Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study.

BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.

Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using a smartphone PPG app: the Dutch-GERAF study.

BACKGROUND: Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). METHODS: This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65 years and the ability to perform at least three PPG recordings within 6 months. Exclusion criteria are the presence of a cardiac implantable device, advanced dementia or a severe tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after a positive PPG recording, a confirmatory electrocardiogram is performed. Patients undergo a comprehensive geriatric assessment and a frailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6 months, 12 months and 3 years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality. DISCUSSION: The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population. TRIAL REGISTRATION: NCT05337202.

Interventions to prevent postoperative atrial fibrillation in Dutch cardiothoracic centres: a survey study.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is a common phenomenon following cardiac surgery. In this study, we assessed current preventive strategies used by Dutch cardiothoracic centres, identified common views on this matter and related these to international guidelines. METHODS: We developed an online questionnaire and sent it to all cardiothoracic surgery centres in the Netherlands. The questionnaire concerned the management of POAF and the use of pharmaceutical therapies (beta-blockers and calcium antagonists) and non-pharmaceutical methods (posterior left pericardiotomy, pericardial flushing and epicardial botulinum toxin type A injections). Usage of electrical cardioversions, anticoagulants and left atrial appendage closure were also enquired. RESULTS: Of the 15 centres, 14 (93%) responded to the survey and 13 reported a POAF incidence, ranging from 20 to 30%. Of these 14 centres, 6 prescribed preoperative AF prophylaxis to their patients, of which non-sotalol beta-blockers were prescribed most commonly (57%). Postoperative medication was administered by all centres and included non-sotalol beta-blockers (38%), sotalol (24%), digoxin (14%), calcium antagonists (13%) and amiodarone (10%). Only 2 centres used posterior left pericardiotomy or pericardial flushing as surgical manoeuvres to prevent POAF. Moreover, respondents expressed the need for guidance on anticoagulant use. CONCLUSION: Despite the use of various preventive strategies, the reported incidence of POAF was similar in Dutch cardiothoracic centres. This study highlights limited use of prophylactic amiodarone and colchicine, despite recommendations by numerous guidelines, and restricted implementation of surgical strategies to prevent POAF.

Interpretation of field and LEAP potentials recorded from cardiomyocyte monolayers.

Multielectrode arrays (MEAs) are the method of choice for electrophysiological characterization of cardiomyocyte monolayers. The field potentials recorded using an MEA are like extracellular electrograms recorded from the myocardium using conventional electrodes. Nevertheless, different criteria are used to interpret field potentials and extracellular electrograms, which hamper correct interpretation and translation to the patient. To validate the criteria for interpretation of field potentials, we used neonatal rat cardiomyocytes to generate monolayers. We recorded field potentials using an MEA and simultaneously recorded action potentials using sharp microelectrodes. In parallel, we recreated our experimental setting in silico and performed simulations. We show that the amplitude of the local RS complex of a field potential correlated with conduction velocity in silico but not in vitro. The peak time of the T wave in field potentials exhibited a strong correlation with APD90 while the steepest upslope correlated well with APD50. However, this relationship only holds when the T wave displayed a biphasic pattern. Next, we simulated local extracellular action potentials (LEAPs). The shape of the LEAP differed markedly from the shape of the local action potential, but the final duration of the LEAP coincided with APD90. Criteria for interpretation of extracellular electrograms should be applied to field potentials. This will provide a strong basis for the analysis of heterogeneity in conduction velocity and repolarization in cultured monolayers of cardiomyocytes. Finally, a LEAP is not a recording of the local action potential but is generated by intracellular current provided by neighboring cardiomyocytes and is superior to field potential duration in estimating APD90.NEW & NOTEWORTHY We present a physiological basis for the interpretation of multielectrode array-derived, extracellular, electrical signals.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

The Use of Oral Anticoagulation Is Not Independently Associated with Mortality in Frail Older Patients with Repeated Falls.

