The level of growth differentiation factor 15 as a predictor of left atrial thrombosis in patients with nonvalvular atrial fibrillation.

Aim    To study the role of blood concentration of growth differentiation factor 15 (GDF-15) as a predictor of left atrial/left atrial appendage (LA/LAA) thrombosis in patients with nonvalvular atrial fibrillation (AF).Material and methods    538 patients with nonvalvular AF were admitted to the Tyumen Cardiology Research Center in 2019-2020 for radiofrequency ablation and elective cardioversion. According to findings of transesophageal echocardiography (EcoCG), 42 (7.8%) of these patients had LA/LAA thrombosis and 79 (14.7%) of them had the effect of spontaneous echo contrast (SEC). This comparative, cross-sectional, cohort study included at the initial stage 158 successively hospitalized patients with nonvalvular AF: group 1 (with LA/LAA thrombosis, n=42) and group 2 (without LA/LAA thrombosis and without SEC, n=116). To eliminate significant differences in age between the groups, an additional inclusion criterium was introduced, age from 45 to 75 years. Finally, 144 patients were included into the study: group 1 (with LA/LAA thrombosis, n=42, mean age 60.9±7.2 years) and group 2 (without LA/LAA thrombosis and without SEC, n=116, mean age 59.5±6.0 years). 93 (91%) patients in group 1 and 40 (95%) patients in group 2 had arterial hypertension (p=0.4168); 53 (52%) and 29 (^(%), respectively, had ischemic heart disease (p=0.0611). The groups did not differ in sex, profile of major cardiovascular diseases, or frequency and range of oral anticoagulant treatment. General clinical evaluation, EchoCG, and laboratory tests, including measurements of blood concentrations of GDF-15 and NT-proBNP, were performed.Results    In the group with LA/LAA thrombosis, 1) persistent AF prevailed whereas paroxysmal AF was more frequently observed in patients without thrombosis; 2) a tendency toward more pronounced chronic heart failure was observed; 3) tendencies toward a high median CHA2DS2‑VASc score and toward a greater proportion of patients with scores ≥3 were observed. According to EchoCG findings, group 1 had higher values of sizes and volumes of both atria and the right ventricle, left ventricular (LV) end-systolic volume and size, pulmonary artery systolic blood pressure, and LV myocardial mass index. LV ejection fraction (EF) was in the normal range in both groups but it was significantly lower for patients with LA/LAA thrombosis, 59.1±5.1 and 64.0±7.3, respectively (p=0.00006). Concentrations of GDF-15 (p=0.00025) and NT-proBNP were significantly higher in group 1 than in group 2 (p=0.000001). After determining the threshold values for both biomarkers using the ROC analysis, two independent predictors of LA/LAA thrombosis were obtained by the stepwise multiple regression analysis: GDF-15 >935.0 pg/ml (OR=4.132, 95 % CI 1.305-13.084) and LV EF (OR=0.859, 95 % CI 0.776-0.951). The ROC analysis assessed the model quality as good: AUC=0.776 (p<0.001), sensitivity 78.3 %, specificity 78.3 %.Conclusion    For patients with nonvalvular AF, both increased GDF-15 (>935.0 pg/ml) and LV EF are independent predictors for LA/LAA thrombosis.