREVEND (Prevention of Renal and Vascular End-Stage Disease) cohort study. By design, 70% of PREVEND participants had urinary albumin concentration ≥10 mg/l. AF was considered screen-detected when first detected on a 12-lead electrocardiogram (ECG) during one of the PREVEND study visits, and hospital-detected when first detected on a hospital ECG. Using Cox regression models with screen-detected and hospital-detected AF as time-varying covariates, we studied the association of screen-detected vs. hospital-detected AF with mortality, incident heart failure (HF), and incident cardiovascular (CV) events. Results During a mean follow-up of 9.7 years, 265 participants (3.2%) developed incident AF (mean age 62 ± 9 years, 30% women, 65% hypertension, 23% obesity, 9% diabetes, 15% history of myocardial infarction, 3% history of stroke, 2% prevalent HF). Of all incident AF cases, 60 (23%) were screen-detected and 205 (77%) hospital-detected. Baseline characteristics were generally comparable between participants with screen-detected and hospital-detected AF. A larger proportion of incident AF was screen-detected in men (26%) compared to women (15%). In univariabe analysis, both screen-detected and hospital-detected AF were strongly associated with death, incident HF, and incident CV events. After multivariable adjustment, hospital-detected AF was significantly associated with death (HR 2.95, 95% CI 2.18-4.00), incident HF (HR 3.98, 95% CI 2.49-6.34), and incident CV events (HR 1.92, 95% CI 1.21-3.06). Screen-detected AF was significantly associated with death (HR 2.21, 95% CI 1.09-4.47) and incident HF (HR 4.90, 95% CI 2.28-10.57), but not with incident CV events (HR 1.12, 95% CI 0.46-2.71). Conclusions In a population-based cohort enriched for microalbuminuria, almost a quarter of incident AF cases was first detected through ECG screening. Compared to hospital-detected AF, screen-detected AF was similarly associated with adverse outcomes. Although randomised trials are needed, this study highlights that AF screening may help decrease the general burden of CV disease.

Background Combined 'hybrid' thoracoscopic and percutaneous atrial fibrillation (AF) ablation is a strategy used to treat AF in patients with therapy-resistant symptomatic AF. We aimed to study efficacy and safety of single-stage hybrid AF ablation in patients with symptomatic persistent AF, or paroxysmal AF with failed endocardial ablation, and assess determinants of success and quality of life.Methods We included consecutive patients undergoing single-stage hybrid AF ablation. First, we performed epicardial ablation, via thoracoscopic access, to isolate the pulmonary veins and superior caval vein and to create a posterior left atrial box. Thereafter, isolation was assessed endocardially and complementary endocardial ablation was performed, followed by cavotricuspid isthmus ablation. Efficacy was assessed by 12-lead electrocardiography and 72-hour Holter monitoring after 3, 6 and 12 months. Recurrence was defined as AF/atrial flutter/tachycardia recorded by electrocardiography or Holter monitoring lasting >30s during 1-year follow-up.Results Fifty patients were included, 57 +/- 9 years, 38 (76%) men, 5 (10%) paroxysmal, 34 (68%) persistent and 11 (22%) long-standing persistent AF. At 1-year 38 (76%) maintained sinus rhythm off antiarrhythmic drugs. Majority of recurrences were atrial flutter (9/12 patients). Success was associated with type of AF (p = 0.039). Patients with paroxysmal AF had highest success, patients with longstanding persistent AF had lowest success. Seven (14%) patients had procedure-related complications. Quality of life improved after ablation in patients who maintained sinus rhythm.Conclusion Success of single-stage hybrid AF ablation was 76% off antiarrhythmic drugs, being associated with type of AF. Quality of life improved significantly, Procedure-related complications occurred in 14%.

