Atrial Fibrillation and Long Term ECG Monitoring of Heart Rhythm in the Tromsø Study
Phase: NA
Conditions: Atrial Fibrillation (AF), Stroke, NT-pro-BNP, Cognitive Function and Well-Being, Heart Failure
Sponsor: University Hospital of North Norway

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ATRIAL FIBRILLATION AND LONG-TERM ECG MONITORING OF HEART RHYTHM IN THE TROMSØ STUDY 
1. EXCELLENCE 
1.1. STATE OF THE ART, KNOWLEDGE NEEDS AND PROJECT OBJECTIVES 
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting more than 33 million people 
worldwide.1 AF increases the risk of ischemic stroke (IS), premature death, heart failure and cognitive 
impairment and provokes significant societal and health economic burden.2 The prevalence of AF increases 
with age, reaching from <1% in people aged < 40 years to between 10% and 17% in those aged > 80 years, 
with a higher prevalence in men than in women.3 Known risk factors for developing AF include male gender, 
age, previous heart disease, hypertension, smoking, alcohol consumption and obesity.4 Future projections 
suggest that the burden of AF may increase by >60% in 2050,5 due to ageing populations and increase in 
major AF risk factors such as obesity, inactivity, and underlying cardiovascular diseases (CVD).1 Up to one 
third of AF cases are undiagnosed due to the intermittent and often asymptomatic nature of AF.6,7  
 
Studies have shown that 20-30% of all strokes are attributed to AF and that AF confers a 2-10 fold 
increased risk of stroke dependent on age and presence of other risk factors.7,8 AF related stroke is 
particularly debilitating and potentially lethal because the size of embolism that is caused by a left atrial 
thrombus may lead to obstruction of larger cerebral arteries.9 A recent estimation from Sweden calculated 
5000 yearly strokes due to AF in Sweden with an estimated annual cost of 7,4 billion SEK.10 AF is also 
associated with an up to a 30% increased risk of developing dementia11, independent of clinical stroke 
events.12 Cognitive impairment in AF is likely related to micro-embolic events resulting in subclinical brain 
lesions (revealed by neuroimaging techniques).12 However, prior research has reported inconsistent findings 
on the association between AF and morphological changes linked to dementia detected by brain MRI, such 
as subclinical cerebral infarction, brain atrophy and white matter hyperintensities.13,14 
 
Anticoagulation treatment reduces the risk of IS by 70% in patients with AF and may potentially 
prevent premature death and cognitive impairment.7 As a large proportion of AF episodes remain 
asymptomatic15, timely diagnosis of AF remains a major challenge in clinical practice and oral anticoagulant 
therapy is often initiated only after a stroke.16 Early diagnosis and initiation of anticoagulant treatment is key 
to prevent mutilating stroke sequalae. The diagnosis of AF is made by recording the heart rhythm with an 
electrocardiogram (ECG). The ECG can be a single recording, intermittent recordings, or continuous recording 
for hours or days, and several types of devices for ECG monitoring exist. In patients with intermittent 
(paroxysmal) AF, the diagnosis is often missed by single or repeated ECG recordings, while prolonged 
continuous ECG-monitoring improves the detection rate.17 Long-term assessment of the heart rhythm is 
usually performed by a conventional Holter monitor system which requires a recording device coupled to 
electrodes on the chest.18 Although an important diagnostic improvement when implemented in the 1960ies, 
the Holter monitoring system usually features brief testing intervals (24-72 hours), is susceptible to 
Atrial fibrillation (AF) is common and increases the risk of mortality, stroke, heart failure and cognitive 
impairment. AF imposes significant burden to patients and their families, including reduced life years, 
health related quality of life, societal health and health economy. One of three AF cases are 
undiagnosed. Several methods for detection of AF exist, but most of them have major limitations and are 
associated with resource-demanding diagnostic workup in specialist health care services. This 
randomized clinical trial will evaluate whether self-screening for AF in patients with increased levels of 
NT-proBNP utilizing a novel Norwegian patch ECG sensor a) reduces AF-related morbidity and mortality 
in a well-defined cohort and b) identify factors related to individual risk. Identification of individuals at 
risk and patient-centered early diagnosis through screening can facilitate a personalized preventive 
health care approach to improve individual physical health and life quality.  