BACKGROUND: Particularly in frail patients, anticoagulation may be underused because of the fear of bleeding. OBJECTIVE: To determine whether the use of antithrombotic medication is an independent risk factor for mortality in frail elderly with repeated falls. METHODS: All patients aged 65 years or older at the Fall and Syncope Clinic were eligible. Frailty was calculated with a Frailty Index (FI) based on the accumulation of deficits model. Risks were calculated with a cox regression analysis, adjusted for age, sex, and Frailty Index. RESULTS: 663 patients were included in this analysis. The median age was 80 years, 438 were women (66%), 73% had polypharmacy, and 380 patients (57%) had cognitive impairment. The mean FI was 0.23 (sd 0.09), 182 patients were moderately frail (27.5%), and 259 (39.1%) were severely frail. A total of 140 (21%) used oral anticoagulation and 223 (34%) used antiplatelet agents. A total of 196 patients (29.6%) died during follow-up. In the adjusted cox regression model, the use of neither antiplatelets nor anticoagulation was associated with mortality. A strong association was found with frailty (HR 74.0, 95% CI 13.1-417.3) and a weak association with age (HR 1.05, 95% CI 1.03-1.08). A lower risk of mortality was seen in women (HR 0.5, 95% CI 0.3-0.6). CONCLUSIONS: In this cohort of frail older patients, there was no independent association between the use of antithrombotic medication and mortality. A strong association with mortality was found with frailty, a weak association was found with age, and a lower mortality risk was found in women. Our data indicate that the fear of bleeding or increased mortality in frail patients with an indication for oral anticoagulation may be unjustified.

Does atrial fibrillation affect prognosis in hospitalised COVID-19 patients? A multicentre historical cohort study in the Netherlands.

OBJECTIVES: The aim of this multicentre COVID-PREDICT study (a nationwide observational cohort study that aims to better understand clinical course of COVID-19 and to predict which COVID-19 patients should receive which treatment and which type of care) was to determine the association between atrial fibrillation (AF) and mortality, intensive care unit (ICU) admission, complications and discharge destination in hospitalised COVID-19 patients. SETTING: Data from a historical cohort study in eight hospitals (both academic and non-academic) in the Netherlands between January 2020 and July 2021 were used in this study. PARTICIPANTS: 3064 hospitalised COVID-19 patients >18 years old. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the incidence of new-onset AF during hospitalisation. Secondary outcomes were the association between new-onset AF (vs prevalent or non-AF) and mortality, ICU admissions, complications and discharge destination, performed by univariable and multivariable logistic regression analyses. RESULTS: Of the 3064 included patients (60.6% men, median age: 65 years, IQR 55-75 years), 72 (2.3%) patients had prevalent AF and 164 (5.4%) patients developed new-onset AF during hospitalisation. Compared with patients without AF, patients with new-onset AF had a higher incidence of death (adjusted OR (aOR) 1.71, 95% CI 1.17 to 2.59) an ICU admission (aOR 5.45, 95% CI 3.90 to 7.61). Mortality was non-significantly different between patients with prevalent AF and those with new-onset AF (aOR 0.97, 95% CI 0.53 to 1.76). However, new-onset AF was associated with a higher incidence of ICU admission and complications compared with prevalent AF (OR 6.34, 95% CI 2.95 to 13.63, OR 3.04, 95% CI 1.67 to 5.55, respectively). CONCLUSION: New-onset AF was associated with an increased incidence of death, ICU admission, complications and a lower chance to be discharged home. These effects were far less pronounced in patients with prevalent AF. Therefore, new-onset AF seems to represent a marker of disease severity, rather than a cause of adverse outcomes.

MicroRNAs in atrial fibrillation target genes in structural remodelling.

We aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA-mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.

Prevalence and Predictors of Nonadherence to Direct Oral Anticoagulant Treatment in Patients with Atrial Fibrillation.

