Large variations in atrial fibrillation screening practice after ischemic stroke and transient ischemic attack in Sweden: a survey study.

BACKGROUND: Atrial fibrillation (AF) screening after ischemic stroke or transient ischemic attack (TIA) is given high priority in clinical guidelines. However, patient selection, electrocardiogram (ECG) modality and screening duration remains undecided and current recommendations vary. METHODS: The aim of this study was to investigate the clinical practice of AF screening after ischemic stroke or TIA at Swedish stroke units. In collaboration with the stakeholders of the Swedish Stroke Register (Riksstroke) a digital survey was drafted, then tested and revised by three stroke consultants. The survey consisted of 17 multiple choice/ free text questions and was sent by e-mail to the medical directors at all stroke units in Sweden. RESULTS: All 72 stroke units in Sweden responded to the survey. Most stroke units reported that ≥ 75% of ischemic stroke (69/72 stroke units) or TIA patients (67/72 stroke units), without previously known AF, were screened for AF. Inpatient telemetry ECG was the method of first-choice in 81% of the units, but 7% reported lack of access. A variety of standard monitoring durations were used for inpatient telemetry ECG. The second most common choice was Holter ECG (17%), also with considerable variations in monitoring duration. Other AF screening modalities were used as a first-choice method (handheld and patch ECG) but less frequently. CONCLUSIONS: Clinical practice for AF screening after ischemic stroke or TIA differed between Swedish stroke units, both in choice of AF screening methods as well as in monitoring durations. There is an urgent need for evidence and evidence-based recommendations in this field. TRIAL REGISTRATION: Not applicable.

Validation of a novel smartphone-based photoplethysmographic method for ambulatory heart rhythm diagnostics: the SMARTBEATS study.

AIMS: In the current guidelines, smartphone photoplethysmography (PPG) is not recommended for diagnosis of atrial fibrillation (AF), without a confirmatory electrocardiogram (ECG) recording. Previous validation studies have been performed under supervision in healthcare settings, with limited generalizability of the results. We aim to investigate the diagnostic performance of a smartphone-PPG method in a real-world setting, with ambulatory unsupervised smartphone-PPG recordings, compared with simultaneous ECG recordings and including patients with atrial flutter (AFL). METHODS AND RESULTS: Unselected patients undergoing direct current cardioversion for treatment of AF or AFL were asked to perform 1-min heart rhythm recordings post-treatment, at least twice daily for 30 days at home, using an iPhone 7 smartphone running the CORAI Heart Monitor PPG application simultaneously with a single-lead ECG recording (KardiaMobile). Photoplethysmography and ECG recordings were read independently by two experienced readers. In total, 280 patients recorded 18 005 simultaneous PPG and ECG recordings. Sufficient quality for diagnosis was seen in 96.9% (PPG) vs. 95.1% (ECG) of the recordings (P < 0.001). Manual reading of the PPG recordings, compared with manually interpreted ECG recordings, had a sensitivity, specificity, and overall accuracy of 97.7%, 99.4%, and 98.9% with AFL recordings included and 99.0%, 99.7%, and 99.5%, respectively, with AFL recordings excluded. CONCLUSION: A novel smartphone-PPG method can be used by patients unsupervised at home to achieve accurate heart rhythm diagnostics of AF and AFL with very high sensitivity and specificity. This smartphone-PPG device can be used as an independent heart rhythm diagnostic device following cardioversion, without the requirement of confirmation with ECG.

Atrial fibrillation incidence after coronary artery bypass graft surgery and percutaneous coronary intervention: the prospective AFAF cohort study.