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disruptions and have high operational expenses. Because of the latter, there is a scarcity of these devices in 
numerous hospitals, which frequently results in lower utilization rates than recommended, and consequently 
extensive waiting lists.19 Other devices for AF-detection include thumb-ECG devices (TED) and implantable 
loop recorders (ILR). TEDs have been used in previous cohort studies and AF screening studies, but have 
limited heart rhythm monitoring time and consequently lower sensitivity to intermittent arrhythmias.20,21 
ILRs have also been used in a previous AF screening study5 and allow for continuous rhythm monitoring over 
years, but require surgical procedures. Watches with heart rate monitoring based on arterial pressure waves 
cannot be used for clinical diagnostics.7 Another alternative is patch ECG-devices, which in smaller studies 
have been shown to be well suited for AF screening.22-24  
 
AF fulfils most criteria for population screening; a severe and prevalent health problem that can be 
asymptomatic and for which highly effective treatment exists.25 Systematic rhythm monitoring can enable 
earlier detection of AF and initiation of anticoagulant therapy.26,27 Yet, the cost-effectiveness of AF screening 
is not settled.28 In the recently published STROKESTOP trial, a strategy with AF screening by TED twice daily 
for 2 weeks was found to reduce the composite primary outcome (stroke, systemic embolism, bleeding 
leading to hospitalization and all-cause death) by 4% and the risk of IS by 8%.21  In the Danish LOOP study, AF 
screening with ILR resulted in a three-times increase in the number of AF patients detected and 
anticoagulation initiated and a 20% reduction in the risk of stroke or systemic arterial embolism during 
follow-up, which did not reach statistical significance (HR 0.80; 95% CI 0.61–1.05; p=0.11).29 The European 
Society of Cardiology recommends screening for AF in people >75 years of age and in patients with increased 
risk of stroke, but gives no clear recommendations for method and frequency.7  
 
The CHA2DS2-VASc risk score is based on age and traditional CVD risk factors and is currently used to 
predict the risk of IS among patients with AF and guide initiation of anticoagulant treatment. The score’s 
predictive accuracy is however modest, with a C-statistic of ~0.6 for prediction of thromboembolism.30,31 N-
terminal pro-B-type natriuretic peptide (NT-proBNP) has emerged as a promising biomarker to improve risk 
prediction. Previous studies have shown that NT-proBNP is elevated in patients with AF and associated with 
the risk of stroke.32 Data from several randomized trials showed that adding NT-proBNP to the CHA2DS2-VASc 
score significantly improved the prediction of stroke in patients with AF.32-34  
The STROKESTOP II study investigates the potential of NT-proBNP as a stratification tool to improve 
efficacy of AF screening in a randomized population-based study.35 High and low risk groups were defined 
according to a cutoff of NT-proBNP ≥125ng/L. New AF was detected in 2.6% of all patients and 4.4% in the 
high risk group. A recent subgroup analysis from the randomized LOOP study36 suggests that in an older 
population with additional stroke risk factors, ILR screening is associated with a significant reduction in stroke 
risk among participants with baseline NT-proBNP above median but not among those having lower levels.36 
These results support the potential of NT-proBNP to improve the benefit of  AF screening and possibly aid in 
risk stratification for preventive treatment. However, the utility of NT-proBNP for targeting AF screening and 
prevention of AF consequences needs to be addressed in well-designed randomized trials.  
The risk of IS in patients with AF is presumed to arise from emboli generated by structural and 
functional alterations within the atria, where a pro-thrombotic milieu is established, particularly in the left 
atrial appendage.37 Consequently, a new concept of atrial cardiomyopathy has evolved, defined by complex 
structural, functional and electrophysiological changes, affecting the atria with the potential to produce 
clinically relevant manifestations.38 Several transthoracic echocardiographic parameters have emerged as 
promising biomarkers of AF. These include left arterial volume and left arterial function assessed by strain 
which are associated with AF in patients at risk39,40 and in patients with IS of undetermined source.41,42 
However, knowledge of association between echocardiographic parameters and paroxysmal AF in a general 
population is limited.  
 

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Previous studies report that AF is associated with poor health-related quality of life (HRQoL). 
However, the factors influencing HRQoL in patients with AF are not well understood. A literature review from 
201943 concluded that patients with AF had consistently lower HRQoL than healthy individuals and patients 
with other cardiovascular diseases. The most common factor associated with HRQoL in patients with AF was 
anxiety-specific. This may be related to both to the increased burden of disease associated with AF and to 
fear of complications from treatment.44,45 Effects of AF screening on HRQoL is scarcely mapped and highly 
relevant when considering the benefits of population based screening.   
 