Background For most patients with newly diagnosed atrial fibrillation (AF), direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists. However, there is concern that the lack of monitoring may impair therapy adherence and therefore the anticoagulant effect. Objective To assess 1-year DOAC nonadherence in patients with AF and a treatment indication of at least 1 year in the Dutch health care setting, and to identify predictors of nonadherence. Methods We performed a near-nationwide historical cohort study in patients with a novel DOAC indication for AF. Data were obtained from a pharmacy database, covering 65% of all outpatient prescriptions dispensed in the Netherlands. The 1-year nonadherence was assessed by the proportion of days covered; the threshold was set at <80%. Robust Poisson regression analyses were performed to identify predictors of nonadherence. Results A total of 46,211 patients were included and the 1-year nonadherence was 6.5%. We identified male sex (risk ratio [RR] 1.23, 95% confidence interval [CI]: 1.15-1.33), younger age (age ≥60 to <70 years: RR: 1.15, 95% CI: 1.00-1.33, age <60 years: RR: 2.22, 95% CI: 1.92-2.57; reference age ≥85 years), a reduced DOAC dose (RR: 1.10, 95% CI: 1.00-1.22), a twice-daily dosing regimen (RR: 1.21, 95% CI: 1.12-1.30), and treatment with apixaban (RR: 1.16, 95% CI: 1.06-1.26, reference rivaroxaban) or dabigatran (RR: 1.25, 95% CI: 1.14-1.37) as independent predictors of 1-year nonadherence. Conclusion One-year nonadherence to DOACs was low yet relevant in patients with AF newly prescribed a DOAC. Understanding the predictors for nonadherence may help identify patients at risk.

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

Targeted ablation of epicardial ganglionated plexi during cardiac surgery with pulsed field electroporation (NEURAL AF).

BACKGROUND: Modulation of the cardiac autonomic nervous system (ANS) is a promising adjuvant therapy in the treatment of atrial fibrillation (AF). In pre-clinical models, pulsed field (PF) energy has the advantage of selectively ablating the epicardial ganglionated plexi (GP) that govern the ANS. This study aims to demonstrate the feasibility and safety of epicardial ablation of the GPs with PF during cardiac surgery with a primary efficacy outcome of prolongation of the atrial effective refractory period (AERP). METHODS: In a single-arm, prospective analysis, patients with or without a history of AF underwent epicardial GP ablation with PF during coronary artery bypass grafting (CABG). AERP was determined immediately pre- and post- GP ablation to assess cardiac ANS function. Holter monitors were performed to determine rhythm status and heart rate variability (HRV) at baseline and at 1-month post-procedure. RESULTS: Of 24 patients, 23 (96%) received the full ablation protocol. No device-related adverse effects were noted. GP ablation resulted in a 20.7 ± 19.9% extension in AERP (P < 0.001). Post-operative AF was observed in 7 (29%) patients. Holter monitoring demonstrated an increase in mean heart rate (74.0 ± 8.7 vs. 80.6 ± 12.3, P = 0.01). There were no significant changes in HRV. There were no study-related complications. CONCLUSIONS: This study demonstrates the safety and feasibility of epicardial ablation of the GP using PF to modulate the ANS during cardiac surgery. Large, randomized analyses are necessary to determine whether epicardial PF ablation can offer a meaningful impact on the cardiac ANS and reduce AF. TRIAL REGISTRATION: Clinical trial registration: NCT04775264.

Atrial epicardial adipose tissue abundantly secretes myeloperoxidase and activates atrial fibroblasts in patients with atrial fibrillation.

