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.

Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.

Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.

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.

Atrial Fibrillation, Oral Anticoagulants, and Concomitant Active Cancer: Benefits and Risks.

Aim To determine to what extent active cancer influences the benefit-risk relationship among patients with atrial fibrillation receiving oral anticoagulants for stroke prevention. Methods In this cohort study of all patients with atrial fibrillation in the Swedish Patient register during 2006 to 2017, 8,228 patients with active cancer and 323,394 without cancer were followed up to 1 year after initiation of oral anticoagulants. Cox regression models, adjusting for confounders and the competing risk of death, were used to assess risk of cerebrovascular and bleeding events. Results Among patients treated with oral anticoagulants, the risk for cerebrovascular events did not differ between cancer patients and noncancer patients (subhazard ratio [sHR]: 1.12, 95% confidence interval [CI]: 0.98-1.29). Cancer patients had a higher risk for bleedings (sHR: 1.69, CI: 1.56-1.82), but not for fatal bleedings (sHR: 1.17, CI: 0.80-1.70). Use of nonvitamin K oral anticoagulants was associated with lower risk of both cerebrovascular events and bleedings compared with warfarin. Conclusion Patients with atrial fibrillation and active cancer appear to have similar net cerebrovascular benefit of oral anticoagulant treatment to patients without cancer, despite an increased risk of nonfatal bleedings. Use of nonvitamin K oral anticoagulants was associated with lower risk of all studied outcomes.

Performance of pulse palpation compared to one-lead ECG in atrial fibrillation screening.

BACKGROUND: The 2020 European Society of Cardiology atrial fibrillation guidelines recommend opportunistic screening for atrial fibrillation by pulse taking or ECG rhythm strip in those aged over 65 years. HYPOTHESIS: We aimed to compare the diagnostic accuracy of pulse palpation to ECG rhythm strip when screening for atrial fibrillation. A secondary aim was to investigate whether participants with palpitations were more likely to be diagnosed with new atrial fibrillation. METHODS: The study population were 75/76 year old individuals that participated in the STROKESTOP II study, a Swedish screening study for atrial fibrillation. Pulse palpation of the radial pulse for 30 sec was performed by healthcare professionals and recorded as regular or irregular. Thereafter a 30-sec single-lead ECG was registered. Patients were asked also if they had a history of palpitations. RESULTS: Of the 6159 participants included in the study, 461 (7.5%) had irregular pulse. Twenty-two (4.8%) of those with irregular pulse were diagnosed with atrial fibrillation on single-lead ECG rhythm strip. Among those with regular pulse, 6 (0.1%) cases of new atrial fibrillation were found. The sensitivity of the pulse palpation test was 78.6% and positive predictive value 4.8%. The proportion of newly diagnosed atrial fibrillation was not different between those with and without history of palpitations. CONCLUSION: Pulse palpation was inferior to single-lead ECG when screening for atrial fibrillation. We therefore advocate the use of single-lead ECG rather than pulse palpation when screening for atrial fibrillation. Palpitations did not predict atrial fibrillation.

New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry.

Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.

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.

Clinical and echocardiographic characteristics of individuals aged 75/76 years old with screening-detected elevated NT-proBNP levels.

Background: High plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) indicate increased probability of congestive heart failure (CHF) and atrial fibrillation (AF) and are associated with poor prognosis. Objective: We aimed to describe the clinical and echocardiographic characteristics of a population of individuals aged 75/76 years old with NT-proBNP ≥900 ng/L without previously known CHF or AF. Methods: All individuals aged 75/76 years in the Stockholm region were randomised to a screening study for AF. Half of them were invited to screening. Of those invited, 49.5% agreed to participate. Individuals with NT-proBNP ≥900 ng/L without known CHF were invited for further clinical evaluation. Results: Among 6315 participants without AF who had NT-proBNP sampled, 102 without previously known CHF had ≥900 ng/L. Of these, 93 completed further clinical investigations. In the population that was clinically investigated, 53% were female, and the median NT-proBNP was 1200 ng/L. New AF was found in 28 (30%). The NT-proBNP value in this group was not significantly different from those where AF was not detected (median 1285 vs 1178 ng/L). Patients with newly detected AF had larger left atrial volume and higher pulmonary artery pressure than those without AF. Preserved left ventricular ejection fraction (≥50%) was found in 86% of the participants, mid-range ejection fraction (40%-49%) in 3.2% and reduced ejection fraction (<40%) in 10.8%. Thirteen patients (14%) had other serious cardiac disorders that required medical attention. Conclusion: Elderly individuals with NT-proBNP levels ≥900 ng/L constitute a population at high cardiovascular risk even in the absence of diagnosed CHF or AF, and therefore merit further investigation.

