Effects of Systematic Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: a Secondary Analysis of the Randomized LOOP Study.

Abstract

Research suggests N-terminal pro-B-type natriuretic peptide (NT-proBNP) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. This study aimed to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. In the LOOP Study, 6004 AF-naïve individuals aged 70-90 years with additional stroke risk factors were randomized 1:3 to either continuous screening with implantable loop recorder (ILR) and anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care (Control). This post-hoc analysis included the study participants with available NT-proBNP measurement at baseline. A total of 5819 participants were included (mean age 74.7 years (standard deviation, 4.1), 47.5%females). The median NT-proBNP level was 15 pmol/L [interquartile range: 9-28], corresponding to 125 pg/mL [interquartile range: 76-233]. NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio (HR) 1.84 [95% confidence interval (CI): 1.51-2.25]) and the Control group (HR 2.79 [95% CI: 2.30-3.40]). Participants with NT-proBNP above median were also at higher risk of clinical events compared with those having lower levels (HR 1.21 [95% CI: 0.96-1.54] for stroke or systemic embolism (SE), 1.60 [95% CI: 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI: 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (HR 0.60 [95% CI: 0.40-0.90] and 0.70 [95% CI: 0.53-0.94], respectively), but not among those with lower levels (pinteraction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus Control (pinteraction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. In an elderly population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels, but not among those with lower levels. These findings should be considered hypothesis-generating and warrant further study before clinical implementation.