Abstract

BACKGROUND AND AIMS: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm-control therapy. Predictors of attaining sinus rhythm at follow-up are not well known. METHODS: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 46% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets. RESULTS: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). External validation confirmed that low concentrations of ANGPT2, BMP10 and NT-proBNP predict sinus rhythm during follow-up. CONCLUSIONS: Low concentrations of ANGPT2, BMP10 and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.