Several knowledge gaps still exist regarding risk stratification, effectiveness, implementation and 
outcomes of screening programs for AF. Evidence on optimal screening methods in terms of accuracy, cost-
effectiveness and feasibility is lacking. Identification of individuals to target for AF screening is essential and 
the optimal approach to risk stratification for screening purposes remain unclear. Impact of AF screening on 
clinical outcomes such as stroke prevention, mortality reduction, cognitive function and quality of life is not 
fully understood and more evidence is needed to assess the long-term effects on patient outcomes, including 
potential harms associated with overdiagnosis and overtreatment. Subclinical AF refers to episodes of atrial 
arrhythmia that are asymptomatic and may only be detected through continuous monitoring. It's unclear 
whether the detection and treatment of subclinical AF lead to improved outcomes compared to clinical AF 
or if it carries a similar risk of complications such as IS.   
 
The present project is planned as a sub-study of the epidemiological population-based Tromsø Study. 
In a randomized controlled clinical trial, we plan to test the primary hypothesis that in individuals with 
elevated NT-ProBNP who are diagnosed with AF through long-term ECG monitoring, anticoagulation 
treatment according to international guidelines will reduce the incidence of stroke and cardiovascular death 
in the screening group compared to individuals who do not undergo screening (control group). The study will 
be performed within a well-defined cohort with extensive available longitudinal and cross-sectional 
information on risk factors and co-existing conditions. This setup facilitates addressing several knowledge 
gaps concerning risk stratification including associations between AF and echocardiographic parameters, 
cognitive impairment, structural changes on brain MRI, and HRQoL.  
1.2. NOVELTY AND AMBITION 
This project has the potential for providing new knowledge related to the benefit of a stepwise screening 
approach for AF according to NT-proBNP level, utilizing a novel patch monitor with continuous ECG 
monitoring and automatic artificial intelligence based (AI) ECG analysis. It can contribute to the identification  
of a population that is more likely to benefit from AF screening and address the usefulness of CHA2DS2-VASc 
and other novel biomarkers including echocardiographic parameters in the current risk factor era.  
The Tromsø Study is an internationally recognized and leading epidemiological study. Data collection 
includes questionnaires, medical interviews, blood tests and comprehensive clinical examinations with 
echocardiography, respiratory testing, cognitive testing and MRI of the brain.46,47 Many participants have 
attended previous surveys of the Tromsø Study and thus repeated measures are available for several 
individuals. This approach enables us to identify individual phenotypes with increased risk of AF and AF 
complications. Information on incident stroke, myocardial infarction, and cause-specific deaths in the 
participants are obtained through annual linkage to the national registries (the Norwegian Stroke Registry, 
the Norwegian Myocardial Infarction Registry and the Causes of Death Registry). The combination of clinical 
data including imaging data with the extensive data collection on both exposure and outcome variables and 
cross-links between the various sub-projects of the Tromsø Study provides a rich datasource for research, 
with the potential for several future PhD and postdoc-projects. 
Our project group collaborates with major projects within the national AFIB network investigating 
different aspects related to AF screening and risk stratification. Outcomes in the proposed study are 
harmonized with these projects, enabling data merging to address central knowledge gaps in larger datasets. 

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The project focuses on addressing challenges on the path towards a user-centered and sustainable 
healthcare service through collaboration and use of new technology. The project will provide new knowledge 
on the utility of novel diagnostic tools for continuous ECG monitoring analyzed with AI based algorithms with 
high sensitivity and specificity and whether this tool can simplify AF screening, and may thus impact future 
planning of AF screening.  Through the project we will identify biomarkers that would allow stratification of 
individuals with respect to screening, medical treatment, enable individual precision-based medicine, and 
ultimately reduce stroke events, with great benefit to patients and the health care system. 
 