Background There is widespread interest in population-based screening for atrial fibrillation (AF). However, there is debate regarding the optimal screening method and duration. Objectives To estimate the incidence of short-duration AF detected by a single continuous 14-day electrocardiographic (ECG) monitor in older individuals without prior AF and to estimate the risk of ischemic stroke or systemic embolism associated with these episodes. Methods Pacemaker and defibrillator electrograms were reviewed from a cohort of individuals ≥65 years old, with a history of hypertension, but no prior AF. For each participant, we simulated a continuous 14-day ECG monitor by randomly selecting a 14-day window in the 6 months following enrolment and measured the total AF burden during that period. We repeated random sampling 1000 times to ensure a robust estimate of the likelihood of capturing AF in a single 14-day period. We used Cox proportional hazards models adjusted for CHA2DS2-VASc score to estimate the risk of ischemic stroke or systemic embolism associated with different burdens of AF. Results Among 2470 participants with at least 6 months of follow-up, the mean CHA2DS2-VASc score was 4.0±1.3. The proportion of participants with an AF burden of >6 min on a single 14-day monitor was estimated as 3.1%, while the proportion with burdens of >15 min and >30 min were 2.9% and 2.6%, respectively. Over a mean follow-up of 2.5 years, 44 participants had an ischemic stroke or systemic embolism; the rate among patients with an AF burden ≤6 mins was 0.70%/year. An AF burden >6 min was associated with an increased risk of stroke or systemic embolism (2.2%/year, HR 3.0; 95% CI 1.3–5.7), as were burdens >15 min (2.4%/year; HR 3.3; 95% CI 1.4–6.4) and >30 min (2.6%/year HR 3.5; 95% CI 1.5–6.7). Conclusion Approximately 3% of individuals aged 65 years and older and with hypertension may have previously undiagnosed asymptomatic AF detected by a single 14-day continuous ECG monitor. As little as 6 minutes of AF may be associated with an increased risk of stroke. Randomized clinical trials are required to definitively assess screening in this population. Funding Acknowledgement Type of funding source: None

Background Women are usually underrepresented in studies evaluating rhythm control strategies in patients with atrial fibrillation (AF). Subsequently, the same holds true for studies looking at predictors for success of a rhythm control strategy for AF. Purpose To study the predictive power of the non-invasively determined dominant frequency (DF) on the electrocardiogram (ECG) in men and women undergoing electrical cardioversion (ECV) for persistent AF. Methods We matched 105 female patients undergoing elective ECV for persistent AF and 105 male control patients based on age and cardiovascular comorbidity profile. We determined the DF on all 12 leads of a standard digital 10 seconds ECG recorded on the day of ECV. Recurrences of AF within the first year after ECV were documented. Results There were no differences in comorbidities, AF duration, left ventricular systolic function, indexed left atrial volume and anti-arrhythmic drugs between male and female patients. The dominant frequency was significantly lower in male patients without an AF recurrence on all leads. The best performing lead to identify patients with recurrences was lead III with an AUC 0.752. The optimal cut-off point was a DF Conclusion The non-invasively measured dominant frequency is able to predict AF recurrence after electrical cardioversion in male patients with persistent AF but not in a matched female cohort. This difference might be explained by different pathophysiological mechanisms underlying AF in male and female patients. Therefore, future research is needed on pathophysiological differences between men and women that can explain and might overcome these challenges. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Network for Translational Research in Atrial Fibrillation (grant no. 261057), the Center for Translational Molecular Medicine (COHFAR)

Aims Limited causal evidence is available on the relationship between body mass index (BMI) and atrial fibrillation (AF) progression. Sex differences have been noted and may be relevant for AF progression. We investigated the association between the BMI Genetic Risk Score (GRS) and AF progression in men and women of the Groningen Genetic Atrial Fibrillation (GGAF) cohort. Methods and results The GGAF cohort (n = 2207) is a composite of 5 prospective cohorts with individuals of European ancestry. AF patients with genetic information, with at least 12 months follow-up and AF progression data were included. AF progression was defined as progression from paroxysmal to persistent/permanent AF, or persistent to permanent AF. A BMI GRS was constructed of genetic variants associated with BMI. Univariate and multivariate Cox proportional hazard regression analyses were performed in the total population and in men and women, separately. During a median follow-up of 34 [interquartile range 19–48] months 630 AF patients (mean age 62±11, 36% women, BMI of 28±5) were analyzed, and men and women developed similar AF progression rates (respectively 6.5% versus 6.1%). The BMI GRS was not associated with AF progression either as a continuous variable or in tertiles in the overall population. However, the BMI GRS was associated with the tertile of the highest BMI GRS in women (n = 225), also after multivariable adjustments of clinical risk factors (Hazard ratio 2.611 (95% confidence interval 1.151–5.924) p = 0.022). Conclusions Genetically-determined BMI is only associated with women at risk of AF progression. The results may be supporting evidence for a causal link between observed BMI and AF progression in women. We emphasize the need for further investigation of genetically determined BMI and observed BMI to optimize AF management in women with increased risk for AF progression.