Objectives. Atrial fibrillation is a common arrhythmia in patients with ischemic heart disease. This study aimed to determine the cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery during 30 days of follow-up. Design. This was a prospective multi-center cohort study on atrial fibrillation incidence following percutaneous coronary intervention or coronary artery bypass grafting for stable angina or non-ST-elevation acute coronary syndrome. Heart rhythm was monitored for 30 days postoperatively by in-hospital telemetry and handheld thumb ECG recordings after discharge were performed. The primary endpoint was the cumulative incidence of atrial fibrillation 30 days after the index procedure. Results. In-hospital atrial fibrillation occurred in 60/123 (49%) coronary artery bypass graft and 0/123 percutaneous coronary intervention patients (p < .001). The cumulative incidence of atrial fibrillation after 30 days was 56% (69/123) of patients undergoing coronary artery bypass grafting and 2% (3/123) of patients undergoing percutaneous coronary intervention (p < .001). CABG was a strong predictor for atrial fibrillation compared to PCI (OR 80.2, 95% CI 18.1-354.9, p < .001). Thromboembolic stroke occurred in-hospital in one coronary artery bypass graft patient unrelated to atrial fibrillation, and at 30 days in two additional patients, one in each group. There was no mortality. Conclusion. New-onset atrial fibrillation during 30 days of follow-up was rare after percutaneous coronary intervention but common after coronary artery bypass grafting. A prolonged uninterrupted heart rhythm monitoring strategy identified additional patients in both groups with new-onset atrial fibrillation after discharge.

Sensitivity and specificity of handheld one lead ECG detecting atrial fibrillation in an outpatient clinic setting.

AIMS: To validate the sensitivity and specificity of the Zenicor One handheld ECG device for detection of atrial fibrillation in an outpatient clinical setting. METHODS AND RESULTS: Patients attending outpatient clinics at Danderyd Hospital (n = 220) were examined with one lead handheld ECG immediately after standard care 12­lead ECG recording. Twelve recordings were excluded (atrial flutter or pacing) or missing. The recordings were dichotomously categorized as "atrial fibrillation" or "not atrial fibrillation" by two senior cardiologists. In cases of diverging interpretations, a third senior cardiologist had the deciding vote. Sensitivity and specificity in diagnosing atrial fibrillation was calculated with 12­lead ECG as gold standard. Sensitivity and specificity for diagnosis of atrial fibrillation with one lead handheld ECG and 12­lead ECG as gold standard was 98% and 99% respectively. CONCLUSION: In a health-care outpatient setting, Zenicor One handheld ECG had high sensitivity and specificity for detection of atrial fibrillation when compared with 12­lead ECG.

Cost-effectiveness of population screening for atrial fibrillation: the STROKESTOP study.

AIMS: Previous studies on the cost-effectiveness of screening for atrial fibrillation (AF) are based on assumptions of long-term clinical effects. The STROKESTOP study, which randomised 27 975 persons aged 75/76 years into a screening invitation group and a control group, has a median follow-up time of 6.9 years. The aim of this study was to estimate the cost-effectiveness of population-based screening for AF using clinical outcomes. METHODS AND RESULTS: The analysis is based on a Markov cohort model. The prevalence of AF, the use of oral anticoagulation, clinical event data, and all-cause mortality were taken from the STROKESTOP study. The cost for clinical events, age-specific utilities, utility decrement due to stroke, and stroke death was taken from the literature. Uncertainty in the model was considered in a probabilistic sensitivity analysis. Per 1000 individuals invited to the screening, there were 77 gained life years and 65 gained quality-adjusted life years. The incremental cost was €1.77 million lower in the screening invitation group. Gained quality-adjusted life years to a lower cost means that the screening strategy was dominant. The result from 10 000 Monte Carlo simulations showed that the AF screening strategy was cost-effective in 99.2% and cost-saving in 92.7% of the simulations. In the base-case scenario, screening of 1000 individuals resulted in 10.6 [95% confidence interval (CI): -22.5 to 1.4] fewer strokes (8.4 ischaemic and 2.2 haemorrhagic strokes), 1.0 (95% CI: -1.9 to 4.1) more cases of systemic embolism, and 2.9 (95% CI: -18.2 to 13.1) fewer bleedings associated with hospitalization. CONCLUSION: Based on the STROKESTOP study, this analysis shows that a broad AF screening strategy in an elderly population is cost-effective. Efforts should be made to increase screening participation.

Consumer-Led Screening for Atrial Fibrillation: Frontier Review of the AF-SCREEN International Collaboration.

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): a multicentre, parallel group, unmasked, randomised controlled trial.

