Screening for atrial fibrillation in high-risk individuals : a stroke preventive effort

INTRODUCTION A condition can be suitable for population screening if the disease is an important health problem, can be detected by an appropriate test and has a silent/latent stage during which treatment could be initiated in order to prevent consequences of the disease. Atrial fibrillation (AF) increases the risk of ischemic stroke 5-fold, a risk that can be reduced by at least 64% by the use of stroke-preventive, oral anticoagulant (OAC) therapy, and there are several non-invasive methods that can be used to diagnose AF. Hence it could be argued that AF is suitable for population screening. The aim of this thesis is to study the feasibility of systematic screening for AF in a high risk population and the possibility to initiate stroke-preventive anticoagulant therapy. In addition, this thesis also aims to compare different biomarkers and their association with AF, and to study if the biomarker NT-proBNP is increased in screening-detected AF. Finally, different methods for the detection of AF in a population that has already suffered an ischemic stroke or transient ischemic attack will be explored. METHODS AND RESULTS In study I all residents born in 1936/37, n=28,768, and who resided in two Swedish regions, were randomized 1:1 either to a control group or to attend a screening study. Of the 13,331 individuals who were invited, 7,173 (54%) participated. New AF was detected in 218 participants (3.0 %, 95% confidence interval (CI) 2.7-3.5) using twice daily intermittent ECG recordings for 14 days. In addition, 149 participants were known to have AF, but were not treated with oral anticoagulant therapy. Of the screened population, 5.1% (95 % CI 4.6-5.7) had untreated AF. Initiation of OAC treatment was made in 93% of participants with newly detected AF and in 3.7% (95% CI 3.3-4.2) of the screened population. Study II collected five different biomarkers: i) N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) indicative of atrial stretch, ii) high-sensitive (hs) Troponin (Tn) as a marker of myocyte damage, iii) Growth differentiation factor -15 (GDF-15), which is a marker of oxidative stress, iv) the renal biomarker cystatin C and v) the inflammatory marker hs C-reactive protein (CRP), in two Swedish cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM), n=883 and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), n=978. Risk factors for cardiovascular disease were assessed at the baseline visit. After a median follow-up of 12.6 years in ULSAM and 10 years in PIVUS, 113 (12.8%) patients developed AF in ULSAM and 148 (15.1%) in PIVUS. Unadjusted Cox regression analysis showed significant association for all biomarkers with regards to the development of AF; however, in analysis adjusted for cardiovascular risk factors and the other biomarkers, only NT-proBNP remained significantly, p < 0.001, associated with incident AF with a hazard ratio of 2.05 (1.62-2.59) in ULSAM and 1.56 (1.30-1.86) in PIVUS per 1 standard deviation increase. NT-proBNP significantly increased risk prediction, both with regards to risk factors for cardiovascular disease and the established CHARGE-AF risk score. In study III the last 815 consecutive participants from study I had a sample of NT-proBNP analysed bedside, and 71 individuals with newly detected AF had NT-proBNP taken at cardiology follow-up. Participants with newly detected AF, n=96, had significantly higher NT-proBNP (median 330 ng/L, interquartile range (IQR)121;634), compared to individuals in whom AF was not detected, n=742, median NT-proBNP 171 ng/L (IQR 95;283), p < 0.001. NT-proBNP remained significantly associated with screening-detected AF after multivariable logistic regression, p < 0.001. A cut-off of NT-proBNP 125 ng/L was shown to have a sensitivity of 75% and a negative predictive value of 92% for screening-detected AF. In study IV, 41 elderly patients (mean 76.3 +/- 5.4 years) with a prior ischemic stroke/transient ischemic attack (TIA) and no prior diagnosis of AF were included and three methods of AF detection: 24-h Holter, 30-days intermittent ECG recording, and an implantable loop recorder (ILR), were initiated in parallel after a median of 6.8 +/- 4.3 days. One patient was excluded due to a brain tumour. AF was detected in 14/40 patients, intermittent ECG detected AF in 1 patient, whereas ILR fared significantly better, p < 0.001, and detected all 14 cases. Average time to AF detection was 14.7 +/- 11.6 months. CONCLUSIONS Systematic AF screening detected a significant proportion of screened individuals with untreated atrial fibrillation. The degree of initiation of stroke-preventive therapy was high, particularly in individuals with newly detected AF. The biomarker NT-proBNP was shown in two cohort studies to be the only biomarker out of five that was significantly associated with incipient AF after adjustment for other biomarkers and clinical risk factors. Individuals with screening-detected atrial fibrillation had higher levels of NT-proBNP. In elderly patients with an ischemic stroke/TIA, parallel investigation of three methods for AF detection revealed that long-term monitoring using an implantable cardiac monitor detected significantly more AF compared to shorter time-span methods

False Alarm Reduction in Atrial Fibrillation Screening

Early detection of AF is essential and emphasizes the significance of AF screening. However, AF detection in screening ECGs, usually recorded by handheld and portable devices, is limited because of their high susceptibility to noise. In this study, the feasibility of applying a machine learning-based quality control stage, inserted between the QRS detector and AF detector blocks, is investigated with the aim to improve AF detection. A convolutional neural network was trained to classify the detections into either true or false. False detections were excluded and an updated series of QRS complexes was fed to the AF detector. The results show that the convolutional neural network-based quality control reduces the number of false alarms by 24.8% at the cost of 1.9% decrease in sensitivity compared to AF detection without any quality control

Identification of Transient Noise to Reduce False Detections in Screening for Atrial Fibrillation