Funding Acknowledgements European Commission [FP7-242209-BIOSTAT-CHF], European Union’s Horizon 2020 under the Marie Skłodowska-Curie grant agreement No 754425 Background. Atrial fibrillation (AF) and heart failure (HF) are two growing epidemics that frequently co-exist, share clinical risk factors, and predispose to each other. There is limited understanding of the underlying pathophysiology of the combination of both conditions. Purpose. To perform pathway analyses of circulating plasma proteins and evaluate whether patients with both HF and AF have different activated pathways compared to those with HF without AF. Methods. We performed pathway overrepresentation analyses of differentially expressed plasma proteins in HF, with reduced (HFrEF) and preserved (HFpEF) ejection fraction, with AF versus sinus rhythm on ECG at enrolment in BIOSTAT-CHF, using 92 cardiovascular biomarkers. Pathway analyses were performed based on existing knowledge using Gene Ontology, REACTOME, and KEGG, to study underlying activated biological pathways. Resulting pathways were corrected by Bonferroni method. Results. We studied 2,839 patients with HF irrespective of their ejection fraction of whom 1,116 (39%) had AF and 1,723 (61%) were in sinus rhythm. HF patients with AF were older (76 ± 10 vs. 70 ± 12, p < 0.001), were less women (28% vs. 34%, p < 0.001), had history of stroke (16% vs. 10%, p < 0.001), renal disease (39% vs. 31%, p < 0.001) and less history of coronary artery disease (40% vs. 53%, p < 0.001). There were no significant differences in patients with hypertension (62% vs. 60 %, p = 0.22), diabetes (32% vs. 31%, p = 0.51) and COPD (18% vs. 16%, p = 0.20). A total of 1,661 (59%) had HFrEF and 432 (15%) had HFpEF. Pathway overrepresentation analyses revealed three amyloid-related pathways statically significant in total HF group, and in HFrEF and HFpEF respectively, with AF compared with those in sinus rhythm: amyloid-beta formation (p < 4.0E-4, p < 7.4E-6), amyloid-beta metabolic process (p < 1.0E-3, p Conclusion. Pathway analyses revealed activation of amyloid-beta pathways in HF patients with AF versus sinus rhythm with SPON-1, IGFBP-1 and IGFBP-7 overrepresented proteins. Amyloid-beta pathways may play a role in the pathophysiology of the combination of HF and AF, which needs to be replicated and validated in additional cohorts. Figure. Pathway analysis of activated proteins in patients with HF, HFrEF (A) and HFpEF (B) and AF versus sinus rhythm. Proteins are represented as dots and pathways as circumferences. Abstract Figure. Pathway overrepresentation analysis

Introduction: The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown.Methods and results: In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7-9.6] m/z versus 4.31 [3.2-6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14-0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210.

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

Cardiovascular implantable electronic devices (CIEDs) can detect atrial arrhythmias, i.e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in patients showing AHRE appears to be lower than in patients with clinical atrial fibrillation (AF) and it is unclear whether the former will benefit from oral anticoagulants. Based on currently available evidence, it seems reasonable to consider antithrombotic therapy in patients without documented AF showing AHRE >24 hours and a CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65-74 years and female sex) >= 1, awaiting definite answers from ongoing randomised clinical trials. In patients with AHRE

Atrial fibrillation (AF) is not benign. Cardiovascular diseases and risk factors differ importantly amongst patients. Careful phenotyping with the aim to start tailored therapy may improve outcome and quality of life. Furthermore, structural remodelling plays an important role in initiation and progression of AF. Therapies that interfere in the remodelling processes are promising because they may modify the atrial substrate. However, success is still limited probably due to variations in the underlying substrate in individual patients. The most favourable effects of lifestyle changes on success of rhythm control have been demonstrated in obese patients with AF. Differences in genotype may also play an important role. Common gene variants have been associated with recurrence of AF after electrical cardioversion, antiarrhythmic drug therapy and catheter ablation. Therefore, both phenotyping and genotyping may become useful for patient selection in the future. Beside the choice of rate or rhythm control, and type of rhythm control, prevention of complications associated with AF may also differ depending on genotype and phenotype. Efficacy of stroke prevention has been well established, but bleeding remains a clinically relevant problem. Risk stratification is still cumbersome, especially in low-risk patients and in those with a high bleeding risk. The decision whether to start anticoagulation (and if so which type of anticoagulant) or, alternatively, to implant an occlusion device of the left atrial appendage may also be improved by genotyping and phenotyping. In this review, we will summarize new insights into the roles of phenotype and genotype in generating more tailored treatment strategies in patients with AF and discuss several patient-tailored treatment options.

