Screening with an implantable loop recorder (ILR) for atrial fibrillation (AFib) is associated with a significant reduction in stroke and systemic embolism (SE) in individuals with a higher genetic risk of AFib, but not those with lower genetic risk, according to a prespecified post hoc analysis of the randomized LOOP study published Oct. 29 in JACC. The findings indicate that genetic predisposition may help select individuals who benefit from AFib screening.

Oliver B. Vad, MD, PhD, et al., evaluated 5,656 AFib-naïve individuals aged ≥70 years with stroke risk factors and available genetic data. The prespecified post hoc analysis randomized participants 1:3 for screening with an ILR vs. usual care, and genetic risk of AFib was assessed using polygenic risk scores (PRS). Interaction between the randomization arm and PRS for AFib (PRSAFib) was assessed in cause-specific Cox regressions for the full cohort and across the observed range of polygenic risk using a continuous prediction grid.

The primary outcome was a composite of stroke and SE. Secondary analyses included models stratified by PRS level, gene-screening interactions for major bleeding events, and associations between PRSAFib and AFib burden, which was defined as one or more episodes lasting ≥24 hours among participants with ILR-detected AFib.

Of included participants (median age of 73 years, 47% women) with a median follow-up of 5.4 years, 969 participants (17%) were diagnosed with AFib, 296 (5%) had stroke or SE and 206 (3%) had major bleeding. Additionally, PRSAFib was associated with higher rates of AFib (hazard ratio [HR] per standard deviation increase, 1.2; p<0.001), and there was a significant interaction between ILR screening and PRSAFib for stroke and SE (Pinteraction =0.006).

In participants with PRSAFib ≥median, ILR screening was associated with lower rates of stroke and SE (HR, 0.65; p=0.036), but not in participants with PRSAFib <median (HR, 1.06; p=0.75). Of note, ILR screening was associated with higher rates of major bleeding at lower levels of PRSAFib (Pinteraction =0.036), corresponding to an HR of 1.71 (p=0.011) in those with PRSAFib <median. A 1-SD increase in PRSAFib was associated with an odds ratio of 1.35; p=0.037) for having one or more AFib episode lasting ≥24 hours.

"Our findings expand the [genetic screening] field, indicating that the use of genetics in screening could be applied to a broader range of disorders, including cardiovascular diseases," write Vad, et al. "At the present, findings on genetic data from current trials on [AFib] screening may provide insights into what might be expected from future trials on genetically guided [AFib] screening."

In an accompanying editorial comment, Michael J. Domanski, MD, FACC; Timm-Michael L. Dickfeld, MD, PhD; and Colin O. Wu, congratulate the authors for "adducing results that importantly extend our understanding in [two] ways." "First, they suggest the possible preventive value of screening for device-detected [AFib] when it is applied to a cohort of individuals with sufficiently elevated risk for [AFib]. Second, it demonstrates the utility of a practical-to-ascertain genetic test that identifies individuals at high risk for [AFib]."