The association of growth differentiation factor 15 (GDF-15) level with extent of left atrial fibrosis in patients with nonvalvular atrial fibrillation

Abstract

Aim To study the relationship between the serum level of growth differentiation factor 15 (GDF-15) and clinical and functional characteristics and severity of left atrial (LA) fibrosis in patients with nonvalvular atrial fibrillation (AF).Material and methods The study included 87 patients with nonvalvular AF (62 patients with paroxysmal AF and 25 patients with persistent AF) aged 27 to 72 years (mean age, 56.9±9.2 years, 32 women). 85 % of these patients had arterial hypertension (AH), 33 % had AH and ischemic heart disease, and 12.6 % had isolated AF and were hospitalized for primary catheter ablation. General clinical evaluation, echocardiography, laboratory tests including measurement of GDF-15 and NT-proBNP concentrations in blood were performed. As a surrogate substrate of LA fibrosis during the electroanatomical voltage mapping, the area of low-voltage (<0.5 mV) zones in LA was calculated, including the total LA fibrosis area (Sf, cm2) and a percentage of fibrosis of the total LA area (Sf%).Results Median concentration of GDF-15 was 767.5 [590.0; 951.0] pg /ml. The GDF-15 level positively correlated with age, presence and severity of AH and chronic heart failure, body mass index, and degree of obesity, CHA2DS2 VASc score, level of NT-proBNP, and LA fibrosis area (Sf and Sf%) and negatively correlated with the indexes of left ventricular diastolic function, e' septal and e' lateral. The area of fibrosis increased with increasing GDF-15 concentrations divided into quartiles; Sf% exceeded 20 % at GDF-15 levels higher than median. After a comparative analysis of patients with Sf% ≤20 % and >20 %, statistically significantly different variables were included into a stepwise logistic regression analysis. Two independent predictors of LA fibrosis >20% were identified: a concentration of GDF-15 higher than median (odd ratio (OR), 3.318, 95 % confidence interval (CI): 1.184-9.298) and LA volume index (OR, 1.079, 95 % CI: 1.014-1.147). According to results of the ROC analysis, the area under the curve (AUC) was 0.762 (p=0.000), the model specificity was 72.3 %, sensitivity was 72.4 %, and the prediction accuracy was 72.4 %.Conclusion Blood levels of GDF-15 were associated with the presence and severity of major risk factors for AF and the area of LA fibrosis. In this study, a level of GDF-15 above the median and the LA volume index were independent predictors of LA fibrosis > 20% of the LA area.