BACKGROUND: Epicardial adipose tissue (EAT) secretome induces fibrosis. Fibrosis, primarily extracellular matrix (ECM) produced by fibroblasts, creates a substrate for atrial fibrillation (AF). Whether the EAT secretome from patients with AF activates human atrial fibroblasts and through which components, remains unexplored. RESEARCH AIMS: (a) To investigate if the EAT secretome from patients with versus without AF increases ECM production in atrial fibroblasts. (b) To identify profibrotic proteins and processes in the EAT secretome and EAT from patients with, who will develop (future onset), and without AF. METHODS: Atrial EAT was obtainded during thoracoscopic ablation (AF, n = 20), or open-heart surgery (future onset and non-AF, n = 35). ECM gene expression of human atrial fibroblasts exposed to the EAT secretome and the proteomes of EAT secretome and EAT were assessed in patients with and without AF. Myeloperoxidase and neutrophil extracellular traps (NETs) were assessed immunohistochemically in patients with paroxysmal, persistent, future onset, and those who remain free of AF (non-AF). RESULTS: The expression of COL1A1 and FN1 in fibroblasts exposed to secretome from patients with AF was 3.7 and 4.7 times higher than in patients without AF (p < 0.05). Myeloperoxidase was the most increased protein in the EAT secretome and EAT from patients with versus without AF (FC 18.07 and 21.57, p < 0.005), as was the gene-set neutrophil degranulation. Immunohistochemically, myeloperoxidase was highest in persistent (FC 13.3, p < 0.0001) and increased in future onset AF (FC 2.4, p = 0.02) versus non-AF. Myeloperoxidase aggregated subepicardially and around fibrofatty infiltrates. NETs were increased in patients with persistent versus non-AF (p = 0.03). CONCLUSION: In AF, the EAT secretome induces ECM gene expression in atrial fibroblasts and contains abundant myeloperoxidase. EAT myeloperoxidase was increased prior to AF onset, and both myeloperoxidase and NETs were highest in persistent AF, highlighting the role of EAT neutrophils in the pathophysiology of AF.

The influence of atrial high-rate episodes on stroke and cardiovascular death: an update.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias detected by continuous rhythm monitoring by pacemakers, defibrillators, or implantable cardiac monitors. Atrial high-rate episodes occur in 10-30% of elderly patients without atrial fibrillation. However, it remains unclear whether the presence of these arrhythmias has therapeutic consequences. The presence of AHRE increases the risk of stroke compared with patients without AHRE. Oral anticoagulation would have the potential to reduce the risk of stroke in patients with AHRE but is also associated with a rate of major bleeding of ∼2%/year. The stroke rate in patients with AHRE appears to be lower than the stroke rate in patients with atrial fibrillation. Wearables like smart-watches will increase the absolute number of patients in whom atrial arrhythmias are detected. It remains unclear whether anticoagulation is effective and, equally important, safe in patients with AHRE. Two randomized clinical trials, NOAH-AFNET6 and ARTESiA, are expected to report soon. They will provide much-needed information on the efficacy and safety of oral anticoagulation in patients with AHRE.

Syncope Diagnosis at Referral to a Tertiary Syncope Unit: An in-Depth Analysis of the FAST II.

OBJECTIVE: A substantial number of patients with a transient loss of consciousness (T-LOC) are referred to a tertiary syncope unit without a diagnosis. This study investigates the final diagnoses reached in patients who, on referral, were undiagnosed or inaccurately diagnosed in secondary care. METHODS: This study is an in-depth analysis of the recently published Fainting Assessment Study II, a prospective cohort study in a tertiary syncope unit. The diagnosis at the tertiary syncope unit was established after history taking (phase 1), following autonomic function tests (phase 2), and confirming after critical follow-up of 1.5-2 years, with the adjudicated diagnosis (phase 3) by a multidisciplinary committee. Diagnoses suggested by the referring physician were considered the phase 0 diagnosis. We determined the accuracy of the phase 0 diagnosis by comparing this with the phase 3 diagnosis. RESULTS: 51% (134/264) of patients had no diagnosis upon referral (phase 0), the remaining 49% (130/264) carried a diagnosis, but 80% (104/130) considered their condition unexplained. Of the patients undiagnosed at referral, three major causes of T-LOC were revealed: reflex syncope (69%), initial orthostatic hypotension (20%) and psychogenic pseudosyncope (13%) (sum > 100% due to cases with multiple causes). Referral diagnoses were either inaccurate or incomplete in 65% of the patients and were mainly altered at tertiary care assessment to reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. A diagnosis of cardiac syncope at referral proved wrong in 17/18 patients. CONCLUSIONS: Syncope patients diagnosed or undiagnosed in primary and secondary care and referred to a syncope unit mostly suffer from reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. These causes of T-LOC do not necessarily require ancillary tests, but can be diagnosed by careful history-taking. Besides access to a network of specialized syncope units, simple interventions, such as guideline-based structured evaluation, proper risk-stratification and critical follow-up may reduce diagnostic delay and improve diagnostic accuracy for syncope.

