Atrial High-Rate Episode Duration Thresholds and Thromboembolic Risk: A Systematic Review and Meta-Analysis

Abstract

Background Available evidence supports an association between atrial high-rate episode (AHRE) burden and thromboembolic risk, but the necessary extent and duration of AHREs to increase the thromboembolic risk remain to be defined. The aim of this systematic review and meta-analysis was to identify the thromboembolic risk associated with various AHRE thresholds. Methods and Results We searched PubMed and Scopus until January 9, 2020, for literature reporting AHRE duration and thromboembolic risk in patients with implantable electronic devices. The outcome assessed was stroke or systemic embolism. Risk estimates were reported as hazard ratio (HR) or relative risk alongside 95% CIs. We used the Paule-Mandel estimator, and heterogeneity was calculated with I² index. Among 27 studies including 61 919 patients, 23 studies reported rates according to the duration of the longest AHRE and 4 studies reported rates according to the cumulative day-level AHRE duration. In patients with cardiac implantable devices, AHREs lasting ≥30 seconds significantly increased the risk of stroke or systemic embolism (HR, 4.41; 95% CI, 2.32-8.39; I², 5.5%), which remained consistent for the thresholds of 5 minutes and 6 and 24 hours. Patients with previous stroke or transient ischemic attack and AHREs lasting ≥2 minutes had a marginally increased risk of recurrent stroke or transient ischemic attack. The risk of stroke or systemic embolism was higher in patients with cumulative AHRE ≥24 hours compared with those of shorter duration or no AHRE (HR, 1.25; 95% CI, 1.04-1.52; I², 0%). Conclusions This systematic review and meta-analysis suggests that single AHRE episodes ≥30 seconds and cumulative AHRE duration ≥24 hours are associated with increased risk of stroke or systemic embolism.

Keywords: atrial high‐rate episode; embolism; implantable device; stroke.

Figure 1. Incidence rates of stroke or systemic embolism per 100 patient‐years in patients with atrial high‐rate episode (AHRE) burden above the reported threshold (top panel) and patients with AHRE burden below the reported threshold or no AHRE (bottom panel).

Studies reporting on the longest single AHRE duration are summarized in the top panel, whereas studies reporting on the cumulative day‐level AHRE burden are summarized in the bottom panel. The reported data from Swiryn et al did not allow the calculation of incidence rates. *Denoted studies of patients with previous stroke or transient ischemic attack.

Figure 2. Risk estimates (hazard ratio [HR]/relative risk [RR]) and 95% CIs for the risk of stroke or systemic embolism based on the duration of the longest atrial high‐rate episode (AHRE).

Studies are listed by the AHRE threshold. Boxes represent the HRs/RRs and lines represent the 95% CIs for individual studies. All patients included in the analysis for the threshold of 2 minutes had prior embolic stroke of undetermined source or transient ischemic attack and were monitored with implantable loop recorders. All other patients included in this analysis had a cardiac implantable electronic device because of heart failure or significant dysrhythmias.

Figure 3. Risk estimates (hazard ratio [HR]/relative risk [RR]) and 95% CIs for the risk of stroke or systemic embolism based on the cumulative day‐level duration of atrial high‐rate episodes (AHREs).

Studies are listed by the AHRE threshold. Boxes represent the HR and lines represent the 95% CIs for individual studies. All studies reported risk estimates for stroke, except from the study of Shanmugam et al.