1.3. RESEARCH QUESTIONS AND HYPOTHESES, THEORETICAL APPROACH AND METHODOLOGY  
The specific research questions which will be addressed in the present PhD project are:  
Question 1: What is the age and sex specific prevalence of paroxysmal AF (considering duration, frequency, 
heart rate and symptoms) and its association with repeated measured cardiovascular risk factors among 
Tromsø Study participants with elevated levels of NT-Pro-BNP? 
Question 2: Can the presence and burden of AF (duration, frequency, heart rate) in the general population 
with elevated level of NT-ProBNP be predicted by comprehensive echocardiographic evaluation? 
Question 3: Is atrial fibrillation associated with cognitive test performance in subjects with elevated NT-
proBNP and is this association modified by specific MRI findings?  
Question 4: Does detection of AF by continuous ECG monitoring influence health related quality of life?  
 
The project is planned as a randomized controlled screening trial within the 8th survey of the Tromsø Study 
(T8), which will be ongoing from March 2025 through 2026. All participants will be invited to complete a 
questionnaire covering lifestyle, HRQoL, risk factors, as well as simple clinical examinations such as height, 
weight, ECG, blood pressure, and blood tests. Subsets of up to 10 000 participants will be invited to a second 
visit to undergo more comprehensive examinations, including extended blood tests with NT-proBNP 
measurements, cognitive tests, MRI of the brain, and echocardiography of the heart. In the planned trial we 
aim to include 4000 individuals with NT-proBNP above median without previous known AF or ongoing 
anticoagulant treatment. Participants will be randomized 1:1 to continuous ECG monitoring using the 
Norwegian produced ECG247 sensor. ECG247 is an efficient, user-friendly and cost-effective continuous ECG 
monitor approved for both self-testing and use in health care settings.48 The sensor is connected to the 
The significance and originality of the proposal:  
We propose to perform a randomized controlled screening trial within the Tromsø 8 population-based 
cohort study, applying monitoring of heart rhythm with leading sensor technology (ECG247) in 
participants with elevated levels of NT-proBNP. We will add important data to ongoing screening trials 
by including comprehensive clinical assessments of included subjects. The overall aim of the project is to 
assess the primary hypothesis that continuous ECG-monitoring in individuals with elevated NT-pro-BNP 
and subsequent anticoagulant treatment according to current international guidelines leads to reduced 
incidence of the composite outcome ischemic stroke and cardiovascular death.  
The work performed by the PhD student for which we seek funding by this application will create new 
knowledge related to:  
1) the age and sex specific prevalence of various burdens of AF (duration, frequency, heart rate and 
symptoms) and association with repeated measured risk factors in the Tromsø Study 
2) the association between AF and echocardiographic parameters 
3) the association between AF, findings on brain MRI and results of cognitive tests 
4) participants perception of health-related quality of life before and after AF detection by 
continuous ECG monitoring 

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individual 
participants’ 
smartphone 
(Bluetooth 
technology) and has a flash 
storage if the smartphone is 
not available. Single lead 
ECG data is sent to a cloud-
based server intermittently. The 
system stores information of ECG quality and is evaluated by trained algorithms which classify arrhythmias 
based on current criteria. The stored data is easily available for the research group, and interpretation, 
validation, and reclassification if needed. The system fulfills all regulations for a screening tool, as well as 
handling of sensitive data. 
Immediate feedback based 
on an AI based algorithm for 
analysis will be provided via 
an app on the participant 
smartphone if heart rhythm 
disturbances are detected. 
ECG247 has been shown to have 
at least as good diagnostic accuracy for AF and improved user-friendliness compared to conventional Holter 
technology, enables long-term monitoring and can improve the detection of AF.48 In most cases, the 
interpretation is simple and can be performed by other professionals than cardiologists.49  
The study design enables cross-sectional and longitudinal assessments of associations between AF 
and repeated measured traditional risk factors, echocardiographic measures, findings on MRI of the brain, 
and results of cognitive tests. Long term follow-up enables comparison of the group undergoing ECG247 
monitoring to those who have not undergone ECG247 monitoring regarding clinical outcomes (after 6 years).  
Study population: A total of 4000 individuals from the general population with NT-proBNP> median fulfilling 
the inclusion criteria will be included after informed consent for study participation. 
 