Objectives This study evaluated the waiting list for elective electrical cardioversion (ECV) for persistent atrial fibrillation (AF), focusing on when and why procedures were postponed. We compared the effects of management of the waiting list conducted by physicians versus management by nurse practitioners (NPs) and we evaluated the safety of our anticoagulating policy by means of bleeding or thromboembolic complications during and after ECV. Background Not all patients selected for ECV receive their treatment at the first planned instance due to a variety of reasons. These reasons are still undocumented. Methods We evaluated 250 consecutive patients with persistent AF admitted to our clinic for elective ECV. Results Within 5 to 6 weeks, 186 of 242 patients (77%) received ECV. The main reason for postponing an ECV was an inadequate international normalised ratio (INR); other reasons included spontaneous sinus rhythm and switch to rate control. A total of 23 of the 147 patients (16%) managed by the research physician were postponed due to an inadequate INR at admission versus 4 out of 98 patients (4%) managed by NPs (p = 0.005) Conclusion An inadequate INR is the main reason for postponing an ECV. Management of ECV by NPs is safe and leads to less postponing on admission.

The chance that the treatment of atrial fibrillation (AF) is successful depends on the duration of the arrhythmia. The low efficacy of cardioversion therapy after long-term AF can be explained by the occurrence of cellular adaptation mechanisms. In this article we describe ion-channel protein remodelling and structural changes in the atria of patients with persistent and paroxysmal AF and its relation with electrical remodelling.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterised by rapid and irregular contraction of the atrium. The risk of AF increases with age and AF increases the risk of various heart disorders, stroke and mortality. AF can occur in a sporadic or familial form. The underlying mechanism leading to AF is not well known but genetic analysis can increase our insight into the molecular pathways in AF. Detailed information on the molecular mechanisms of a disorder increase options for diagnosis and treatment. Recently, a gain-of-function mutation in exon of the KCNQ1 gene located on chromosome 11 was identified in a large Chinese AF family. KCNQ1 associates with KCNE1 or KCNE2 (both located on chromosome 21) to form cardiac potassium channels. Subsequent analysis of Chinese families showed a KCNE2 mutation in two families. Other genetic studies show linkage to chromosome 6 and 10, indicating genetic heterogeneity. A number of studies have shown that altered expression of the atrial connexin40 protein is a risk factor for AF. Connexin genes encode gap-junction proteins that are important in cardiac conduction and for normal wave propagation.In this study we analysed the role of KCNQ1, KCNE1 coding region and Cx40 promoter region in six Dutch AF families by sequence analysis.No mutations were found in these genes. The absence of mutations indicates genetic heterogeneity in familial AF; however, further research is needed. Candidate genes are being sequenced, linkage analysis in a large family will be performed and additional AF families will be collected.

Las declaraciones de conflicto de intereses de los expertos participantes en el desarrollo de esta guía están disponibles en la página web de la esc: http://www.escardio.org/guidelines.

Introduction: Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV), The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV. Methods and Results: Ninety-seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given, Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF, Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively. Conclusion: Stand-alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome.

Aims To examine whether the presence, or development, of atrial fibrillation in patients with advanced chronic heart failure, is associated with a poorer prognosis, compared to patients with sinus rhythm and chronic heart failure. Methods and Results We examined 409 patients with moderate to severe chronic heart failure, and compared patients with sinus rhythm (n=325) to those with atrial fibrillation (n=84). At baseline, the two groups were similar regarding most indices of severity of chronic heart failure, such as left ventricular ejection fraction (0·23) and New York Heart Association (NYHA) functional class, while they were different for age (70 years for atrial fibrillation vs 67 years for sinus rhythm patients), aetiology of chronic heart failure, blood pressure, concomitant treatment, and plasma neurohormones (all P

Focal Atrial Fibrillation and Electrical Remodeling. Although atrial fibrillation- (AF) induced changes in atrial refractoriness (atrial electrical remodeling) have been demonstrated in a number of different animal models, the clinical significance of this process is unknown. We describe a patient in whom there has been documented progression of atrial ectopy to persistent AF accompanied by evidence of atrial electrical remodeling, with reversal of remodeling following successful ablation of the focal source of AF. A second patient with focal AF, but with a "nonfocal" appearance on the ECG, is also described. These cases illustrate: (1) the possibility that a significant proportion of younger patients with idiopathic persistent AF may well ha re a focal source as the underlying abnormality; and (2) atrial electrical remodeling reverses following ablation of the underlying source.

