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Background: The clinical value of insertable cardiac monitoring (ICM) for detecting asymptomatic atrial fibrillation (AF) and guiding anticoagulation in patients with cryptogenic stroke remains uncertain. This study aimed to evaluate the association between ICM detected AF and recurrent stroke, mortality, and major bleeding in women.

Methods: We consecutively compared women with cryptogenic stroke who received an ICM at Akershus University Hospital (2016-2023), with a control group from Haukeland University Hospital with standard non-invasive follow-up. Participants from both hospitals had complete data in the Norwegian Stroke Registry. Primary outcomes were AF detection and recurrent stroke at 1 and 2 years; secondary outcomes included mortality, composite stroke and mortality, ischaemic cardiovascular events, oral anticoagulation initiation, and major bleeding. Multivariable logistic regression analysis was used for binary outcomes and Cox proportional hazards models for time-to-event outcomes, both adjusted for prespecified vascular risk factors.

Results: Among 475 women (mean age 73 ± 12 years; ICM n = 262), AF was detected in 36% in the ICM group versus 9% in in the control group (OR 6.9, 95% CI 3.7-13.5; p < 0.001). No significant differences were observed in recurrent stroke (HR 1.8, 95% CI 0.78-4.36; p = 0.17), mortality (HR 0.88, 95% CI 0.58-1.58; p = 0.88), or the composite outcome (HR 0.96, 95% CI 0.6-1.5; p = 0.85) with a median follow-up of 42 months (IQR 15-66). However, fixed-time analyses showed significantly lower 2-year mortality with ICM (OR 0.40, 95% CI 0.16-0.94; p = 0.036) and fewer bleeding events (OR 0.19, 95% CI 0.06-0.52; p = 0.002). Age and troponin T were consistent independent predictors of adverse outcomes.

Conclusion: ICM increased AF detection and enabled safe anticoagulation in women with acute cryptogenic stroke. Although stroke recurrence did not differ significantly, signals of lower mortality and major bleeding support prolonged monitoring to optimise secondary prevention.

Background and aims: Pulsed field ablation (PFA) is an established technology for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). However, data on long-term outcome remain scarce.

Methods: We conducted a retrospective analysis of our single-centre data of 339 patients (63% paroxysmal AF, 37% persistent AF), as well as of 55 redo procedures in patients, who underwent first PVI with a pentaspline PFA catheter.

Results: During the median follow-up (FUP) of 752 (391-1486) days, 34% patients (n=116) experienced arrhythmia recurrence after a blanking-period of 90 days, with a median time to recurrence of 218 (90-1161) days. Multivariate analysis showed electrical cardioversion at the end [HR 1.97 (95% CI 1.17-3.33), p=0.011] and AF at the beginning of the procedure [HR 1.73 (95% CI 1.04-2.88), p=0.034] being independently associated with a higher risk of arrhythmia recurrence. Additional anterior flower applications were protective in the univariate (p=0.025) analysis. Atrial tachycardia (AT) was present in 16%/37%/0%/0% after first/second/third/fourth procedure. In 55 analysed redo procedures 104/221 veins (47%) were reconnected (0/1/2/3/4 reconnected veins: 9%/31%/27.3%/27.3%/5.4%). Analysis of multiple procedure outcome estimates improved long-term arrhythmia-free survival, with an overall success rate of 86% after ≥ 2 procedures.

Conclusion: PV reconnections are frequent in patients presenting for repeat ablations, especially at the anterior PV aspect. A multiple procedure approach estimates arrhythmia-free survival in 86% of patients. Procedures with additional anterior lesions at the right pulmonary veins (RPVs) could be protective for recurrences.

Aims: Missense variants in the CALM1, CALM2, and CALM3 genes cause calmodulinopathy, which is characterised by ventricular arrhythmias and sudden cardiac death. Although the three genes encode an identical protein, their individual roles and gene-specific clinical implications remain poorly understood. We aimed to determine the relative contribution from each of the genes to the total calmodulin amount and assess the consequence of missense mutations on the severity of calmodulinopathy.

