Subclinical and Device-Detected Atrial Fibrillation: Pondering the Knowledge Gap: A Scientific Statement From the American Heart Association

Abstract

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus.

Keywords: AHA Scientific Statements; ambulatory monitoring; atrial fibrillation; cardiac arrhythmia; cardiac pacing; cerebrovascular stroke; pacemaker.

Figure 1.. A “tip of the iceberg” analogy describes the spectrum of apparent and subclinical atrial fibrillation in terms of the method/context of detection and clinical significance.

ESUS indicates embolic stroke of undetermined source; and RF, radiofrequency. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved. Copyright © 2019, Mayo Foundation for Medical Education and Research.

Figure 2.. The devices that allow detection of subclinical atrial fibrillation exist on a spectrum from minimally invasive devices, or wearables, to permanent implanted devices and provide intermittent to continuous surveillance for events.

A, Apple Watch. Copyright © Shutterstock/Alexey Boldin. B, ZIO^® XT Patch. Used with permission of iRhythm Technologies, Inc. Copyright © iRhythm Technologies, Inc. C, Holter or event monitor. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved. Copyright © Mayo Clinic. D, Reveal LINQ^™. Courtesy of Medtronic. E, Implanted pacemaker or defibrillator. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved. Copyright © Mayo Clinic.

Figure 3.. A Lorenz plot depicts variability in RR intervals as the δRR(n) on the “n beat” on the y axis and the δRR(n-1) on the “N-1 beat” on the x axis.

Regular rhythms cluster around the origin; atrial fibrillation (AF) is marked by scatter of the RR intervals; and premature atrial contractions (PACs) are represented as clusters of points on the Lorenz plot. AT indicates atrial tachycardia.

Figure 4.. In ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial), the cumulative event rate for cardioembolic events was highest in patients with subclinical atrial fibrillation (SCAF) >24 hours in duration as demonstrated by these extended Kaplan-Meier curves of ischemic stroke/systemic embolism stratified by time-dependent durations of SCAF.

Adapted from Van Gelder et al by permission of the European Society of Cardiology. Copyright © 2017, The Author. Published on behalf of the European Society of Cardiology.

Figure 5.. Hazard ratio (HR) for thromboembolism reported in previous studies plotted as a function of the log of the duration of the longest episode of atrial fibrillation (AF) detected (with a trend line).

ASSERT indicates Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial; MOST, Mode Selection Trial; RATE, Registry of Atrial Tachycardia and Atrial Fibrillation Episodes; SOS AF, Stroke Prevention Strategies Based on Atrial Fibrillation Information From Implanted Devices; and TRENDS, A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics. Reproduced with permission from Steinberg and Piccini. Copyright © 2018, American Medical Association. All rights reserved.

Figure 6.. In ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial), many stroke/systemic embolism events were not temporally associated with subclinical atrial fibrillation (SCAF) episodes.

Each row represents data collected from each of 18 patients who had SCAF within 1 year before or after the event. Total hours of atrial episodes per day are denoted by the height of each dark gray vertical line. Gray-shaded areas correspond to the period of continuous monitoring with cardiac device. Asterisks and black dashed lines denote use and period of oral anticoagulation therapy. Modified from Brambatti et al. Copyright © 2014, American Heart Association, Inc.

Figure 7.. The association between atrial fibrillation (AF) and stroke can be conceptualized by 2 models: AF as a risk marker or AF as a direct cause of stroke.

These concepts have implications for the treatment and definition of a critical clinically relevant threshold of AF burden or duration. LAA indicates left atrial appendage; and PAF, paroxysmal atrial fibrillation.

Figure 8.. A pooled analysis of 3 prospective studies (TRENDS [A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics], PANORAMA [Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy], and SOS AF [Stroke Prevention Strategies Based on Atrial Fibrillation Information From Implanted Devices]) found that longer initial episodes of subclinical atrial fibrillation (AF) were associated with the development of AF lasting ≥23 hours.

Data derived from Boriani et al.

Figure 9.. A potential approach to patients with subclinical atrial fibrillation (SCAF) could consider both patient risk (as gauged by the CHA₂DS₂-VASc score) and SCAF burden/duration.

A, Patients at low risk or with short and infrequent atrial high-rate episodes (AHREs) do not require anticoagulation. B, Patients with intermediate risk and AHREs lasting >6 minutes to 24 hours are an uncertain population but are currently under study in 2 prospective randomized controlled trials. C, Patients at high risk with longer episodes could be considered reasonable candidates for anticoagulation, although the precise threshold for SCAF duration remains uncertain. AF indicates atrial fibrillation; ARTESiA, Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Subclinical Atrial Fibrillation trial; COMMANDER HF, A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure; COMPASS, Cardiovascular Outcomes for People Using Anticoagulation Strategies; NOAH, Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes Trial; and OAC, oral anticoagulation. Modified from Freedman et al with permission. Copyright © 2017, Springer Nature.

Figure 10.. The benefit of anticoagulation can be conceptualized as a balance between stroke and bleeding risks with and without anticoagulation.

Non-vitamin K antagonist oral coagulants randomized controlled trial data in the non-atrial fibrillation population (eg, COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], COMMANDER HF [A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure], NAVIGATEESUS [New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source]) could help estimate the balance of risk in SCAF. CKD indicates chronic kidney disease; Diab, diabetes mellitus; HF, heart failure; HTN, hypertension; SCAF, subclinical atrial fibrillation, and Vasc, vascular disease.