Fibroblast Growth Factor 23 in atrial fibrillation: Effects on atrial structure and function

• Applicant: Professor Dr. Paulus Kirchhof
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564997921

Understanding the causes of atrial fibrillation (AF) and AF-related complications in patients can improve prevention, risk prediction, therapy, and outcomes of this common disease. Circulating biomolecules provide quantitative proxies for disease mechanisms. Their use in patients with AF relies on an understanding of their effects in the atria. Fibroblast growth factor 23 (FGF23) was recently identified as a biomolecule associated with AF and with AF-related complications. Experimental pilot data suggest acute arrhythmogenic effects of FGF23 on cardiomyocytes and longer-term effects of FGF23 on atrial structure and fibrosis mediated via activation of cardiac fibroblasts. A developmental interaction of FGF23 and PITX2 and clinical data suggest that FGF23 interacts with the genomic basis for AF. To enable the use of FGF23 as a biomolecule in patients with AF, this project will determine the effects of FGF23 on atrial structure and function using mouse atria and patient data. In aim 1, the acute and chronic effects of FGF23 on function and structure will be determined in mouse atria using atrial electrophysiology, histology, and molecular biology techniques. The experimental part will study mouse atria with normal and reduced PITX2 concentrations to determine the interaction between FGF23 and PITX2. In aim 2, detailed atrial imaging and mapping data from patients undergoing AF ablation will be analyzed. Open-source software developed for analysis of atrial mapping data and state-of-the-art strain imaging of the atria will be combined to quantify atrial structure and function in patients. These detailed phenotypes will be related to FGF23 concentrations. In aim 3, rhythm outcomes and cardiovascular events will be related to FGF23 concentrations in clinical data sets integrating detailed phenotypes and additional cardiovascular biomolecules with detailed rhythm follow-up and with long-term capture of cardiovascular events (3-5 years follow-up time). All experimental models and setups for functional and structural assessment, clinical data sets, biomolecule concentrations, infrastructure and expertise for analysis of the data and advanced statistical methods are available for the project. The combination of methods will enable characterization of the effects of FGF23 on atrial function and structure, replicate the findings in patient atria, and determine associations with AF-related complications in patient data sets. Thereby, the project will determine the effects of FGF23 on atrial structure and function and determine its ability to predict recurrent AF and cardiovascular events, enabling its use as an atrial biomolecule for diagnosis, risk estimation, and for development of new therapeutic strategies in patients with AF.

• DFG Programme: Research Grants