Background Electrical cardioversion (ECV) is widely used for restoring sinus rhythm in atrial fibrillation (AF). However, population-level trends in use of ECV in individuals with AF remain poorly characterised.Aim We examined nationwide temporal trends in ECV utilisation between 2010 and 2022 in Denmark.Methods We conducted a registry-based cohort study using Danish nationwide health data. Two cohorts were defined: (1) individuals with prevalent or newly diagnosed AF were used to quantify annual ECV volume. (2) Individuals with newly diagnosed AF were used to calculate unadjusted and age-adjusted and sex-adjusted ECV rates per 1000 person-years during the first year after diagnosis.Results The total number of ECVs per year increased almost fourfold between 2010 and 2022 (from 2204 to 8300). The 1-year age-adjusted and sex-adjusted rate of ECVs decreased from 449.5 per 1000 person-years in 2010 to 316.6 per 1000 person-years in 2021. Rates increased among individuals aged ≥75 years but declined among younger patients. When restricted to the first ECV procedure, analyses showed a twofold increase in first-time ECVs.Conclusions The increasing volume of ECVs reflects growing demand for rhythm control, while declining rates may suggest more targeted use of ECV. The findings highlight the need for resource planning and monitoring of procedural burden to support guideline implementation and equitable rhythm control delivery.

BACKGROUND AND AIMS:High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS:In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS:The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS:Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

Aim: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021. Methods and Results: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of >1 in men and >2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between Conclusion: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.

Background A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. Methods The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for “site,” type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p -value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues. Discussion This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial. Trial registration Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.

INTRODUCTION:Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (<110 beats per minute (bpm) at rest) compared with strict rate control strategy (<80 bpm at rest) on quality of life in patients with persistent or permanent atrial fibrillation. METHODS AND ANALYSIS:We plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (<110 bpm at rest) or a strict medical rate control strategy (<80 bpm at rest). The recruitment phase is planned to be 2 years with 3 years of follow-up. Recruitment is expected to start in January 2021. The primary outcome will be quality of life using the Short Form-36 (SF-36) questionnaire (physical component score). Secondary outcomes will be days alive outside hospital, symptom control using the Atrial Fibrillation Effect on Quality of Life, quality of life using the SF-36 questionnaire (mental component score) and serious adverse events. The primary assessment time point for all outcomes will be 1 year after randomisation. ETHICS AND DISSEMINATION:Ethics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER:NCT04542785.

Andersson, Charlotte; Krogager, Maria Lukács; Skals, Regitze Kuhr; Rosenbaum Appel, Emil Vincent; Theil Have, Christian; Grarup, Niels; Pedersen, Oluf; Jeppesen, Jørgen L; Pedersen, Ole Dyg; Dominguez, Helena; Dixen, Ulrik; Engstrøm, Thomas; Tønder, Niels; Roden, Dan M; Stender, Steen; Gislason, Gunnar H; Enghusen-Poulsen, Henrik; Hansen, Torben; Køber, Lars; Torp-Pedersen, Christian; Weeke, Peter Ejvin

Background The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. Methods 1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. Results Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CADGRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. Conclusions Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research.

CONTEXT Thyroid dysfunction has been associated with both increased all-cause and cardiovascular mortality, but limited data are available on mild thyroid dysfunction and cause-specific mortality. OBJECTIVE The objective of the study was to examine the risk of all-cause mortality, major adverse cardiovascular events (MACEs), and cause-specific events in subjects with overt and subclinical thyroid dysfunction. DESIGN This was a retrospective cohort study. SETTING AND PARTICIPANTS Participants in the study were subjects who underwent thyroid blood tests, without prior thyroid disease, consulting their general practitioner in 2000-2009 in Copenhagen, Denmark. MAIN OUTCOME MEASURE All-cause mortality, MACEs, and cause-specific events identified in nationwide registries were measured. RESULTS A total of 47 327 (8.4%) deaths occurred among 563 700 included subjects [mean age 48.6 (SD ± 18.2) y; 39% males]. All-cause mortality was increased in overt and subclinical hyperthyroidism [age adjusted incidence rates of 16 and 15 per 1000 person-years, respectively; incidence rate ratios (IRRs) 1.25 [95% confidence interval (CI) 1.15-1.36] and 1.23 (95% CI 1.16-1.30)] compared with euthyroid (incidence rate of 12 per 1000 person-years). Risk of MACEs was elevated in overt and subclinical hyperthyroidism [IRRs 1.16 (95% CI 1.05-1.27) and 1.09 (95% CI 1.02-1.16)] driven by heart failure [IRRs 1.14 (95% CI 0.99-1.32) and 1.20 (95% CI 1.10-1.31)]. A reduction of all-cause mortality was observed in subclinical hypothyroidism with TSH of 5-10 mIU/L [IRR 0.92 (95% CI 0.86-0.98)]. CONCLUSIONS Heart failure is the leading cause of an increased cardiovascular mortality in both overt and subclinical hyperthyroidism. Subclinical hypothyroidism with TSH 5-10 mIU/L might be associated with a lower risk of all-cause mortality.

