By Joshua Moss, MD

Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco

Dr. Moss reports he is a consultant for Abbott, Biosense Webster, and Boston Scientific.

SYNOPSIS: In older patients with risk factors for stroke drawn from the general population, previously undiagnosed and asymptomatic episodes of atrial fibrillation are detected frequently via implantable loop recorder monitoring, allowing for early initiation of anticoagulation therapy.

SOURCE: Diederichsen SZ, Haugan KJ, Brandes A, et al. Natural history of subclinical atrial fibrillation detected by implanted loop recorders. J Am Coll Cardiol 2019;74:2771-2781.

There is evidence to suggest subclinical episodes of atrial fibrillation (AF) — those detected only incidentally — are associated with a higher risk of stroke. Diederichsen et al sought to characterize burden, progression, symptoms, and heart rates associated with subclinical AF.

Subjects enrolled in the LOOP study (Atrial Fibrillation Detection by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals) were invited to participate from the general population. Eligible subjects had no history of AF, were at least 70 years of age, and presented with at least one additional risk factor for stroke: hypertension, diabetes, heart failure, or prior stroke. Subjects were randomized in a 1:3 ratio to receive an implantable loop recorder (ILR) or be assigned to a control group. Arrhythmia monitoring continued until end of ILR battery life (minimum three years), device explanation, initiation of antiarrhythmic treatment, or death. Subjects with AF episodes detected by the ILR and adjudicated by two cardiologists were offered oral anticoagulation and clinical follow-up. The primary endpoint was cumulative AF burden, including all episodes lasting at least six minutes.

A total of 590 individuals with day-to-day data retrieval from an ILR were monitored for a median of 40.2 months. Thirty subjects died during that period, with mortality attributed to cancer in 53% and cardiovascular disease in 33%. More than one-third experienced adjudicated AF episodes lasting at least six minutes, 92% of whom then started oral anticoagulation. However, median overall AF burden was only 0.13%, and only 18 of the 205 subjects with AF had a burden > 5%. Anticoagulation initiation rates did not differ significantly relative to arrhythmia burden detected. Mortality was higher in subjects with AF detected during the first year of follow-up, with a hazard ratio of 4.51 (95% confidence interval, 2.08-9.58).

In a multivariate model, older age and higher NT-proBNP were independently associated with significantly higher odds of AF detection (the odds ratio was 1.33 for every five-year increment in age). However, in the subset of participants with newly detected AF, younger age was associated with higher overall arrhythmia burden, as well as male gender and history of hypertension.

Regarding arrhythmia progression, 55.1% of subjects in whom AF was detected showed an overall decrease in AF burden over the subsequent monitoring period, and 22% exhibited complete remission of AF over the last six months of monitoring. Only 16% developed episodes of AF lasting > 24 hours, the vast majority of whom initially experienced shorter episodes (many at least six months before the first 24-hour episode). Only 6.3% of subjects experienced episodes lasting longer than seven days. Many patients with newly detected AF reported no symptoms (90% denied symptoms upon initial diagnosis, and few went on to trigger symptom-episode recordings on the ILR thereafter). Those who did report symptoms at the time of the initial episode tended to record higher heart rates in AF (median 122 beats per minute vs. 95 beats per minute in subjects without symptoms).

COMMENTARY

In the era of wearable and direct-to-consumer devices for heart rate and rhythm monitoring, detection of AF in the absence of any symptoms undoubtedly will become more common. The data gathered and presented thus far as part of the LOOP study are valuable in helping clinicians understand what to expect in older, asymptomatic patients with risk factors for stroke who start some form of long-term arrhythmia monitoring (whether self-motivated or on the advice of a physician). Chances are good that AF will be detected within several years in these patients, as it was in 35% of study subjects monitored with an ILR.

There were multiple limitations to this study, well described by the authors in their manuscript, related to specific statistical techniques, possible selection bias introduced by the inclusion criteria, and the likelihood of inconsistent symptom reporting. Perhaps more important is a crucial unanswered question: Will the therapies typically used for symptomatic AF (and/or AF detected by intermittent routine monitoring such as in-office ECGs) lead to more harm or good overall? Other researchers have demonstrated that even short, subclinical episodes of AF detected by a cardiac implantable electronic device (CIED) are associated with higher risk of stroke. Still, the population studied here was different from other populations with AF in several ways. First, subjects did not have an indication for a CIED (nor necessarily the comorbidities associated with such patients). Second, subjects did not exhibit the symptoms that brought most previously studied AF patients to medical attention. Third, subjects’ overall arrhythmia burden remained low, with more than one in five demonstrating complete spontaneous regression by the end of the monitoring period. Additionally, overall heart rates were not dramatically higher in patients diagnosed with AF, and remained, on average, slower than 100 beats per minute, even during AF in the few patients with higher (> 5%) arrhythmia burden.

Therefore, it is conceivable that automatic initiation of therapeutic anticoagulation when AF is detected in such a way might fail to significantly reduce stroke risk while still increasing risk of bleeding complications disproportionately. Similar dilemmas exist for initiation of rate-controlling medications, antiarrhythmic drugs, or ablation therapy. Until longer-term outcomes comparing the ILR group to the control group in the LOOP study are published, it still makes sense to favor anticoagulation for patients with incidentally diagnosed (and self-diagnosed) AF with other stroke risk factors. But more than ever, it will be crucial for clinicians to understand and convey relative risks and benefits about potential downstream tests, medications, and procedures.