Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: a systematic review and meta-analysis

Abstract

Abstract Background Sub-clinical atrial fibrillation (SCAF) and atrial high-rate episodes (AHREs), seen as high-frequency atrial tachyarrhythmias in patients with cardiac implantable electronic devices (CIEDs), have gained prominence as determinants of clinical atrial fibrillation (AF) and increased stroke risk. As a result, several studies investigating their role in predicting the onset of AF and AHRE-related outcomes have been conducted but uncertainty exists on the epidemiology of AHRE. Purpose To estimate the incidence of SCAF, according to presence of AHREs in patients with CIEDs, through a systematic review and meta-analysis of the available literature. Methods PubMed and EMBASE were searched from inception to 27th January 2021 for all studies documenting the incidence of AHREs in patients with CIEDs. We included all studies with ≥100 patients reporting data on AHREs incidence. Pooled prevalence and incidence rates were computed; we also performed meta-regressions for pooled incidence rates, according to relevant study-level characteristics. This study was registered in PROSPERO: CRD42019106994. Results Among the 2,515 results retrieved, we included 51 studies in the systematic review and meta-analysis, with a total of 68,414 patients. Meta-analysis of included studies showed a pooled prevalence of 28.2% (95% CI: 24.3–32.5%, I2=99%), with a pooled incidence rate (IR) of 15 new AHRE cases per 100 patient-years (95% CI: 12–19, I2=100%). Given the large heterogeneity showed in the pooled estimates we performed additional analyses. Regarding pooled prevalence, we performed several subgroup analyses, according to various studies baseline characteristics, which did not show any significant difference in any of the subgroups examined. Regarding IR, a multivariable meta-regression analysis showed that decreasing follow-up time and increasing age were the only factors significantly associated with AHRE incidence, explaining a large proportion of heterogeneity (R2=68%, p<0.001; Figure 1, Panel A and B respectively). Accordingly, the AHRE IR was highest at 1 year follow-up and in the oldest subjects. Presence of SCAF was significantly associated with older age, higher CHA2DS2-VASc score, and higher prevalence of hypertension, heart failure and history of cerebrovascular disease. Conclusions This systematic review and meta-regression demonstrated that SCAF is very common in patients with CIEDs, with an overall IR for AHREs of up to 15 per 100 patient-years; increasing with age and decreasing with longer follow-up time. Presence of SCAF was associated with an overall higher clinical risk profile compared to those subjects without SCAF. Funding Acknowledgement Type of funding sources: None. Figure 1. Meta-regression for AHRE Incidence