Screening for atrial fibrillation (AF) with a handheld device for recording the ECG is becoming increasingly popular. The poorer signal quality of such ECGs may lead to false detection of AF, often caused by transient noise. Consequently, the need for expert review in AF screening can become extensive. A convolutional neural network (CNN) is proposed for transient noise identification in AF detection. The network is trained using the events produced by a QRS detector, classified into either true beat detections or false detections. The CNN and a low-complexity AF detector are trained and tested using the StrokeStop I database, containing 30-s ECGs from mass screening for AF in the elderly population. Performance evaluation of the CNN-based quality control using a subset of the database resulted in sensitivity, specificity, and accuracy of 96.4, 96.9, and 96.9%, respectively. By inserting the CNN before the AF detector, the false AF detections were reduced by 22.5% without any loss in sensitivity. The results show that the number of recordings calling for expert review can be significantly reduced thanks to the identification of transient noise. The reduction of false AF detections is directly linked to the time and cost spent on expert review

Gender and contemporary risk of adverse events in atrial fibrillation

Background and Aims: The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial.Methods: Population cohort study using electronic healthcare records of 16,587,749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status and comorbidities.Results: 78,852 patients were included with AF, age 40-75 years, no prior stroke and no prescription of oral anticoagulants. 28,590 (36.3%) were women and 50,262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9) with women being older and other differences in comorbidities. During total follow-up of 431,086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs men (95% CI 0.87-0.92; p&lt;0.001), and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; p&lt;0.001). This was driven by lower mortality in women (HR 0.86, 0.83-0.89; p&lt;0.001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 0.94-1.07; p=0.87), any stroke or any thromboembolism (1.02, 0.96-1.07; p=0.58), and incident vascular dementia (1.13, 0.97-1.32; p=0.11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operator curve area 0.651 vs 0.639; p&lt;0.001), and no interaction with gender (p=0.45).Conclusions: Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.  <br/

Mobile health solutions for atrial fibrillation detection and management: a systematic review

AimWe aimed to systematically review the available literature on mobile Health (mHealth) solutions, including handheld and wearable devices, implantable loop recorders (ILRs), as well as mobile platforms and support systems in atrial fibrillation (AF) detection and management.MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The electronic databases PubMed (NCBI), Embase (Ovid), and Cochrane were searched for articles published until 10 February 2021, inclusive. Given that the included studies varied widely in their design, interventions, comparators, and outcomes, no synthesis was undertaken, and we undertook a narrative review.ResultsWe found 208 studies, which were deemed potentially relevant. Of these studies included, 82, 46, and 49 studies aimed at validating handheld devices, wearables, and ILRs for AF detection and/or management, respectively, while 34 studies assessed mobile platforms/support systems. The diagnostic accuracy of mHealth solutions differs with respect to the type (handheld devices vs wearables vs ILRs) and technology used (electrocardiography vs photoplethysmography), as well as application setting (intermittent vs continuous, spot vs longitudinal assessment), and study population.ConclusionWhile the use of mHealth solutions in the detection and management of AF is becoming increasingly popular, its clinical implications merit further investigation and several barriers to widespread mHealth adaption in healthcare systems need to be overcome

ESC Working Group on e-Cardiology Position Paper: Use of Commercially Available Wearable Technology for Heart Rate and Activity Tracking in Primary and Secondary Cardiovascular Prevention

Commercially available health technologies such as smartphones and smartwatches, activity trackers and eHealth applications, commonly referred to as wearables, are increasingly available and used both in the leisure and healthcare sector for pulse and fitness/ activity tracking. The aim of the Position Paper is to identify specific barriers and knowledge gaps for the use of wearables, in particular for heart rate and activity tracking, in clinical cardiovascular healthcare to support their implementation into clinical care. The widespread use of heart rate and fitness tracking technologies provides unparalleled opportunities for capturing physiological information from large populations in the community, which has previously only been available in patient populations in the setting of healthcare provision. The availability of low-cost and high-volume physiological data from the community also provides unique challenges. While the number of patients meeting healthcare providers with data from wearables is rapidly growing, there are at present no clinical guidelines on how and when to use data from wearables in primary and secondary prevention. Technical aspects of heart rate tracking especially during activity need to be further validated. How to analyze, translate, and interpret large datasets of information into clinically applicable recommendations needs further consideration. While the current users of wearable technologies tend to be young, healthy and in the higher sociodemographic strata, wearables could potentially have a greater utility in the elderly and higher risk population. Wearables may also provide a benefit through increased health awareness, democratization of health data and patient engagement. Use of continuous monitoring may provide opportunities for detection of risk factors and disease development earlier in the causal pathway, which may provide novel applications in both prevention and clinical research. However, wearables may also have potential adverse consequences due to unintended modification of behaviour, uncertain use and interpretation of large physiological data, a possible increase in social inequality due to differential access and technological literacy, challenges with regulatory bodies and privacy issues. In the present position paper, current applications as well as specific barriers and gaps in knowledge are identified and discussed in order to support the implementation of wearable technologies from gadget-ology into clinical cardiology

2021 ISHNE/ HRS/ EHRA/ APHRS collaborative statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society.

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/ Heart Rhythm Society/ European Heart Rhythm Association/ Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored

The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: Centre and patient experiences

Aims: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck® ). We describe the characteristics, inclusion rates and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients.Methods: Three surveys exploring centre characteristics (n=25), centre experiences (n=23) and patient experiences (n=826) were completed. Self-reported patient characteristics were obtained from the app.Results: Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients (median age 64 [55-71], 62% male) agreed that the FibriCheck® app was easy to use (94%).Conclusions: Despite different health care settings and mHealth experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference

Aims Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy.Methods and results This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework.Conclusions Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.</p