Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study

Aims Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study.Methods and results Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations.Conclusion Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients. Graphical Abstract Twelve biomolecules selected to reflect different disease processes were quantified in 433 patients undergoing a first atrial fibrillation (AF) ablation (64 years; 33% women) in the AXAFA-AFNET5 biomolecule study. Biomolecule concentrations were associated with recurrent AF after AF ablation. After adjustment for clinical features and randomized treatment, NT-proBNP [Hazard Ratio (HR) 1.58, 95% CI (1.29, 1.94)], angiopoietin 2 [ANGPT2, HR 1.37 (1.12, 1.67)], and bone morphogenetic protein 10 [BMP10, HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF. These results suggest that the disease processes leading to elevation of these biomolecules, including disturbed atrial cardiomyocyte metabolism, altered shear stress, and increased load, contribute to recurrent AF after ablation in patients.