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.

Special topic section: linkages among cerebrovascular, cardiovascular, and cognitive disorders: Preventing dementia by preventing stroke: The Berlin Manifesto.

The incidence of stroke and dementia are diverging across the world, rising for those in low-and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action. © 2019 the Alzheimer's Association and the World Stroke Organisation. Published by Elsevier Inc. All rights reserved.

Preventing dementia by preventing stroke: The Berlin Manifesto.

The incidence of stroke and dementia are diverging across the world, rising for those in low- and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action.

Short lookback periods causing exaggerated stroke risk estimates in atrial fibrillation may expose patients to unnecessary anticoagulant treatment.

PURPOSE: The purpose was to investigate how different lookback periods in observational registry studies affect estimates of stroke risk in patients with atrial fibrillation and stroke risk score CHA2 DS2 -VASc 1, a level where the appreciated risk is likely to affect decisions about oral anticoagulation. METHODS: All 354 854 individuals in Sweden with a hospital diagnosis of atrial fibrillation during 2010-2016 were included. At least 13 years of observational data prior to inclusion was available for all patients. The prevalence of hypertension, heart failure, diabetes, previous thromboembolism, and vascular disease was estimated from data with different lookback periods. The incident stroke rates at CHA2 DS2 -VASc score 1 was then assessed using data with successively longer lookback periods. RESULTS: Depending on duration of lookback period, the proportion of patients with heart failure varied 2.7 times, thromboembolism 3.7 times, hypertension 4.0 times, and diabetes and vascular disease both approximately 4.5 times. During follow-up, 22 237 patients suffered an ischaemic stroke. The estimated risk without anticoagulant treatment at CHA2 DS2 -VASc score 1 was 51% higher if the scores had been calculated with the shortest lookback period than if all information had been used. CONCLUSIONS: Short lookback periods underestimate comorbidity, cause high-risk patients to be misclassified as low risk, and overestimate stroke risk at CHA2 DS2 -VASc 1. This may lead to unnecessary anticoagulant treatment of true low-risk patients. Transparency regarding lookback periods is essential for interpretation and comparison of registry studies.

Usefulness of Short-Lasting Episodes of Supraventricular Arrhythmia (Micro-Atrial Fibrillation) as a Risk Factor for Atrial Fibrillation.

According to the present European Society of Cardiology's guidelines for atrial fibrillation (AF), the definition of AF contains a 30-second time criterion, based on consensus. The aim of this cohort study is to evaluate whether very short-lasting episodes of AF, micro-AF, are risk factors for developing AF and to compare AF detection between continuous and intermittent ECG recordings applied in parallel. All participants, n = 102, were identified from the STROKESTOP study, a Swedish mass-screening study for AF. Participants were divided into 2 groups depending on results in the STROKESTOP study: a micro-AF group (with abrupt onset episodes of ≥4 consecutive supraventricular beats, irregular rate-to-rate intervals, absence of regular p waves, lasting for <30 seconds), n = 54, and a control group, n = 48. After a follow-up period participants who were clinically free of AF were invited to undergo repeat AF screening during a 2-week period, using continuous ECG recording and 30 seconds intermittent recordings simultaneously. After 2.3years of follow-up, significantly more participants in the micro-AF group had developed AF, 27 of 54 (50%), compared with the control group, 5 of 48 (10%), p < 0.001. Among the 94 participants not already diagnosed with AF who underwent AF-screening, 25 of 25 (100%) AF cases were detected with help of continuous monitoring whereas 10 of 25 (40%) AF cases were found with intermittent ECGs. In conclusion, micro-AF seems to be an important risk factor for the development of AF in an elderly population. The detection of AF was significantly higher using 2 weeks of continuous ECG monitoring compared with intermittent 30-second ECG recordings twice daily for 2 weeks.

Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter.

BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism. METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity. RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population. CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

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.

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.

N-terminal pro B-type natriuretic peptide in systematic screening for atrial fibrillation.