Methods and results: Using data from the Genotype-Tissue Expression (GTEx) project, we show that CALM2 constituted a higher percentage of the calmodulin-coding mRNA (41.9%) compared to CALM1 (36.8%) and CALM3 (21.3%) (p < 2×10-16). Paired RNA sequencing and ribosome profiling data from the left ventricle was used to demonstrate that the translation into calmodulin protein was significantly different among CALM1 (44.8%) and CALM2 (44.2%), and CALM3 (11.0%) (p < 2×10-16). The observed-to-expected ratio for the number of missense variants in the Genome Aggregation Database (gnomAD) was 0.29 (90% CI, 0.23-0.36) in CALM3, 0.20 (90% CI, 0.15-0.27) in CALM2, and 0.11 in CALM1 (90% CI, 0.07-0.17). In the International Calmodulinopathy Registry, a different percentage of carriers experiencing cardiac events was observed among those with missense variants in CALM1 (46/52, 89%), CALM2 (37/53, 70%), and CALM3 (20/35, 57%) (p = 0.004).

Conclusions: Compared to CALM1 and CALM2, CALM3 is under less negative selection and missense variant carriers are less prone to cardiac events. We suggest this is partially due to CALM3 accounting for only 11% of the calmodulin protein produced in the ventricles.

Background: Data on pulsed-field ablation (PFA) for atrial fibrillation (AF) in patients with heart failure (HF) are limited.

Objective: To evaluate clinical outcomes of PFA in patients with AF and HF, stratified by HF subtype.

Methods: Consecutive patients undergoing first-time pentaspline PFA within the ATHENA registry were analyzed. Patients were stratified into three groups: no HF, HF with preserved ejection fraction (HFpEF, LVEF ≥50%), and HF with mildly reduced or reduced EF (HFmrEF/rEF, LVEF <50%). The primary endpoint was freedom from documented atrial arrhythmias >30 seconds after a 2-month blanking period. AAD use was left to physician discretion.

Results: Among 1,224 patients included (68.5% with paroxysmal AF and 31.5% with persistent AF), 176 (14.4%) had HF: 40 (3.3%) with HFpEF and 136 (11.1%) with HFmrEF/rEF. The Kaplan-Meier estimated freedom from any atrial arrhythmias at 1-year follow-up was 79.9%, with higher rate in the no-HF group (81.0%) vs the HF group (73.3%, HR=1.5, 95%CI: 1.1-2.1, p=0.0133). Considering separately paroxysmal and persistent AF form, paroxysmal AF patients with no sign of HF showed significantly higher freedom from atrial arrhythmias (82.2%) than patients with HF (68.6%, 2.0, 1.3-3.1, p=0.0028), while no differences were found in patients with persistent AF (77.9% vs 76.4%, 1.1, 0.7-1.7, p=0.7065).

Conclusion: PFA with the pentaspline catheter appears to be an effective treatment for AF in patients with HF. Freedom from AF and atrial arrhythmias post-PFA was highest in patients with paroxysmal AF and no history of HF, with no significant differences observed in persistent AF patients.

Background and aims: It is essential to understand the key barriers and stakeholder needs related to screening to focus efforts for designing appropriate programs. Therefore, this study aimed to synthesise the existing literature to understand the pertinent concepts and requirements from key stakeholders regarding implementation of atrial fibrillation (AF) screening.

Methods: Database searches were run in MEDLINE via Ovid, Embase via Ovid, CINAHL via Ebsco, PsycInfo via Ebsco, Scopus, and Web of Science Core Collection using specified keywords; supplemented by Google and grey literature searches. Original research papers were included if they contained stakeholder views on implementation of AF screening. A critical interpretive synthesis of data was performed.

Results: From 13,332 titles/abstracts, 105 full texts were reviewed, and 34 papers included (16 qualitative; 8 surveys; 10 mixed-methods). Significant evidence gaps were identified related to systematic and population-wide screening programs; and views from system-level stakeholders/key decision-makers. The key themes were: 1) VALUE, BENEFITS AND RISKS OF SCREENING: Stakeholders were cautiously optimistic, liked enhanced practice roles; and positive about health benefits. Concerns raised about potential risks/harms (e.g. anticoagulation), worry for patients, and increased burden for the practice/healthcare system. 2) PERSPECTIVES ON APPROPRIATE MODELS: Systematic screening not supported by evidence; risk-based approaches suggested; handheld ECG perceived as quick and easy-to-use; concerns raised over direct-to-consumer devices. 3) FACTORS IMPACTING IMPLEMENTATION WITHIN HEALTHCARE SETTINGS: Time constraints, impact on workflow, remuneration/reimbursement, and data systems and data security problems were the most common barriers. 4) SYSTEMIC BARRIERS: These included the need for evidence of benefit; clear guidelines and pathways; adequate remuneration/reimbursement; importance of inter-agency collaboration; software; and access and inclusivity for all patients.

