Søren Zöga Diederichsen

Backgrounds and Aims: Atrial fibrillation (AF) screening may reduce adverse outcomes through early initiation of preventive treatment. However, more data are warranted to inform the yield of different screening strategies. This study aimed to evaluate how patient characteristics and screening methodologies influence screening yield. Methods: We conducted an individual participant data meta-analysis of 12 European and North American study cohorts, by using generalized linear mixed models with random intercept at study level. Results: In this meta-analysis of 34,165 participants screened for AF (age 73.4 ± 7.5 years and 53.5% female), the screening yield increased with more intensive approaches, ranging from 0.83% [95% confidence interval (CI): 0.24-2.87] in single-timepoint screening, to 5.06% [95% CI: 3.55-7.17] in intermittent (i.e. repeated single-timepoint) screening, 4.81% [95% CI: 3.79-6.08] in short-term continuous monitoring (≤30 days), and up to 30.39% [95% CI: 28.06-32.84] in long-term continuous monitoring (>30 days). Advanced age, male sex, hypertension, and heart failure (HF) were associated with detection. Significant interactions were observed between screening approach and age, sex, HF, CHADS2, and NT-proBNP. These risk factors had a stronger influence on AF detection with single-timepoint screening, compared with more intensive methods. Conclusions: In this meta-analysis, AF screening yield varied substantially by patient characteristics and screening approach. Advanced age, male sex, and HF were independently associated with greater AF detection, particularly in those having single-timepoint screening. Our findings support tailoring the screening approach to the individual target population in clinical practice. Further studies to assess clinical outcomes following screening are needed and underway.

Polygenic scores can improve atrial fibrillation risk prediction. However, limited accuracy and cross-ancestry transferability hinder clinical translation. Here, we explore several ensemble approaches to generate ancestry-optimized polygenic scores, with development in diverse participants from the All of Us Research Program, BioBank Japan, and three additional cohorts. Our ancestry-specific multi-trait approach particularly improves prediction in South-Asian (odds-ratio/standard deviation 1.5–1.8; area under curve 0.60-0.64; relative R² +71%), Admixed-American (1.5; 0.60; +34%) and African ancestry groups (1.4; 0.57; +56%). Nevertheless, performance remains highest in European and East-Asian ancestries (1.8–2.2; 0.65–0.68), where >50% of SNP-heritability is explained. Improved risk stratification is also observed at the extremes, identifying European and East-Asian ancestry individuals with risk comparable to rare TTN variants (e.g., 6–11% with >4-fold odds). Finally, our scores improve incident risk prediction alongside clinical models. Together, we show that our ancestry-tailored multi-trait polygenic scores advance atrial fibrillation risk prediction and stratification, providing an equitable foundation for implementation.

Aims: Heart failure (HF) and clinical atrial fibrillation are closely linked, but the relationship between device-detected subclinical atrial fibrillation (SCAF) and HF is unclear. We aimed to determine incidence and clinical risk factors for HF events among patients with SCAF. Methods: We included 3986 patients from the ARTESiA (Apixaban for the Reduction of Thromboembolism in Patients with Device-Detected Subclinical Atrial Fibrillation) trial. ARTESiA investigated the effect of apixaban versus aspirin for stroke prevention in patients with episodes of SCAF ≤24 hours. In this secondary analysis, we explored the number and duration of SCAF episodes at baseline as risk markers for HF hospitalization or HF-related death. SCAF progression was analysed as a time-dependent covariate and defined as the development of SCAF >24 hours or clinical atrial fibrillation. Results: Over a mean follow-up of 4.1 ± 1.7 years, SCAF progression was observed in 1244 patients (31%). Heart failure hospitalization or HF-related death occurred in 515 (13%) patients at a rate of 3.3 [95% confidence interval (CI) 3.1-3.6] per 100 person-years. A total of 172 HF-related events occurred after SCAF progression (7.2 events, 95% CI 6.2-8.3, per 100 PY). SCAF progression was an independent risk factor for HF hospitalization or HF-related death (hazard ratio 2.72, 95% CI 2.24-3.31). Conclusion: Heart failure hospitalization and HF-related death are common in patients with SCAF. Progression to longer SCAF episodes or clinical AF were associated with HF events, but episodes <24 h were not. These findings underscore the need for close surveillance of SCAF patients to detect complications and potentially improve outcomes.