BACKGROUND: Atrial fibrillation is a leading cause of ischaemic stroke. Early detection of atrial fibrillation can enable anticoagulant therapy to reduce ischaemic stroke and mortality. In this randomised study in an older population, we aimed to assess whether systematic screening for atrial fibrillation could reduce mortality and morbidity compared with no screening. METHODS: STROKESTOP was a multicentre, parallel group, unmasked, randomised controlled trial done in Halland and Stockholm in Sweden. All 75-76-year-olds residing in these two regions were randomly assigned (1:1) to be invited to screening for atrial fibrillation or to a control group. Participants attended local screening centres and those without a history of atrial fibrillation were asked to register intermittent electrocardiograms (ECGs) for 14 days. Treatment with oral anticoagulants was offered if atrial fibrillation was detected or untreated. All randomly assigned individuals were followed up in the intention-to-treat analysis for a minimum of 5 years for the primary combined endpoint of ischaemic or haemorrhagic stroke, systemic embolism, bleeding leading to hospitalisation, and all-cause death. This trial is registered with ClinicalTrials.gov, NCT01593553. FINDINGS: From March 1, 2012, to May 28, 2014, 28 768 individuals were assessed for eligibility and randomly assigned to be invited to screening (n=14 387) or the control group (n=14 381). 408 individuals were excluded from the intervention group and 385 were excluded from the control group due to death or migration before invitation. There was no loss to follow-up. Of those invited to screening, 7165 (51·3%) of 13 979 participated. After a median follow-up of 6·9 years (IQR 6·5-7·2), significantly fewer primary endpoint events occurred in the intervention group (4456 [31·9%] of 13 979; 5·45 events per 100 years [95% CI 5·52-5·61]) than in the control group (4616 [33·0%] of 13 996; 5·68 events per 100 years [5·52-5·85]; hazard ratio 0·96 [95% CI 0·92-1·00]; p=0·045). INTERPRETATION: Screening for atrial fibrillation showed a small net benefit compared with standard of care, indicating that screening is safe and beneficial in older populations. FUNDING: Stockholm County Council, the Swedish Heart & Lung Foundation, King Gustav V and Queen Victoria's Freemasons' Foundation, the Klebergska Foundation, the Tornspiran Foundation, the Scientific Council of Halland Region, the Southern Regional Healthcare Committee, the Swedish Stroke Fund, Carl Bennet AB, Boehringer Ingelheim, Bayer, and Bristol Myers Squibb-Pfizer.

Factors predicting participation and potential yield of screening-detected disease among non-participants in a Swedish population-based atrial fibrillation screening study.

BACKGROUND: The success of any screening program is dependent on participation. The characteristics of participants vs. non-participants have been studied and non-participants usually have a higher risk of disease. The potential yield of screening-detected disease in non-participants could be of interest to several screening programs. AIMS: This is a sub-study to STROKESTOP II, a Swedish atrial fibrillation screening study. The aim was to study factors predicting participation and to estimate the potential yield of screening-detected disease in non-participants. METHODS: Individual, anonymized data for participants and non-participants with respect to socioeconomic factors, medical history and drugs dispensed were obtained from Swedish registries. A random forest model was trained to predict propensity scores for participation. The propensity scores were used to estimate potential screening-detected disease among non-participants. RESULTS: Non-participants (n = 7086) had lower income, were more likely to have been hospitalized and had higher CHA2DS2-VASc scores compared to participants (n = 6868). The strongest factor predicting non-attendance was low income. The weighted estimates suggested that the yield of new atrial fibrillation was 2.4% in non-participants compared to 2.3% in the participants, which was not significant. CONCLUSIONS: Non-participants had higher CHA2DS2-VASc scores, indicating a higher stroke-risk and presumable benefit from attending screening, although estimated new atrial fibrillation detected was not significantly more common when compared to participants. Low income was the strongest factor for predicting non-attendance and should be a focus area when planning future screening scenarios.

Risk markers of incident atrial fibrillation in patients with coronary heart disease.

BACKGROUND: In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD. METHODS AND RESULTS: Around 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios. CONCLUSIONS: In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.

Progression and clinical manifestations in screening-detected atrial fibrillation: A follow-up of the STROKESTOP study.

