Role of atrial high-rate episodes in stratifying thromboembolic risk: a multiple cut-off diagnostic meta-analysis

Aims: Despite the high prevalence rate of atrial high-rate episodes (AHREs) detected using cardiac implantable electronic devices (CIEDs), clinical guidelines and consensus documents have disagreed on a universal AHRE definition and a temporal cut-off related to subsequent thromboembolic events. This diagnostic test accuracy meta-analysis aims to derive the optimal temporal threshold of clinically significant AHREs from the available literature. Methods: The PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting the incidence of thromboembolic events related to at least one AHRE temporal cut-off. A total of 23 studies were included: 19 considering the longest single AHRE and four the AHRE burden, respectively. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed. Two analyses were performed according to the AHRE temporal cut-off subtype (longest episode vs. cumulative burden). Results: The analysis on the longest single AHRE indicated 0.07 min as the optimal duration to differentiate AHRE associated or not with thromboembolic events [sensitivity 65.4% (95% CI 48.8%-79.0%), specificity 52.7% (95% CI 46.0%-59.4%), and area under the summary receiver operating characteristic curve (AUC-SROC): 0.62]. The analysis on AHRE burden indicated 1.4 min as the optimal cut-off [sensitivity 58.2% (95% CI 25.6%-85.0%), specificity 57.5% (95% CI 42.0%-71.7%), and AUC-SROC 0.60]. A sensitivity analysis excluding patients with a history of atrial fibrillation and including high-quality studies only yielded similar results. Conclusion: The presence of AHRE, rather than a specific duration, relates to an increased, albeit low, thromboembolic risk in CIED patients. Any AHRE should constitute an additional element in patient-specific thromboembolic risk assessment.