Inclusion criteria: 
• 
Age ≥40 years 
• 
NT-proBNP> median level 
• 
Informed consent for participation 
 
 
Exclusion criteria: 
• 
History of AF (self-reported) 
• 
Use of anticoagulation therapy 
• 
Pacemaker/CRT device 
• 
No available smart phone 
Study procedure: Individuals with NT-proBNP > median will be identified when attending the second visit of 
the Tromsø Study. Eligible participants will be included and automatically randomized (1:1) to ECG247 
monitoring or no ECG monitoring. Participants not responding will receive two reminders. Invitation will 
continue until 4000 study participants have been included.  
Intervention: The AF screening device will be sent by post from the study centre to all participants in the 
intervention group at inclusion, free-of-charge. User guides (paper, digital and video) will be prepared 
(Norwegian and English), and an “help-desk” located at the Tromsø Study will be available for phone/video 
assistance. The monitoring of included participants will be handled by trained research nurses. All 
participants will be requested to fill in a digital questionnaire after having completed the test focusing on 
usability and adverse events. All ECG recordings will be reviewed by a group of trained and experienced study 
nurses and physicians. Cardiologists will supervise and verify pathologic ECG findings. The following variables 
will be registered: Heart rhythm (sinus rhythm, AF, atrial flutter, supraventricular tachycardias (SVT), 
Figure 1: Illustration of ECG247 practical setup, modified from www.ecg247.com 
    Figure 1: Illustration of ECG247 technical setup, modified from www.ecg247.com 

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ventricular arrhythmias, SA/AV-block, and other arrhythmias), timing, duration, heart rate of arrhythmias, 
symptoms and duration of the heart rhythm recording. All study participants will receive information about 
the test results. A new assessment of HRQoL and medication is planned 6 months post intervention. Initiation 
and adherence to anticoagulation therapy will be assessed both by questionnaires and by linkage to the 
Norwegian Prescription Register. Incidence of stroke, cardiovascular and all-cause mortality will be obtained 
from the Tromsø Study through linkage to national registries. 
Safety: In the event of clinically relevant arrhythmias, participants will be contacted as soon as possible. 
Feedback to the participants will be provided by specially trained physicians and nurses. Participants 
diagnosed with cardiac arrythmia or other cardiac abnormal findings will receive advice on follow-up with 
their general practitioner or be referred to a cardiologist depending of type of arrythmia. Anticoagulation 
therapy and other treatments will be recommended if indicated according to current guidelines. The study 
centre will assist participants who need help to book an appointment for further assessments in cases where 
this is necessary. An information video about AF will be made in collaboration with the National Association 
for Heart and Lung Diseases (LHL) to provide general information about AF and potential benefits and risks 
related to anticoagulant treatment.  
Definition of outcomes and other variables of interest: Definition of AF outcome for research question 1 
and 2: Paroxysmal AF will be defined as the presence of AF episodes ≥30 seconds. In addition, we will register 
total time in AF (AF burden), beats per minute and concomitant symptoms. Similarly, other tachycardias as 
atrial flutter (≥30 seconds), supraventricular and ventricular tachycardias (cut-offs ≥15 seconds and 5 
complexes) will also be registered. Initial evaluation will be performed by specially trained research nurses. 
All positive findings and a similar number of negative tests will be evaluated by a blinded end-point 
committee of three experts. In case of disagreement the majority will define classification of the outcome. 
Cognitive test performance outcome for research question 3: Scores on the 12-word immediate recall test, 
the digit symbol coding test and the Mini-Mental State Examination (MMS-E). AF outcomes will be as for 
question 1 and 2. “Health related quality of life (HRQoL)” outcome for research question 4: A single summary 
index value (utility score) using a predefined scoring algorithm of the HRQoL EuroQol-5 Dimension (EQ5D) 
and health anxiety using the Whiteley Index. EQ5D is a standardized instrument developed by the EuroQol 
group to measure HRQoL and consists of two parts a descriptive system comprising five dimensions (mobility, 
self-care, usual activities, pain/discomfort and anxiety/depression) and visual analog scale measured ranging 
from 0 to 100 where patients rate their perceived health status, with 0 being "worst imaginable health state" 
and 100 being "best imaginable health state." Whiteley Index consists of 14 items, and participants respond 
on a scale from "not at all" to "very much" or similar gradations. 
Relevant echocardiographic variables are atrial size (LAVI, Left Atrial volume Index) and atrial strain (LA 
reservoir strain). Relevant MRI measures are global and segmental atrophia, volume of white matter lesions, 
size, presence and number of clinical and subclinical infarcts and micro hemorrhages.  
Statistics and analyses: The associations between the primary outcome defined as AF presence(yes/no) and 
AF burden (number of hours with AF) and prespecified risk factors (traditional CVD risk factors and novel 
echocardiographic measures) will be examined using multiple regression analyses taking repeated measures 
within individuals into account by the use of generalized linear mixed effect models and linear mixed effect 
models, respectively. Linear and logistic (binary or ordinal) regression models with adjustment for relevant 
confounders will be chosen as appropriate when examining the cross-sectional associations between 
cognitive test performance and HRQoL outcomes and AF depending on the type of outcome variable 
(continuous, dichotomous or ordinal). Incidences will be reported as the number of events per 100 years at 
risk. Censoring for the composite outcome will be done at an event, death of other cause or end of follow-
up. Hazard ratios (HRs) will be obtained by Cox regression with adjustment for relevant cofactors. Suitable 
statistical software will be used for analyses and an experienced statistician will be consulted. 

