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

Figures

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  Figure 1. Flowchart of patients included in analysis. Patients without blood samples and quantified biomarkers at both time points (pre-ablation and 3 months post-ablation) were excluded. Apart from cohort descriptives, complete cases were used as there were no missing data for variables of interest. AF, atrial fibrillation; BL, baseline; FU follow-up; VKA vitamin K antagonist.

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  Figure 2. ANGPT2, BMP10, and NT-proBNP predict recurrent AF. These three biomarkers were significantly predictive of AF post-ablation after adjustment for randomized treatment and 11 clinical parameters (age, sex, BMI, hypertension, diabetes, chronic obstructive pulmonary disorder, stroke, heart failure, ablation type, ablation energy, and cardioversion during ablation). Unadjusted FGF23 was also predictive of recurrent AF; however, this effect was not present after adjustment. Hazard ratios and corresponding 95% confidence intervals calculated with rank normalized Blom transformed biomarkers using Cox regression. AF, atrial fibrillation; ANGPT2, angiopoietin 2; BMP10, bone morphogenetic protein 10; CA125, cancer antigen 125; ESM1, endothelial cell-specific molecule 1; FABP3, fatty acid–binding protein 3; FGF23, fibroblast growth factor 23; GDF15, growth differentiation factor 15; hsCRP, high-sensitivity C-reactive protein; hsTnT, high-sensitivity cardiac troponin T; IGFBP7, insulin-like growth factor–binding protein 7; IL6, interleukin 6; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

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  Figure 3. Stability of biomolecule concentrations over time. Pre-ablation biomarker concentrations were highly correlated to concentrations of the same biomolecules quantified 3 months after AF ablation, although to varying degrees (A, B), demonstrating the dynamic nature of biomarker measurements post-procedure. Correlations were calculated using original biomarker values with Spearman’s rank correlation. Colour coding (A): Blue indicates positive correlations, pink inverse correlations. Darker shades indicate stronger correlations, lighter shades indicated weaker correlations. ANGPT2, angiopoietin 2; BMP10, bone morphogenetic protein 10; CA125, cancer antigen 125; ESM1, endothelial cell-specific molecule 1; FABP3, fatty acid–binding protein 3; FGF23, fibroblast growth factor 23; GDF15, growth differentiation factor 15; hsCRP, high-sensitivity C-reactive protein; hsTnT, high-sensitivity cardiac troponin T; IGFBP7, insulin-like growth factor–binding protein 7; IL6, interleukin 6; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

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  Figure 4. Reduced ANGPT2, BMP10, FABP3, and NT-proBNP concentrations during follow-up in patients who remain in sinus rhythm. In comparison with pre-ablation concentrations, ANGPT2 (A), BMP10 (B), and NT-proBNP (C) decreased significantly whereas FABP3 (D) increased (all patients, dark blue, left column). When stratified by rhythm outcome, the changes were only noted in the arrhythmia-free group (light blue, middle columns) but not in patients who experienced recurrent episodes (red, rightmost columns). Change difference from 0 calculated using one-sample t-test. Absolute biomolecule concentrations are given in Table 1. ANGPT2, angiopoietin 2; BMP10, bone morphogenetic protein 10; FABP3, fatty acid–binding protein 3; NT-proBNP, N-terminal pro-B-type natriuretic peptide; Rec AF, recurrent atrial fibrillation.

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  Figure 5. Biomolecule-quantified mechanisms of recurrent AF after AF ablation. Our analysis of 12 biomolecules representing different disease processes relevant for AF identify three disease processes associated with recurrent AF after a first AF ablation: altered endothelial shear stress (ANGPT2, orange), altered atrial metabolism (BMP10, blue), and increased cardiac load (NT-proBNP, green). These biomolecules can be used to identify patients at high risk of recurrent AF and provide information on the vascular, atrial, and cardiac processes contributing to recurrent AF. They may also be useful to develop stratified prevention and stratified rhythm control therapy for patients with AF. AF, atrial fibrillation; ANGPT2, Angiopoietin 2; BMP10 bone morphogenetic protein 10; NT-proBNP N_terminal pro-brain natriuretic peptide; HR Hazard Ratio.