Lower soluble Klotho and higher fibroblast growth factor 23 serum levels are associated with episodes of atrial fibrillation

Aims: The proarrhythmic effect of fibroblast growth factor 23 (FGF23) was observed in patients with end stage kidney disease (ESKD). However, there is no data on the role of FGF23 and soluble Klotho (sKlotho) in the pathogenesis of atrial fibrillation (AF) beyond ESKD. The aim of the study was to assess the peripheral vein and left atrial (LA) serum levels of FGF23 and sKlotho along with calcium-phosphates parameters in patients with AF undergoing percutaneous radiofrequency pulmonary vein isolation (PVI). Methods and results: Sixty-nine consecutive patients (mean age: 55.8 +/- 9.7 years, F/M: 26/43, CHA2DS2-Vasc: 1.7 +/- 1.1) with paroxysmal/persistent AF undergoing PVI were included into the study. Blood samples were taken during PVI baseline from the peripheral vein, then from the LA immediately after a septal puncture. Results: There were significant differences in the concentrations of peripheral and LA serum sKlotho, intact FGF23 (iFGF23), calcium and phosphates; peripheral FGF23, calcium and phosphates levels were significantly higher, and sKlotho levels were significantly lower than the LA concentrations. Serum sKlotho levels correlated with the CHADS2-VASc score (r = 0.254, p = 0.034) and glucose level (r = 0.300, p = 0.005). Serum sKlotho gradient (LA - peripheral vein) correlated with the baseline AF burden in the Holter monitoring (r = -0.389, p = 0.003). PVI efficacy was confirmed in 52 (75%) patients. There was a significant difference in the iFGF23 gradient between patients with AF and without AF (80.3 vs. -47.6 pg/ml, p = 0.009) in the six-month follow-up. A receiver operating characteristic (ROC) analysis revealed that an iFGF23 gradient > 28.7 pg/ml (AUC = 0.742, p = 0.002) was a predictor for AF recurrence. Conclusions: There is a gradient between the LA and peripheral vein in the markers of calcium-phosphate metabolism in patients undergoing PVI. Lower sKlotho and higher iFGF23 serum levels are associated with episodes of AF. Serum iFGF23 gradient is a potent predictor for the recurrence of AF.