Objective The search for predictors of severe (>35 %) left atrial (LA) fibrosis in patients (pts) with nonvalvular atrial fibrillation (AF) directed for catheter ablation (CA).Materials and Methods 69 pts with nonvalvular AF (57 paroxismal and 12 persistent) aged from 32 to 69 years (mean age 57.1±8.4, 28 females) were included in the study, among them 59 pts (86 %) with arterial hypertension (AH), 24 (34.8 %) – with AH and CAD. Complete physical study, laboratory tests (including NT-proBNP level), comprehensive echocardiography were performed. As a surrogate substrate of LA fibrosis, the area of low-voltage (<0.5 mV) zones in LA was estimated in the process of voltage electroanatomic mapping, as the first stage of CA. The total square of LA fibrosis in absolute values (Sf, cm2) and in percent of total LA square (Sf%), as well as the degree of fibrosis: degree I – <5 %, II – 5–19 %, III – 20–35 %, IV – >35 % were calculated. Degree IV of fibrosis was considered as severe fibrosis.Results Extent of fibrosis didn’t depend on sex, age, body weight, presence of diabetes, CHA2DS2VASc scores, duration of AF history. There was a tendency to smaller Sf in pts with spontaneous termination of AF compared to those who required cardioversion: 7.2 cm2 (4.4; 17.1) and 12.6 cm2 (4.2; 30.5), respectively (p=0.069). Although NT-proBNP level was normal in 62 % of pts (<125 pg / ml), it was higher in Sf% ≥20 % than in Sf% <5 %: 146.0 (48.0; 276.0) and 42.8 (24.2; 91.0) pg / ml, respectively (p=0.0216). The distribution of pts by left ventricular (LV) geometry types was as follows: normal geometry (t.1) – 34, concentric remodeling (t.2) – 16, concentric LV hypertrophy (t.3) – 8, eccentric LV hypertrophy (t.4) – 11. Compared to pts with t. 1 (reference level), pts with t.3 and t.4 had higher LA volume and LV myocardial mass index, and pts with t.4 had larger end-diastolic LV volume and lower LV ejection fraction. Pts with t.4 tended to have higher Sf% than t.1: 31.1 (10.2; 46.2) and 11.2 (5.1; 28.0), respectively (p=0.053). Using logistic regression 3 independent predictors of LA severe fibrosis were detected: type 4 geometry of LV – OR=8.893 (95 % CI 1.150; 68.78), NT-proBNP >128 pg / ml – OR=6.184 (1.01; 37.99), LA volume index >34 ml / m2 – OR=5.92 (1.05; 33.38). According to ROC analysis, the area of the curve AUC = 0.839 (p<0.001), model specificity – 85.1 %, sensitivity – 70.0 %, predictive accuracy – 82.5 %.Conclusion In pts with nonvalvular AF predictors of severe (>35 %) LA fibrosis were LV geometry type in the form of eccentric LV hypertrophy, LA volume index >34 ml / m2 and NT-proBNP >128 pg / ml.
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.
Introduction. Growth Differentiation Factor 15 (GDF-15) is known to be an independent predictor of cardiovascular and all-cause mortality, as well as major bleeding in patients (pts) with non-valvular atrial fibrillation (AF). Since GDF-15 is expressed by a wide array of cells in response to inflammation and myocardial stress, it is interesting to study which clinical and functional parameters are most associated with the level of GDF-15 in pts with non-valvular AF and preserved left ventricular ejection fraction. Aim. To study the relationship of GDF-15 level in blood serum with parameters of clinical and functional status and to determine independent predictors of GDF-15 level in pts with non-valvular AF. Material and methods. 87 pts with non-valvular AF were studied, with an average age of 56.9±9.2 years. A general clinical examination, echocardiography and laboratory tests were performed, including fasting serum glucose (mmol/l),highly sensitive C-reactive protein (h/s CRP) (mg/l), creatinine level (mkmol/l) and subsequent calculation of glomerular filtration rate (ml/min/1.73m2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/ml). The level of GDF15 (pg/ml) in blood serum was determined using an enzyme immunoassay with the help of the human GDF-15/MIC-1 ELISA analytical kit (BioVender, Czech Republic). Results. The increase in the GDF-15 level was associated with ageing, ischemic heart disease, severity of arterial hypertension and heart failure, raising the risk of stroke, according to the scale CHA2DS2-VASc, disturbances of carbohydrate metabolism and obesity, increasing the levels h/s CRP and NT-proBNP, enlargement of the right and left atria, signs of diastolic left ventricular dysfunction and structural remodeling in the form of eccentric hypertrophy. Multiple linear regression analysis revealed 2 independent predictors of GDF-15 levels: age and fasting glucose. Conclusion. GDF-15 appears as an integral biomarker of age-related metabolic disorders and structural and functional changes in the heart, which opens up prospects for further study of its prognostic significance in pts with non-valvular AF.
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