BACKGROUND: There is a lack of data on atrial fibrillation (AF) progression after AF screening. HYPOTHESIS: We studied the hypothesis that progression of AF subtype after AF screening was similar to the progression noted in clinical AF cases. We also studied predictors for AF progression and AF symptoms during 5-year follow-up. METHODS: All participants from the STROKESTOP study with screening-detected AF were included in this prospective cohort study (n = 218). Deceased patients, patients with dementia and/or patients receiving institutional care were excluded (n = 31). Patients were interviewed at their visit regarding symptoms, treatment with oral anticoagulation and clinical events during follow-up and instructed to record ECG using a handheld ECG recording twice daily for two weeks. RESULTS: A total of 187 patients were invited for follow-up and 120 (64%) participated. The mean age was 81.0 ± 0.6 years and 56 (47%) of the participants were women. The mean follow-up time was 5.3 ± 0.4 years. Among the participants with 5-year follow-up data available, 18% (22/120) were diagnosed with permanent AF at study entry, compared to 49/120 (41%) after five years (p < 0.001). Among patients with paroxysmal AF at study entry, 33/98 (34%) had progressed to permanent AF after five years. Among participants approximately half remained asymptomatic, whereas 48% reported predominantly mild symptoms. None of the components of CHA2DS2-VASc were significantly predictive of AF progression. CONCLUSIONS: The progression for screening-detected AF is like that of clinically detected AF. Half of the patients with screening-detected AF report symptoms over time, and symptoms were generally mild.

Net benefit of oral anticoagulants in patients with atrial fibrillation and active cancer: a nationwide cohort study.

AIMS: To estimate the net cerebrovascular benefit of prophylactic treatment with oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and active cancer. METHODS AND RESULTS: We included all Swedish patients who had been diagnosed with AF in a hospital or in a hospital-associated outpatient unit between 1 July 2005 and 1 October 2017. Patients with active cancer (n = 22 596) and without cancer (n = 440 848) were propensity score matched for the likelihood of receiving OACs at baseline. At baseline, 38.3% of cancer patients with AF and high stroke risk according to CHA2DS2-VASc score received OACs. There was a net benefit of OACs, assessed by the composite outcome of ischaemic stroke, extracranial arterial thromboembolism, all major bleedings, and death, both among patients with active cancer [hazard ratio (HR): 0.81, confidence interval (CI): 0.78-0.85] and among patients without cancer (HR: 0.81, CI: 0.80-0.82). When limiting follow-up to 1 year to minimize the effects of possible treatment cross-over and additionally accounting for death as a competing risk in cancer patients, a net cerebrovascular benefit regarding ischaemic stroke or intracranial bleeding was observed for OACs [subhazard ratio (sHR): 0.67, CI: 0.55-0.83]. A net cerebrovascular benefit was also seen for non-vitamin K antagonist OACs over warfarin after competing risk analyses in cancer patients (sHR: 0.65, CI: 0.48-0.88). CONCLUSION: Patients with AF and active cancer benefit from OAC treatment.

Stepwise mass screening for atrial fibrillation using N-terminal B-type natriuretic peptide: the STROKESTOP II study.

AIMS: To study the prevalence of unknown atrial fibrillation (AF) in a high-risk, 75/76-year-old, population using N-terminal B-type natriuretic peptide (NT-proBNP) and handheld electrocardiogram (ECG) recordings in a stepwise screening procedure. METHODS AND RESULTS: The STROKESTOP II study is a population-based cohort study in which all 75/76-year-old in the Stockholm region (n = 28 712) were randomized 1:1 to be invited to an AF screening programme or to serve as the control group. Participants without known AF had NT-proBNP analysed and were stratified into low-risk (NT-proBNP <125 ng/L) and high-risk (NT-proBNP ≥125 ng/L) groups. The high-risk group was offered extended ECG-screening, whereas the low-risk group performed only one single-lead ECG recording. In total, 6868 individuals accepted the screening invitation of which 6315 (91.9%) did not have previously known AF. New AF was detected in 2.6% [95% confidence interval (CI) 2.2-3.0] of all participants without previous AF. In the high-risk group (n = 3766/6315, 59.6%), AF was diagnosed in 4.4% (95% CI 3.7-5.1) of the participants. Out of these, 18% had AF on their index-ECG. In the low-risk group, one participant was diagnosed with AF on index-ECG. The screening procedure resulted in an increase in known prevalence from 8.1% to 10.5% among participants. Oral anticoagulant treatment was initiated in 94.5% of the participants with newly diagnosed AF. CONCLUSION: N-terminal B-type natriuretic peptide-stratified systematic screening for AF identified 4.4% of the high-risk participants with new AF. Oral anticoagulant treatment initiation was well accepted in the group diagnosed with new AF.