Background and purposeAtrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long-term cardiac monitoring.MethodsPatients with CS after protocolled work-up including electrocardiography (ECG) and telemetry were included after informed consent. An implantable loop recorder (ILR) was implanted subcutaneously. PAF was defined by events of atrial arrhythmia >2min with a correlating one-lead ECG confirming the diagnosis.ResultsEighty-five patients were monitored for a mean of 569days (SD 310). PAF was documented in 18 patients (20.7%) during the study period and detected by ILR in 14 patients (16.1%). In three patients PAF was detected by other methods before or after monitoring and was undiscovered due to device sensitivity in one case. The first event of PAF was documented at a mean of 109days (SD +/- 48) after stroke onset. PAF was asymptomatic in all cases and occurred in episodes lasting predominantly between 1 and 4h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC).ConclusionsOne in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role of implantable cardiac monitors after stroke and determine the potential therapeutic benefit of OAC treatment of patients with PAF.

Objective: We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects.Methods: CTnT was measured before and 20 h after an exercise test in 157 subjects suspected of coronary artery disease (CAD).Results: CAD subjects (n = 41) had higher baseline cTnT levels compared to non-CAD subjects (n = 116), 6.39 ng/l and 3.00 ng/l, respectively, p < 0.0001, and were more likely to increase in cTnT (70.7% versus 27.6%, p < 0.0001). Net Reclassification Index for the combined variable was 19%, p = 0.02.Conclusions: Exercise-induced increase in cTnT was found to be associated with CAD and cTnT measurements improved the diagnostic evaluation.

Aims To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. Methods and Results All patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done. Conclusion New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

OBJECTIVES:To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients.DESIGN:Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level.SETTING:Primary care patients in the city of Copenhagen.SUBJECTS:Registry data for 586,460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation.MAIN OUTCOME MEASURE:Poisson regression models used to estimate risk of atrial fibrillation by thyroid function.RESULTS:Of the 586,460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562,461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12,087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation.CONCLUSION:The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.

AimsThe prognostic importance of atrial fibrillation (AF) in heart failure (HF) populations is controversial and may depend on patient selection. In the present study, we investigated the prognostic impact of AF in a large population with HF of various aetiologies.Methods and resultsWe included 2881 patients admitted to hospital with symptoms of worsening HF over a 4‐year period (2001–2004), all patients were participants in the Echocardiography and Heart Outcome Study (ECHOS). Patients were followed for up to 7 years for all‐cause mortality stratified according to heart rhythm (sinus rhythm, paroxysmal, or chronic AF) and according to the presence of ischaemic heart disease (IHD). During follow‐up, 1934 patients (67%) died. In HF patients with a history of IHD, chronic AF was associated with an increased risk of death [hazard ratio (HR) 1.44; 95% confidence interval (CI): 1.18–1.77; P < 0.001). In contrast, in patients without IHD, chronic AF was not associated with an increased mortality risk (HR 0.88; 95% CI: 0.71–1.09; P = 0.25). There was significant interaction between the aetiology of HF and the prognostic importance of chronic AF (Pinteraction = 0.003).ConclusionIn patients with HF, AF is associated with an increased risk of death only in patients with underlying IHD.