Evaluating the Impact of Home-Based Sleep Apnea Diagnostic on Well-Being, Health Behavior, and AF Load in Patients With Atrial Fibrillation Using a Decentralized Platform

Background \& Clinical Relevance Atrial fibrillation (AF) is often described as reaching epidemic proportions. On a societal level, methods using new technology are needed as hospitals and payers need to rethink how to manage future care for patients with AF. For the patient, risk factor management is crucial to ensure optimal care, lowering the burden of hospitalizations, promoting physical and mental health behavior and increasing Quality of Life (QoL).

In recent years an integrated approach to management of AF has been recommended including focus on optimal risk factor evaluation such as hypertension, diabetes, smoking, and obesity. Presence of obstructive SA in relation to AF has recently also been established as an important modifiable risk factor. SA refers to intermittent, cessations or reductions of airflow during sleep and is accompanied by hypoxia, sleep arousals, and hemodynamic changes. The most prevalent form is obstructive sleep apnea (SA) with partial or complete collapse of the upper airway. OSA activates the sympathetic nervous system during respiratory events. This potentiates vasoconstriction which often triggers an increase in blood pressure and heart rate which is the suggestive mechanism behind the link to AF. The diagnosis of SA is based on the number of apneas and hypopneas per hour of sleep, i.e. the Apnea-Hypopnea Index (AHI). SA is categorized as mild (5-14 AHI), moderate (15-29 AHI) or severe (≥ 30 AHI).

Some centers report up to 85% of AF patients having SA, and our 126-patient study of an all-comer Danish population shows 56% with moderate to severe SA, which should be eligible for treatment. SA treatment typically includes continuous positive airway pressure (CPAP) if moderate or severe SA is present (i.e. an AHI of \>15 per hour). Interestingly, presence of SA has not been given the same attention as ensuring adequate blood pressure, weight control or diabetes management in AF. Despite this, overwhelming evidence suggests that AF patients with OSA receiving CPAP treatment are less likely to have AF recurrences after 12 months following cardioversion compared to AF patients not receiving CPAP treatment. Additionally, several nonrandomized observational studies indicate that CPAP can help maintain sinus rhythm after ablation in patients with AF who have OSA, and need for antiarrhythmic drugs are less needed in CPAP treated AF patients . Due to daytime sleepiness and fatigue, SA in itself may be a possible causal factor for physical inactivity and in addition lowering general state of health.

These findings highlight that SA is critically unrecognized and therefore undertreated, particularly in patients with AF. Current guidelines recommend screening of AF (IIa recommendation) in patients with SA, but unclear on how to approach SA in AF patients in terms of how and when to test for SA. Though SA is a trigger for cardiac arrhythmia and a substrate for AF maintenance and progression, it is uncertain if systematic screening of SA in patients with AF is beneficial. Importantly, it has been shown that standard SA screening questionnaires fail to capture high-risk individuals with AF and consequently the benefit in a larger scale SA evaluation is poor. The gold standard of SA diagnosis with polysomnography (PSG) or cardiorespiratory monitoring (CRM) is information rich but is cumbersome, time-consuming and not widely available. Several sensors and belts measuring posture, chest movement, abdominal movement and nasal airflow are used. Often it includes an overnight stay or at least three hospital visits (instruction for application, return of the device and follow-up visit for the results).

Therefore, a new approach to manage AF patients for SA evaluation including estimating the clinical effect is needed. A proof-of-concept of a virtual management pathway has recently been suggested which are incorporated in this proposal. In VIRTUAL-SAFARI, AF patients awaiting ablation were offered education on the impact of concomitant OSA followed by information on a virtual sleep-disordered breathing project setup. The setup included digital referral to virtual sleep laboratory, home sleep test, results and data submission, virtual consultation, and CPAP treatment in the majority of the app. 50% diagnosed with SA. Indeed, emerging new technologies consisting of miniaturized monitoring devices and accurate algorithm development may transform how patients and clinicians approach risk factor management. Together with increased awareness from regulators of the benefits of virtual (or decentralized) trials (i.e. reduced or no site visits from patients) in the COVID era, current research practice but also future patient management need to consider how incorporating innovative methods can improve care, patients-related outcomes and prognosis. Notably, it is paramount when implementing new patient care pathways that evidence is based on unbiased and independent research and not pushed by commercial or industrial stakeholders. Our pilot trial, Mini VIR-SAAF, successfully demonstrated the feasibility of a completely decentralized clinical trial setup, confirming the proof of concept with the inclusion of 20 participants. The use of home-evaluation for SA, physical tracking and heart rhythm monitoring was well-received, with only one participant dropping out. This low drop-out rate indicates strong participant engagement and satisfaction. Given these positive results, the investigators are confident in scaling up the project to a national level, building on the insights gained to further optimize participant onboarding and study commitment.

