A multiple cut-off diagnostic meta-analysis to identify the atrial high-rate episodes threshold that better relates to thromboembolic events

Abstract

Abstract Background Despite the high prevalence of atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices (CIED), clinical guidelines and consensus documents have failed to agree on a universal AHRE definition. Clear evidence on the best management strategy is lacking. Purpose The present is a diagnostic test accuracy meta-analysis aiming to derive from available literature the optimal AHRE threshold to predict thromboembolic events. Methods PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting incidence of thromboembolic events referred to at least one AHRE definition. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed: duration of AHRE was the "diagnostic test" (positive test if the patients experienced an AHRE lasting at least as long as the time cut-off under examination) whose performance in predicting the "disease" (thromboembolic events) was evaluated across multiple cut-offs. Two analyses, according to AHRE definition (longest episode vs. cumulative burden), were performed. Results 23 studies were included in the analyses (Fig. 1 Panel A), encompassing 46,189 patients: 19 considering the longest single AHRE and 4 the AHRE burden, respectively. Median follow-up was 40.75 (IQR 28.25-52.80) months. The analysis on the longest single AHRE indicated 0.07 minutes as the optimal cut-off to differentiate AHRE associated or not to thromboembolic events [sensitivity 65.4% (95% CI 48.8-79.0%), specificity 52.7% (95%CI 46.0-59.4%), area under the summary receiver operating characteristic curve (AUC-SROC): 0.62; Fig. 1 Panel B]. The analysis on AHRE burden indicated, instead, 1.4 minutes as the optimal cut-off [sensitivity 58.2% (95%CI 25.6-85.0%), specificity 57.5% (95% CI 42.0-71.7%), AUC-SROC 0.60; Fig. 1 Panel C]. PPV and NPV for 6 minutes and 24 hours cut-offs were similar in each analysis (Figure 2). Sensitivity analyses exclusively considering studies reporting data on patients without previous AF diagnosis and high-quality studies only yield similar results. Conclusion The present evidence-based approach suggests the presence (or not) of AHRE, rather than a specific duration, relates to an increased thromboembolic risk in CIED patients. A linear relationship between AHRE duration (both in terms of single longest episode than cumulative burden) and thromboembolic events was not observed.