Brief episodes of rapid irregular atrial activity (micro-AF) are a risk marker for atrial fibrillation: a prospective cohort study.

BACKGROUND: Short supraventricular tachycardias with atrial fibrillation (AF) characteristics are associated with an increased risk of developing AF over time. The aim of this study is to determine if presence of very short-lasting episodes of AF-like activity (micro-AF) can also be used as a marker of undiagnosed silent atrial fibrillation. METHODS: In the STROKESTOP II study, a Swedish mass screening study for AF among 75- and 76-year-olds, participants with NT-proBNP ≥125 ng/L performed intermittent ECG recordings 30 s, four times daily for 2 weeks. Participants with micro-AF (sudden onset of irregular tachycardia with episodes of ≥5 consecutive supraventricular beats and total absence of p-waves, lasting less than 30 s) were invited to undergo extended AF screening using continuous event recording for 2 weeks. A control group of individuals without micro-AF was examined using the same ECG modalities. RESULTS: Out of 3763 participants in STROKESTOP II who had elevated NT-proBNP levels and were free of AF, n = 221 (6%) had micro-AF. The majority of participants with micro-AF (n = 196) accepted further investigation with continuous ECG monitoring which showed presence of AF in 26 of them. In the control group (n = 250), continuous monitoring detected 7 new AF cases. Thus, AF was significantly more common in the micro AF group (13%) compared to the control group (3%), p < 0.001. CONCLUSIONS: Presence of short-lasting episodes of AF-like activity (micro-AF) indicates increased likelihood for undetected AF. Continuous screening therefore seems recommendable if a finding of AF would change clinical management. TRAIL REGISTRATION: ClinicalTrials.gov, identifier: NCT02743416, registered April 19, 2016.

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

A prospective 5-year follow-up after population-based systematic screening for atrial fibrillation.

Aims: Thrombo-embolic stroke risk in atrial fibrillation (AF) is significantly reduced with oral anticoagulant (OAC) treatment. Atrial fibrillation is often asymptomatic (silent) and therefore undiagnosed. The long-term course of silent AF as well as OAC treatment adherence after AF screening is not known. We aim at studying long-term adherence to OAC treatment, AF symptoms, and stroke incidence on population level after systematic AF screening. Methods and results: All inhabitants in a Swedish municipality who were born in 1934 and 1935 (n = 1335) were invited to participate in an AF screening trial between 2010 and 2012. Participants with a previously known or screening-detected AF were invited to a 5-year follow-up. Time trends of ischaemic stroke incidence were compared for population groups residing in the intervention municipality and in a surrounding control area where no AF screening trial was carried out. After the screening procedure, 103 of 121 participants (85%) with AF were treated with OAC. At the follow-up examination, 94 of 106 living patients (88%) were still on OAC treatment. Among the 23 long-term surviving patients who were diagnosed with paroxysmal AF during screening, 6 had developed permanent silent AF. The incidence of ischaemic stroke between ages 76-80 years declined significantly after the AF screening trial in the intervention area (P = 0.003) but not in the control area. Conclusion: Adherence to OAC treatment 5 years after AF screening was high. Silent AF has a natural course similar to symptomatic AF. The observed incidences of ischaemic stroke suggest a beneficial population-level effect of systematic AF screening.

Stepwise mass screening for atrial fibrillation using N-terminal pro b-type natriuretic peptide: the STROKESTOP II study design.

