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

BACKGROUND: Different disease processes can combine to cause to atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. OBJECTIVE: 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: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, 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 three months after AF ablation. RESULTS: 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. CONCLUSIONS: Elevated concentrations of ANGPT2, BMP10 and NT-proBNP are associated with recurrent atrial fibrillation after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to atrial fibrillation after AF ablation in patients.