Amiodarone is effective for long-term maintenance of sinus rhythm after electrical cardioversion of refractory atrial fibrillation or flutter. To examine its efficacy and safety for pharmacologic conversion of these arrhythmias, we studied 129 patients with refractory atrial fibrillation or flutter who had failed previous intensive conventional antiarrhythmic treatment. In anticipation of electrical cardioversion, patients were loaded with amiodarone, 600 mg/day during a 4-week period. The main outcome measure was pharmacologic conversion during this period. During the loading period, 23 patients (18%) converted to sinus rhythm. When analyzed in a multivariate model, conversion was related to desethylamiodarone plasma level (p = 0.0006), arrhythmia duration (p = 0.04), left atrial area (p = 0.02), and concomitant treatment with verapamil (p = 0.01). During ongoing atrial fibrillation after loading, the ventricular rate decreased from 100 +/- 25 to 87 +/- 27 beats/ min (p0.001). Amiodarone appeared to be safe and did not have to be discontinued because of intolerable side effects. Thus, amiodarone loading is safe and is still able to convert refractory atrial fibrillation or flutter. Conversion is related to increased desethylamiodarone plasma levels and concomitant treatment with verapamil. Because prolonged loading may increase desethylamiodarone plasma concentrations, this may enhance efficacy and obviate the need for electrical cardioversion.

OBJECTIVE: To determine the long-term outcome of serial electrical cardioversion therapy in patients with chronic atrial flutter. DESIGN: Prospective study, case series. SETTING: University hospital. PATIENTS: 50 consecutive patients with chronic (> 24 hours) atrial flutter without a previous relapse on antiarrhythmic drugs. INTERVENTIONS: Elective electrical cardioversion therapy, if necessary repeated, to obtain and keep patients in sinus rhythm. If the first cardioversion resulted in sinus rhythm, patients were not given antiarrhythmic drugs. Relapses were managed by repeated cardioversions then anti-arrhythmic drugs were used serially in a set sequence. MAIN OUTCOME MEASURE: Maintenance of sinus rhythm. RESULTS: Mean (SD) follow up was 3.5 (1.7) years. The first cardioversion was successful in 48 patients (96%). After a single shock and without antiarrhythmic drugs being used, 42% of the patients maintained sinus rhythm in the long-term. Only left atrial size was inversely related to the efficacy of one shock (P = 0.025). With serial cardioversion 90% of the patients were kept in sinus rhythm for 5 years. Univariate analysis showed that a long duration of arrhythmia and impaired cardiac function were both related to poor outcome. During follow up 3 patients died of progression of heart failure and another 5 died suddenly. None of these 5 patients was on antiarrhythmic drugs. CONCLUSIONS: Electrical cardioversion was an effective and safe method of converting chronic atrial flutter to sinus rhythm. To maintain sinus rhythm, more than half of the patients required multiple shocks and prophylactic antiarrhythmic drugs. Sudden death was relatively frequent in the study population; the limited data available from this study suggest that such deaths were caused by the underlying disease and not drug related proarrhythmia.

SummaryAtrial fibrillation (AF) is an independent risk factor for thromboembolism and stroke. Women with AF are at a higher overall risk for thromboembolic stroke when compared to men with AF. Recent evidence suggests that female sex, after adjusting for stroke risk profile and sex differences in utilisation of anticoagulation, is an independent stroke risk factor in AF. The inclusion of female sex has improved the accuracy of the CHADS2 stroke risk stratification schema (Congestive heart failure, Hypertension, Age 75 years or greater, Diabetes mellitus, and prior Stroke or TIA). The newly revised and validated schema, CHA2DS2-VASc, dichotomises age and incorporates female sex and vascular disease history. The pathophysiological mechanisms to explain this increased risk in women are not well understood. According to Virchow’s triad, thrombosis that leads to stroke in AF should arise from three co-existing phenomena: structural abnormalities, blood stasis, and a hypercoagulable state. Herein, we explore the sex differences in the biological processes that lead to thrombus formation as applied to Virchow’s Triad. The objective of this review is to describe the potential mechanisms behind the increased risk of stroke in AF associated with female sex.