AIM: Atrial fibrillation (AF) is the most prevalent clinical arrhythmia and a major risk factor for ischaemic stroke. Treatment with oral anticoagulants (OACs) reduces the risk of stroke by two thirds in AF patients with risk factors. Due to its often paroxysmal and asymptomatic presentation, AF is sometimes challenging to diagnose. So far, AF screening studies have applied opportunistic or systematic screening, most often using a single 12-lead electrocardiogram (ECG) recording or ambulatory ECG. We hypothesise that the biomarker N-terminal pro b-type natriuretic peptide (NT-proBNP) is a valuable adjunct in population based AF screening. METHODS: We are conducting a randomized population-based study on AF screening using ambulatory ECG recording where the decision to use prolonged intermittent ECG recording is directed by NT-proBNP levels, the STROKESTOP II trial. The entire population of inhabitants 75 or 76 years of age (n = 28 712) in the capital region of Sweden will be randomized 1:1 to intervention or control group. In the intervention group NT-proBNP will be analysed in all without previously known AF. Those with NT-proBNP ≤ 125 pg/L will make a single one lead ECG recording, participants with NTproBNP ≥ 125 np/L will be instructed to record ECG for 30 s at least twice daily for 2 weeks with a handheld ambulatory ECG recorder. Participants with newly diagnosed or undertreated AF will be referred to a cardiologist and offered OAC treatment. Primary endpoint is incidence of stroke or systemic embolus, during a 5 year follow-up period in the control group vs the group invited to screening.

Safe automatic one-lead electrocardiogram analysis in screening for atrial fibrillation.

AIMS: Screening for atrial fibrillation (AF) using intermittent electrocardiogram (ECG) recordings can identify individuals at risk of AF-related morbidity in particular stroke. We aimed to validate the performance of an AF screening algorithm compared with manual ECG analysis by specially trained nurses and physicians (gold standard) in 30 s intermittent one-lead ECG recordings. METHODS AND RESULTS: The STROKESTOP study is a mass-screening study for AF using intermittent ECG recordings. All individuals in the study without known AF registered a 30-s ECG recording in Lead I two times daily for 2 weeks, and all ECGs were manually interpreted. A computerized algorithm was used to analyse 80 149 ECG recordings in 3209 individuals. The computerized algorithm annotated 87.1% (n = 69 789) of the recordings as sinus rhythm/minor rhythm disturbances. The manual interpretation (gold standard) was that 69 758 ECGs were normal, making the negative predictive value of the algorithm 99.9%. The number of ECGs requiring manual interpretation in order to find one pathological ECG was reduced from 288 to 35. Atrial fibrillation was diagnosed in 84 patients by manual interpretation, in all of whom the algorithm indicated pathology. On an ECG level, 278 ECGs were manually interpreted as AF, and of these the algorithm annotated 272 ECGs as pathological (sensitivity 97.8%). CONCLUSION: Automatic ECG screening using a computerized algorithm safely identifies normal ECGs in Lead I and reduces the need for manual evaluation of individual ECGs with >85% with 100% sensitivity on an individual basis.

Designing an optimal screening program for unknown atrial fibrillation: a cost-effectiveness analysis.

AIMS: The primary objective of this study was to use computer simulations to suggest an optimal age for initiation of screening for unknown atrial fibrillation and to evaluate if repeated screening will add value. METHODS AND RESULTS: In the absence of relevant clinical studies, this analysis was based on a simulation model. More than two billion different designs of screening programs for unknown atrial fibrillation were simulated and analysed. Data from the published scientific literature and registries were used to construct the model and estimate lifelong effects and costs. Costs and effects generated by 2 147 483 648 different screening designs were calculated and compared. Program designs that implied worse clinical outcome and were less cost-effective compared to other programs were excluded from the analysis. Seven program designs were identified, and considered to be cost effective depending on what the health-care decision makers are ready to pay for gaining a quality-adjusted life-year (QALY). Screening at the age of 75 implied the lowest cost per gained QALY (€4 800/QALY). CONCLUSION: In conclusion, examining the results of more than two billion simulated screening program designs for unknown atrial fibrillation, seven designs were deemed cost-effective depending on how much we are prepared to pay for gaining QALYs. Our results showed that repeated screening for atrial fibrillation implied additional health benefits to a reasonable cost compared to one-off screening.