Study Design This is an investigator-initiated virtual (or decentralized) trial that includes a postal parcel (mail-in) containing sensors for SA diagnosis (WatchPAT One) and physical activity (SENS Motion), in addition to smart-phone based heart rhythm (FibriCheck) monitoring in participants with paroxysmal or persistent AF. A case-coordinator (the investigators) will manage all participant contacts virtually during the study from inclusion to follow-up.

Sign-up for inclusion Participants interested in participating in the study can sign up on our website, www.vir-saaf.dk. In the registration form, participants will be asked to provide their full name, email, phone number, and the region they live in. Additionally, they will be asked if they have been diagnosed with AF and if they have ever undergone any SA testing. This information will serve as an initial screening for study eligibility. The data collected from the registration form will be securely stored in RedCap.

Inclusion:

After signing up on the webpage, participants will be called by telephone by the investigators to be further informed of the study. Subsequently, participants will be invited to the Introduction Video Meeting via an SMS with a link to a video meeting. At the Introduction Video Meeting, the participants will receive oral information about the study. Also digital written information with full details of the study ("Deltager information" and "Før du beslutter dig"), including risks and benefits, will be available to potential participants. Please see the section "Recruiting and Giving Consent" below for a detailed description of obtaining informed consent from participants.

After the Introduction Video Meeting, eligible participants accepting to participate will be able to download our application, through which written informed consent via MitID will be obtained. Once consent has been given, final confirmation of study eligibility will be performed by entering key variables into a secure web-based program (RedCap) at the Cardiovascular Research Center at Herlev-Gentofte Hospital.

After inclusion, participants who answer digital questionnaires (Survey 1) will receive a mail-in package containing either the WatchPAT One device and the SENS Motion device (intervention group) or only the SENS Motion device (control group). The Survey 1 will include basic participant information (such as email, address, height, weight, self-measured neck circumference \[important measurement in sleep apnea\], and employment status \[important factor to assess physical activity patterns\]) and the following questionnaires: Atrial Fibrillation Effect on QualiTy-of-life (AFEQT), AF Severity Scale (AFSS), Pittsburgh Sleep Quality Index (PSQI), and The eHealth Literacy Questionnaire (eHLQ). Please see document 08.01 for the complete questionnaires.

Furthermore, a clinical evaluation form will be filled out by the investigators based on electronic charts or from the Introduction Video Meeting, which includes: CPR number, sex, birth date, questions related to AF (modified European Heart Rhythm Association (mEHRA) symptom classification (0-4)), concomitant CVD medication (antithrombotic medication, rate-lowering drugs, anti-arrhythmic drugs), date of first AF detected, type of AF (paroxysmal or persistent AF), and other relevant medical conditions.

Randomization Automatic patient randomization in the two arms (ratio 2:1) will be performed in R-studio. The randomization key will be stored in a locked and secure environment at the Cardiovascular Research Center at Gentofte Hospital. The primary endpoint will be evaluated and determined by an independent committee blinded to randomization.

Postal Parcel 1:

After completing Survey 1, a postal parcel (postal parcel 1) including either the WatchPAT One device and the SENS Motion (intervention) or only the SENS Motion (control) will be sent to the participant's address. The postal parcel 1 will also include detailed written information and instructions for the devices and applications together with a user-friendly written overview of the study design. As soon as the participants receive the postal parcel 1, the participant will begin their home monitoring with the 1 night of WatchPAT One monitoring (only intervention group), the 7 days of activity tracker (round 1) with SENS Motion, and daily heart rhythm monitoring with the FibriCheck application.

During the home monitoring, if the participants have any questions, concerns or difficulties using devices or applications, a telephone number will be given to contact the investigators directly. Also, a frequently-asked question section is made available to the participants in the VIR-SAAF trial app.

Return of equipment 1:

After completing the 7 days of activity tracker round 1 with SENS Motion, the participants will ship the used SENS Motion device back to the investigators. This will be done via a prepaid shipping label for Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Gentofte Hospitalsvej 1, 2900 Hellerup. The WatchPAT One is a disposable (intervention group) and the participants receiving the device are thoroughly informed how to discard the device correctly (electronic waste). No data is stored on the device.

SA evaluation in cooperation with the Danish Center for Sleep Medicine, Glostrup:

Participants in the active arm will be scheduled for a SA Evaluation Video Meeting with the investigators.

In case the evaluation shows no or only mild SA the participants are informed that the evaluation did not show any signs of significant SA. If a participant reports a major degree of symptoms that could be a result of SA, a referral to a sleep physician will be done.

In case the evaluation shows moderate to severe SA, the participants are informed that the evaluation shows signs of significant SA that should be evaluated for indication for treatment. If accepting, the participants will be referred to a sleep physician for clinical assessment of diagnosis and potential treatment.

Dansk Center for Søvnsygdomme (Glostrup Hospital, Copenhagen) will be the primary center for the clinical assessment. However, local sleep centers, if accepted, will also be involved in the clinical assessment

• AF load [Срок оценки: 18 weeks]
• Physical health behavior [Срок оценки: 18 weeks]
• Symptom severity [Срок оценки: 18 weeks]