Conclusion: AF screening is acceptable however definitive evidence regarding need and harms is required. Implementation will require collaboration across healthcare sectors; local solutions; equitable access; remuneration/reimbursement; defined responsibilities and clear pathways; consideration of integration of complex systems; and data security solutions. Given the central importance of system level barriers, more research is needed on the perspectives and needs of system-level stakeholders, key decision-makers and consumer groups. Additionally, further research is required to identify strategies for how to address barriers in specific health care jurisdictions.

Background and aims: Hyperthyroidism is a risk factor for atrial fibrillation (AF), and N6-methyladenosine (m6A) RNA methylation is crucial in cardiovascular regulation. However, the role of Fto-mediated m6A demethylation in hyperthyroidism-related AF remains unclear.

Methods: We consecutively recruited 232 AF patients undergoing ablation, stratified into age-, gender-, and comorbidity-matched cohorts, 116 with manifest hyperthyroidism and 116 without manifest hyperthyroidism. Assessments included thyroid profiles, echocardiography, low-voltage area (LVA) mapping, and 1-year recurrence. T4-treated mice with cardiomyocyte-specific Fto knockout or AAV9-mediated Fto overexpression were used. Electrophysiological and structural properties were assessed via electrical mapping and echocardiography. Mechanisms were further investigated in neonatal rat atrial myocytes (NRAMs).

Results: The hyperthyroid group showed higher 1-year recurrence (19.8% vs. 5.2%, P < 0.001) and larger LVA (27.81% vs. 20.25%, P < 0.001). Hyperthyroidism independently predicted LVA expansion (OR = 2.868, P < 0.001). In mice, Fto upregulation increased atrial fibrosis and AF susceptibility, while its deletion attenuated T4-induced atrial fibrosis and AF. Wild-type Fto overexpression promoted AF via m6A-dependent enhancement of lysyl oxidase (Lox) expression. Studies in NRAMs demonstrated that Fto enhanced the transcription and translation of  Lox  by reducing m6A methylation on Lox  mRNA. Lox inhibition with BAPN suppressed fibrosis and AF inducibility.

Conclusions: Hyperthyroidism promoted atrial arrhythmogenicity through Fto-mediated m6A demethylation of Lox, increasing Lox expression and atrial fibrosis. Targeting Fto-m6A-Lox may offer a novel therapy for hyperthyroidism-associated AF.

Aims: Occupational exposure to ionizing radiation in electrophysiology may significantly affect the careers of women of reproductive age. The aim of the STOOP registry was to quantify the estimated yearly occupational radiation exposure of female electrophysiologists of reproductive age performing consecutive radiofrequency catheter ablation (RFCA) for supraventricular tachycardia (SVT) adopting a fluoroscopy-minimization strategy.

Methods: Twelve European centres participated. All procedures were performed with a fluoroscopy-minimization strategy, guided by 3D mapping systems and following the As Low As Reasonably Achievable (ALARA) principles.

Results: A total of 710 RFCA procedures were performed by 32 operators (mean age38 ± 7 years). Mean procedure time was 80 ± 35 min, with a mean fluoroscopy time of 51 ± 153 s. The mean operator annual dose-area product (DAP) was 46.7 ± 79.5 Gy·cm², corresponding to an estimated mean annual effective dose of 9.34 ± 15.9 µSv. In no case did the yearly effective dose reach the 1 mSv occupational limit for pregnancy. The mean DAP did not differ among operators and was unaffected by operator experience or annual procedure volume.

Conclusion: Performing SVT ablation with a fluoroscopy-minimization strategy results in operator radiation exposure far below the 1 mSv foetal dose constraint applicable once pregnancy is declared, irrespective of operator experience or case volume. These findings support the safety of continuing electrophysiology activity for women of reproductive age under modern fluoroscopy-free workflows.