National Decentral/Virtual Randomized Trial Testing Remote Sleep Apnea Evaluation in Patients With Atrial Fibrillation

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.