In atrial flutter, chemical conversion with class I drugs is often unsuccessful, whereas class III drugs seem more promising. The different electrophysiological effects of these drugs may explain this discrepancy. To date, only experimental data show the differential effects of these drugs on conversion rate and atrial flutter cycle length. This study evaluates the effects of the class IC antiarrhythmic drug flecainide, and of dofetilide, a new class III drug, on conversion rate and flutter cycle length in patients with atrial flutter. Flecainide (11 patients) was given as an intravenous bolus of 2 mg.kg-1 in 10 min and dofetilide (10 patients) as a maximum intravenous bolus of 8 micrograms.kg-1 in 15 min. Baseline characteristics were comparable between both groups. Only one patient treated with flecainide converted to sinus rhythm. This patient showed the largest flutter cycle length increase (280 to 420 ms). By contrast, seven of the 10 patients treated with dofetilide converted to sinus rhythm. Patients treated with flecainide showed a significantly larger increase in atrial flutter cycle length at the end of the infusion compared to the dofetilide-treated patients (from 226 +/- 28 to 317 +/- 52 ms vs from 221 +/- 26 to 239 +/- 39 ms, respectively). In conclusion, dofetilide is more effective than flecainide in the conversion of atrial flutter to sinus rhythm, despite the fact that flecainide produced a more prolonged flutter cycle length. Thus, action potential prolongation in the absence of conduction slowing seems more effective in terminating human atrial flutter than depression of the excitability.

Aims To collect information on the use of the Reveal implantable loop recorder (ILR) in the patient care pathway and to investigate its effectiveness in the diagnosis of unexplained recurrent syncope in everyday clinical practice. Methods and results Prospective, multicentre, observational study conducted in 2006–2009 in 10 European countries and Israel. Eligible patients had recurrent unexplained syncope or pre-syncope. Subjects received a Reveal Plus, DX or XT. Follow up was until the first recurrence of a syncopal event leading to a diagnosis or for ≥1 year. In the course of the study, patients were evaluated by an average of three different specialists for management of their syncope and underwent a median of 13 tests (range 9–20). Significant physical trauma had been experienced in association with a syncopal episode by 36% of patients. Average follow-up time after ILR implant was 10 ± 6 months. Follow-up visit data were available for 570 subjects. The percentages of patients with recurrence of syncope were 19, 26, and 36% after 3, 6, and 12 months, respectively. Of 218 events within the study, ILR-guided diagnosis was obtained in 170 cases (78%), of which 128 (75%) were cardiac. Conclusion A large number of diagnostic tests were undertaken in patients with unexplained syncope without providing conclusive data. In contrast, the ILR revealed or contributed to establishing the mechanism of syncope in the vast majority of patients. The findings support the recommendation in current guidelines that an ILR should be implanted early rather than late in the evaluation of unexplained syncope.

International audience; AIMS: Little is known about the incidence of paroxysmal atrial tachycardias (PAT) in patients with heart failure (HF). The availability of cardiac resynchronization therapy (CRT) devices with extended diagnostics for AT enables continuous monitoring of PAT episodes. The aim of the study was to assess the incidence over time of PAT in HF patients treated with CRT. METHODS AND RESULTS: Consecutive patients in NYHA functional class III or IV despite optimal drug therapy, QRS duration > or = 130 ms, left ventricular ejection fraction < or = 35%, and left ventricular end-diastolic dimension > or = 55 mm were eligible for enrolment. Patients with permanent or persistent atrial fibrillation (AF) were not included in the study. The first follow-up examination was performed 2 weeks after implantation, to optimize atrial sensing and CRT. Subsequent follow-up examinations were carried out 15 and 28 weeks after implantation, to collect the telemetric data. A total of 173 patients (67 +/- 11 years, M 116) were enrolled. Complete arrhythmia monitoring data were available from 120 patients over a mean follow-up of 183 +/- 23 days. Atrial tachycardia episodes were detected through telemetry in 25 of 120 patients (21%) during at least one follow-up examination. Atrial tachycardia episodes were recorded in 29 and 17% (P = NS) of patients with and without previous history of AF, respectively. CONCLUSION: More than 20% of the overall HF patient population treated with CRT suffer PAT episodes. Paroxysmal atrial tachycardia may interfere with response to CRT. Therefore, telemetric data may be relevant to drive the appropriate therapy in each patient.