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Power estimates: Power estimates are customized to test the primary hypothesis that continuous ECG-
monitoring in individuals with elevated NT-proBNP and subsequent anticoagulant treatment according to 
current international guidelines leads to reduced incidence of the composite outcome IS and cardiovascular 
death.  According to a previous study performed at Sørlandet50 with ECG247 the number needed to screen 
was 45 to detect one unrecognized case of AF in subjects at risk for stroke. When restricting screening to the 
population with NT-proBNP level > median the number needed to screen may be reduced to 3136 and even 
2335 in an older population. The 6-year risk of the composite outcome is expected to be 4% in the control 
group. Risk in the group screened where no AF is found varies from 2 to 3%. In the group screened where AF 
is found the risk is 10% (30% risk of IS during a 6-year period, reduced by 70% with oral anticoagulant 
therapy). If the 6-year risk among screened participants without AF is 2,2%, and we include 2000 participants 
in each group, there is 80% power to detect a significant difference (α=0.05) between control and 
intervention groups with estimated risk of 4.0% vs. 2.4% for the composite outcome, respectively. Based on 
the results of the Loop and StrokeStop study and the younger population in the Tromsø study, we expect to 
reduce risk of the composite outcome from 4% in the control group to 2.4% in the screening group. Compared 
to previous epidemiological studies, the planned epidemiological projects for the PhD student will have 
sufficient statistical power to explore meaningful associations.  
Data handling and storage: EUTRO is a research administrative tool that will be used for data collection and 
storage in Tromsø 8. EUTRO provides a complete overview of a study's total research material, including 
responses to questionnaires, biological material, health data, and project information. EUTRO is integrated 
within TSD (services for sensitive data located at University of Oslo) which assures and facilitates anonymized 
data handling and storage according to present regulations and research needs. All data security is taken care 
of according to the requirements from the Norwegian Data Protection Authority, and privacy is well 
maintained in the system. The system ensures compliance with the Health Research Act and GDPR 
requirements for security, handling, and administration of sensitive research data and biological material. 
Ethics: Separate applications for approval will be sent both for the Tromsø study as a whole and for the 
present study. Participants must give an informed signed consent before data collection. The study will be 
conducted in accordance with the Declaration of Helsinki. We will provide relevant feedback to all 
participants with specific recommendations including how to follow-up positive results. Participants 
diagnosed with cardiac arrythmia or other cardiac abnormal findings will receive advice on follow-up. The 
participant will either be referred to follow-up with their general practitioner or the study team will refer 
him/her to a cardiologist if indicated. Advise on starting anticoagulant treatment will comply with current 
guidelines. Appsens AS developed, manufactures and distributes the ECG247 smart heart sensor. 
Disclosures related to Jortveit being both employer and shareholder in Appsens, as well as inventor will be 
handled accordingly. No Appsens-affiliated personnel will be involved in data analyses.  
Risks and mitigation: • Patients from the Tromsø 8 study may not be willing to participate. Mitigation: A high 
percentage of patients invited to follow-up studies in previous Tromsø studies attended. Randomization will 
continue until the planned number of included participants is met • Patients do not have access to 
smartphones needed for communication between the sensor and the ECG247 platform. Mitigation: We will 
provide some smartphones for loan to participants in need in the T8 study. • Too optimistic power 
calculations if the prevalence of AF is lower than expected and the risk of the composite outcome in the 
included population is lower than expected. Mitigation: The completion of the PhD thesis is not reliant on 
collection of the composite outcome at after 6 years follow-up.  
Gender perspective: Both women and men will be invited to participate in the study. Analyses will be 
performed sex-adjusted and/or stratified by sex. The research group consists of both female and male 
researchers. In line with the project owner’s gender policy, women will be encouraged to apply for PhD 
fellowship and preferred if qualifications are otherwise equal. 