Aims: Inflammation is central in atrial fibrillation (AF) pathophysiology, but the temporal association between inflammatory activity and AF remains uncertain. This study investigated the day-to-day relationship between plasma C-reactive protein (CRP) levels and AF occurrence in continuously monitored individuals. Methods and results: Post hoc analysis of the LOOP study randomizing participants with stroke risk factors to implantable loop recorder (ILR) screening (n = 1501) or usual care. ILR raw data were linked to blood samples collected within 1 day. The outcome was AF episodes lasting ≥60 min. Associations were examined using generalized and linear mixed models and as a self-controlled case series (SCCS). ILR and CRP data were available for 1065 participants combining >1.2 million days of heart rhythm monitoring (including ∼40 000 days with AF) with >7000 CRP measurements. CRP was higher during days with AF (geometric mean 8.37 [7.11–9.86] mg/L) vs. non-AF days (4.02 [3.71–4.35] mg/L). Each doubling of CRP was associated with 36% higher odds of AF (adjusted odds ratio [aOR] 1.36 [1.26–1.47]). Compared with CRP ≤3 mg/L, the odds of AF increased for CRP >10–50 and >50 mg/L (aOR 3.50 [2.18–5.60] and 5.75 [3.48–9.50], respectively). In SCCS analyses, CRP >10 mg/L was associated with higher incidence of AF compared to lower levels (incidence rate ratio 2.41 [1.53–3.80]). Conclusion: This exploratory study found a temporal and dose–response relationship between CRP levels and AF occurrence, supporting inflammation as an acute trigger and underscoring the need to evaluate inflammatory markers as potential targets in AF management. Trial Registration: ClinicalTrials.gov, identifier: NCT02036450.

Background: Subclinical atrial fibrillation (SCAF) poses an increased stroke risk, but whether oral anticoagulation for SCAF prevents stroke is unclear. We sought to investigate the treatment effect of SCAF screening according to measures of cardiac structure and function. Methods: This was an echocardiographic substudy of the LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring) study, which randomized older people at risk of stroke to usual care or an implantable loop recorder (ILR) with monitoring for SCAF and subsequent oral anticoagulation. A subset (24% of trial population) underwent echocardiography to measure left ventricular size and function, left atrial volume and strain, and valvular pathology. The primary outcome was a composite of stroke or systemic embolism. Results: The study included 1422 participants (ILR: n=1001; control: n=421; mean age: 74 years; men: 54%). During follow‐up, 354 (25%) were diagnosed with AF (ILR versus control: 30% versus 12%). During a median follow‐up of 5.5 years (interquartile range, 4.9–5.9 years), 55 (4%) developed the primary outcome (ILR versus control: 3.9% versus 3.8%). No conventional measure of cardiac structure and function modified the treatment effect from randomization. However, left atrial contraction strain significantly modified the treatment effect ( P interaction=0.003), such that a lower risk of the primary outcome was noted from ILR with lower left atrial contraction strain values (hazard ratio [HR], 0.38 [95% CI, 0.16–0.87], for participants with contraction strain<16.5%). Conclusion: In a post hoc analysis of the LOOP study, conventional echocardiographic measures did not modify the effect of SCAF screening for stroke prevention. However, a significant stroke risk reduction was observed from ILR randomization among participants with reduced left atrial contraction strain.

Atrial fibrillation (AF) is a growing unmet medical need. To reduce its impact on patients’ lives, improvements in stroke prevention therapy, treatment of concomitant conditions, and rhythm control therapy are actively developed: Innovations in anti-thrombotic agents, new anti-arrhythmic drugs (AADs), and novel interventional rhythm control therapies emerge alongside AF-reducing effects of general cardiometabolic therapies. Simple risk scores are slowly replaced by personalized AF risk estimation using quantifiable features. These developments were discussed by over 80 experts from academia and industry during the 10th Atrial Fibrillation NETwork /European Heart Rhythm Association consensus conference from 5 to 7 May 2025. The emerging consensus, described here, is multi-domain therapy combining stroke prevention, rhythm control, and therapy of concomitant cardiovascular conditions. This combines anti-coagulants, AADs, and AF ablation with old and new cardiometabolic drugs that can reduce AF risk, AF burden, and AF-related complications at scale. The paper furthermore describes quantitative traits that may enable a shift towards risk-driven therapy based on AF phenotypes. These can enable adjusted therapy strategies that are safe, accessible, and patient-centred. Applying modern data science and artificial intelligence methods to quantitative phenotypic and genetic features can further improve risk estimation and personalized therapy selection. At the same time, translational and clinical research into reversing the drivers of AF and into improved stroke prevention through new drugs and through combination therapies is needed. Together, these efforts offer pathways towards personalized, patient-centred, multi-modal, and accessible AF management that integrates rhythm control, stroke prevention, and therapy of concomitant conditions to bridge today’s practical needs with tomorrow’s therapeutic innovation.