OBJECTIVE: Screening for atrial fibrillation (AF) in individuals aged 65 and above is recommended by the European Society of Cardiology. Increased levels of the biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has in cohort studies been associated with incident AF.The aim of this study was to assess whether NT-proBNP could be useful for AF detection in systematic screening. METHODS: The Strokestop study entailed 7173 Swedish residents aged 75/76 that were screened for AF using twice daily intermittent ECG recordings during 2 weeks. In a substudy of 886 participants, the last 815 consecutive participants and 71 individuals with newly detected AF, levels of NT-proBNP were determined. RESULTS: Participants with newly detected AF (n=96) had a median NT-proBNP of 330 ng/L (IQR 121;634). In individuals without AF (n=742), median NT-proBNP was 171 ng/L (IQR 95;283), p<0.001. The CHA2DS2-VASc parameters did not differ significantly between individuals with newly detected AF and without AF nor between newly detected AF in the NT-proBNP cohort compared with the cohort where NT-proBNP was not assessed. Using an NT-proBNP cut-off of ≥125 ng/L in a non-acute setting yielded a negative predictive value of 92%, meaning that 35% fewer participants would need to be screened when applied to systematic AF screening. Adding weight to NT-proBNP further reduced participants needed to be screened with a preserved sensitivity. CONCLUSIONS: NT-proBNP was increased in individuals with newly detected AF. Prospective studies could clarify if NT-proBNP can be used to correctly select individuals that benefit most from AF screening. CLINICAL TRIALS: ClinicalTrials.gov. Identifier: NCT01593553.

Geographic and socio-demographic differences in uptake of population-based screening for atrial fibrillation: The STROKESTOP I study.

BACKGROUND: The rationale behind screening for atrial fibrillation (AF) is to prevent ischemic stroke. Socio-demographic differences are expected to affect screening uptake. Geographic differences may provide further insights leading to targeted interventions for improved uptake. The objective of this study was to evaluate geographic and socio-demographic differences in uptake of AF screening in the population-based study STROKESTOP I. METHODS: STROKESTOP was carried out in two Swedish counties with a total population of 2.3 million inhabitants. Half of the residents aged 75-76years were randomized to the screening arm: invitation to clinical examination followed by ambulant ECG recording. Information on each invited person's residential parish (n=157) was used. On parish-level, aggregated data for the participants and non-participants, respectively, were obtained with respect to socioeconomic variables: educational level, disposable income, immigrant and marital status. Geo-maps displaying participation ratios were estimated by hierarchical Bayes methods. RESULTS: The overall participation rate was similar in men and women but lower in Stockholm, 47.6% (5665/11,903) than in Halland, 61.2% (1495/2443). Participation was clearly associated with the socioeconomic variables. Participation not taking into account socioeconomy varied more markedly across the parishes in the Stockholm county (range: 0.65-1.26) than in the Halland county (0.94-1.27). After adjustment for socioeconomic variables, a geographic variation remained in Stockholm, but not in Halland. CONCLUSION: Participation in AF screening varied according to socioeconomic conditions. Geographic variation in participation was marked in the Stockholm county, with only one screening clinic. Geo-mapping of participation yielded useful information needed to intervene for improved screening uptake.

Cost-effectiveness of mass screening for untreated atrial fibrillation using intermittent ECG recording.

AIMS: The aim of this study was to estimate the cost-effectiveness of 2 weeks of intermittent screening for asymptomatic atrial fibrillation (AF) in 75/76-year-old individuals. METHODS AND RESULTS: The cost-effectiveness analysis of screening in 75-year-old individuals was based on a lifelong decision analytic Markov model. In this model, 1000 hypothetical individuals, who matched the population of the STROKESTOP study, were simulated. The population was analysed for different parameters such as prevalence, AF status, treatment with oral anticoagulation, stroke risk, utility, and costs. In the base-case scenario, screening of 1000 individuals resulted in 263 fewer patient-years with undetected AF. This implies eight fewer strokes, 11 more life-years, and 12 more quality-adjusted life years (QALYs) per 1000 screened individuals. The screening implies an incremental cost of €50 012, resulting in a cost of €4313 per gained QALY and €6583 per avoided stroke. CONCLUSIONS: With the use of a decision analytic simulation model, it has been shown that screening for asymptomatic AF in 75/76-year-old individuals is cost-effective.