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2. IMPACT 
2.1. POTENTIAL IMPACT OF THE PROPOSED RESEARCH 
The study will provide new knowledge about risk factors, clinical findings and co-existing comorbidities in 
individuals that are associated with both increased risk of AF and clinical events. Hence, the study can 
contribute to identifying new targets and better tools for a more effective, precise and personalized 
prevention of stroke in patients with AF and provide knowledge about risk groups where long-term ECG 
monitoring would be beneficial. The project will provide novel insights into the impact of screening on HRQoL 
in participants who have AF confirmed through screening. In addition, the study will provide data on the 
prevalence of paroxysmal AF and AF burden detected by new sensor technology both being highly relevant 
outcomes and risk factors for future Tromsø-Study projects. 
In the long term, we will generate new knowledge on whether AF screening utilizing patients 
centered novel sensor technology in participants with elevated level of NT-proBNP is beneficial for patients’ 
outcomes. The study may impact future European guidelines for the prevention and treatment of AF. 
The proposal adds clinical experience and skills related in the use of sensor technology for home-
based monitoring of cardiac patients and patient-administered heart rhythm examinations without the need 
for hospital visits. Hence, more patients may gain benefit from this cost-effective and sustainable non-
invasive approach for AF detection. Reducing the need for healthcare resources, transportation, hospital 
stays away from home and work has the potential of moving health care towards more precise diagnostics 
and equal care in a sustainable manner, and also be beneficial for health-related costs and the environment. 
Using new sensor technology, some participants will through the trial be diagnosed with AF, that they 
were previously unaware of. This enables initiation of effective preventive treatment that reduces the risk of 
stroke. Successful self-screening makes AF screening possible at a population level, and consequently has a 
potential to prevent mortality and severe AF-related morbidity.  
Enhanced disease characterization can lead to more precise and personalized clinical decisions. 
Streamlining heart rhythm monitoring could reduce the need for time-intensive, repetitive manual tasks and 
patient transportation to hospitals, thereby enhancing both the efficiency and sustainability of healthcare. 
This is particularly relevant to the United Nations' Sustainable Development Goal 3 (Good Health and Well-
being; specifically target 3.4, which aims to reduce premature mortality from non-communicable diseases by 
one third by 2030 through prevention and treatment, and to promote mental health and well-being), Goal 5 
(Gender Equality), Goal 10 (Reduced Inequalities), Goal 11 (sustainable cities and human settlements). 
2.2 MEASURES OF COMMUNICATION AND EXPLOITATION 
Our goals for communication, dissemination, and engagement are to keep each stakeholder up to date and 
engaged for the recruitment, continuation, and implementation of the study outputs. Communication and 
dissemination activities will be conducted by all members of the study group. We anticipate that the findings 
will capture significant interest from both the media and patient organization. Study results are relevant to 
patients, health care providers and policy makers. Participants will be informed via letters and websites. In 
collaboration with the patient’s organization LHL we plan to make an information video about AF including 
general information and information about potential benefits and risks related to anticoagulant treatment. 
Results are communicated to researchers and healthcare professionals through scientific publications, 
conferences, regional and national meetings. Information is shared with the public via social media, podcasts, 
and news reports. Decision-makers and politicians will be informed through information meetings. The LHL 
will use own information channels (including lhl.no) to disseminate the study's results. 