Women Have More Recurrences of Atrial Fibrillation than Men after Thoracoscopic Ablation and Suffer More from Established Risk Factors.

INTRODUCTION: Atrial fibrillation (AF) is more prevalent in men than in women. However, women with AF are more symptomatic, have a worse quality of life, a higher stroke risk and may therefore benefit most from ablation. In this study we aim to identify the risk of recurrent AF after thoracoscopic ablation, and assess the differential impact of the risk factors for recurrence between women and men. METHOD: This is a single center cohort study, including patients undergoing thoracoscopic ablation for advanced AF between 2008 and 2019. All patients were clinically followed up for two years with quarterly 24 h Holter monitoring and ECGs for the detection of recurrent AF. Left atrial appendage (LAA) tissue was collected for collagen analysis. RESULTS: We included 571 patients, of whom 143 (25%) were women. Women were older than men (63 ± 8.3 y vs. 59 ± 8.5, p < 0.001), but had fewer cardiovascular risk factors, myocardial infarctions (1.4% vs. 6.5%, p = 0.03) and, in particular, vascular disease (7.0% vs. 16.1%, p = 0.01). Women suffered more from AF recurrence, driven by more atrial tachycardias, and sex was an independent risk factor for recurrence (HR1.41 [1.04-1.91], p = 0.028]). The presence of vascular disease was associated with an increased risk for AF recurrence in women, but not in men. In LAA histology, women had more collagen than men, as had patients with persistent compared to paroxysmal AF. CONCLUSION: Women had 15% more recurrences, driven by more atrial tachycardias, which may be explained by a more fibrotic atrial substrate. What's new? Women undergoing thoracoscopic AF ablation have a higher risk of recurrent AF, driven by more atrial tachycardias. Among patients with left atrial enlargement or persistent AF, women have worse outcomes than men. Vascular disease was a risk factor for recurrence in women, but not in men. In a histopathologic analysis of the left atrial appendage, women had more collagen than men, as had patients with persistent compared to paroxysmal AF.

14-day Holter monitoring for atrial fibrillation after ischemic stroke: The yield of guideline-recommended monitoring duration.

Introduction: Current European Stroke Organisation (ESO) guidelines recommend >48 h of continuous electrocardiographic monitoring for atrial fibrillation (AF) in all patients with ischemic stroke or transient ischemic attack (TIA) with undetermined origin. We assessed the yield of the guideline-recommended monitoring for AF, as well as of extending monitoring up to 14 days. Patients and methods: We included consecutive patients with stroke/TIA without AF in an academic hospital in The Netherlands. We reported AF incidence and number needed to screen (NNS) in the overall sample after 48 h and 14 days of Holter monitoring. Results: Among 379 patients with median age 63 years (IQR 55-73), 58% male, Holter monitoring detected 10 cases of incident AF during a median of 13 (IQR 12-14) days of monitoring. Seven AF cases were detected within the first 48 hours (incidence 1.85%, 95% CI 0.74-3.81; NNS 54), and three additional AF cases were recorded among the 362 patients with >48 h of monitoring and without AF ⩽ 48 h (incidence 0.83%, 95% CI: 0.17-2.42; NNS 121). All AF cases were detected within the first 7 days of monitoring. Our sample was subject to sampling bias favoring inclusion of participants with low AF risk. Discussion: Strengths of this work were the broad inclusion criteria as recommended by ESO guidelines, and high Holter adherence among participants. The analysis was limited by inclusion of lower-risk cases and a relatively small sample size. Conclusion: In low-risk patients with recent stroke or TIA, ESO guideline-recommended screening for AF resulted in a low AF yield, with limited additional value of monitoring up to 14 days. Our results underline the need for a personalized approach in determining a patient's optimum duration for post-stroke non-invasive ambulatory monitoring.