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3. IMPLEMENTATION 
3.1. RESEARCER AND PROJECT GROUP 
This study is based on a broad multidisciplinary collaboration and a synergistic integration between 
researchers and clinicians is facilitated by the closely located, large multi-disciplinary research environments 
at the University Hospital of North Norway (UNN) and The Arctic university of North Norway (UiT). The main 
responsibility for planning and implementation of the study lies at the Department of Neurology, UNN and 
Institute of Clinical medicine, UiT, with significant contributions from the Institute of Community Medicine, 
UiT and the Department of cardiology, UNN. Eltoft, senior consultant at the Department of Neurology, UNN, 
associate professor at the department of Clinical Medicine, UiT, will chair the planned project and serve as 
the main supervisor.  She has completed an epidemiological PhD based on data from the Tromsø Study and 
was as trial officer part of the management of a large randomized controlled multicenter clinical trial. She is 
the local principal investigator (PI) for several clinical stroke trials ongoing at UNN and ongoing supervisor for 
several master and PhD students. 
The project group possesses long experience in research project management and has a firm 
background in clinical research and epidemiology. The project organization ensures a solid foundation for 
research collaboration and knowledge transfer between the specialist healthcare, primary healthcare and 
health care planners. The project will be an important meeting place and can provide experience and contacts 
in planning future research projects. The projects approach facilitates a strong, long lasting and 
interdisciplinary regional and national research environment anchoring:  
Ellisiv B. Mathiesen (Head of Brain and Circulation Research Group, UiT), Maja-Lisa Løchen (Head of 
Department, Department of Clinical Medicine, UiT), both with extensive experience from the Tromsø Study 
and AF research. Ekaterina Sharashova (assoc. professor, Dept. of Community Medicine, UiT and principal 
investigator of the project "Atrial fibrillation in the Tromsø Study 1986-2017: incidence trends, contribution 
of risk factors and prognostic outcomes"), Hilde Espnes (MD, PhD candidate), Assami Rössner (cardiologist 
responsible for echocardiography examination in T8) and Iina Marja Javo (consultant cardiologist, UNN), Erin 
Hald (hematologist, UNN involved in AF research). The last three mentioned participants also hold positions 
as assoc. professors, Dept. of Clinical Medicine, UiT. Jannike Ringstad is user representative from LHL.  
A broad national collaboration is assured by including leading capacities within the field in the project 
group, namely Halvor Øygarden and Jarle Jortveit (Sørlandet Sykehus) involved in the AF-study and 
NORSCREEN, Jon Magne Letnes and Håvard Dalen (HUNT/NTNU) chairing AF-studies in HUNT, Håkon Ihle 
Hansen (Vestre Viken), Guri Hagberg (OUS) involved in AF-studies in ACE 1950. In addition, Renate Schnabel 
(University Heart Centre Hamburg) is an international collaborator with expertise on AF and biomarkers.  
3.2 PROJECT ORGANISATION AND MANAGEMENT 
The role of the PhD candidate: The PhD candidate will be recruited and employed in a 50% position from 
April 2025. Prior to start all relevant approvals (REC and PVO) will be obtained by the project leader. The PhD 
candidate will work in close collaboration with the Tromsø Study group, utilizing available infrastructure 
provided by the Tromsø Study.  Tromsø 8 starts in march 2025 with the first visit. 10,000 participants will 
subsequently be invited to visit 2 starting in April 2025, where NT-proBNP is measured. Based on NT-ProBNP 
results, participants will be selected and long-term recordings with ECG247 are conducted. The infrastructure 
at T8 will be essential for conducting blood tests and ECG247 sensor logistics. The management of the 
ECG247 sensor monitoring is performed by specially trained nurses, but the PhD candidate will be involved 
in this work to have first line details of the workflow. Postal deliveries of sensors for self-administration will 
be performed together with the research nurses. General feedback to the Tromsø participants will be 
standardized and provided electronically. The PhD candidate will under supervision develop an information 
video in collaboration with LHL. The PhD candidate will organize the data bases and perform data analyses, 

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drafting and revision of manuscripts according to timeline presented the electronic application form and 
Gantt chart below. The candidate will be affiliated with the research group Brain and Circulation at UiT and 
have a shared office space with other PhD students. The candidate will join the national AFIB network 
(afib.no) and the Norwegian PhD school of heart research (NorHeart (norheart.no)). The four manuscripts of 
the PhD project will address research questions 1-4 and will be published in international peer-reviewed 
journals. Furthermore, the PhD student will participate in the PhD program for medicine and health sciences 
at UiT, which includes completing at least 30 credits of required coursework. 
User involvement: LHL provides knowledge from the patients’ perspective for the studies’ design, planning 
and performance. LHL has been involved in planning of the specified study. Their contribution to the 
assessment of health-related life quality of life has been valuable and impacted on the project’s objectives. 
They will be included in ongoing discussion related recruitment enhancement, information to the participants 
as well as experience with the use of ECG247 sensors for monitoring. LHL will also be actively involved in 
discussion and dissemination of the results. The research staff will participate in meetings arranged by LHL 
to present relevant findings. These face-to-face meetings will provide valuable feedback to optimize research 
and clinical implementation towards what is most important for patients with AF and stroke. 
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