The dynamics of cardiac signals can be studied using methods for nonlinear analysis of heart rate variability (HRV). The methods that are used in the article to investigate the fractal, multifractal and informational characteristics of the intervals between heartbeats (RR time intervals) are: Rescaled Range, Detrended Fluctuation Analysis, Multifractal Detrended Fluctuation Analysis, Poincaré plot, Approximate Entropy and Sample Entropy. Two groups of people were studied: 25 healthy subjects (15 men, 10 women, mean age: 56.3 years) and 25 patients with arrhythmia (13 men, 12 women, mean age: 58.7 years). The results of the application of the methods for nonlinear analysis of HRV in the two groups of people studied are shown as mean ± std. The effectiveness of the methods was evaluated by t-test and the parameter Area Under the Curve (AUC) from the Receiver Operator Curve (ROC) characteristics. The studied 11 parameters have statistical significance (p < 0.05); therefore, they can be used to distinguish between healthy and unhealthy subjects. It was established by applying the ROC analysis that the parameters H_q=2(MFDFA), F(α)(MFDFA) and SD₂(Poincaré plot) have a good diagnostic value; H(R/S), α₁(DFA), SD₁/SD₂(Poincaré plot), ApEn and SampEn have a very good score; α₂(DFA), α_all(DFA) and SD₁(Poincaré plot) have an excellent diagnostic score. In conclusion, the methods used for nonlinear analysis of HRV have been evaluated as effective, and with their help, new perspectives are opened in the diagnosis of cardiovascular diseases.

Paroxysmal Atrial Fibrillation: Insight Into the Intimate Mechanisms of Coagulation

Early Changes in the Antithrombin and Thrombin-Antithrombin Complex in Patients With Paroxysmal Atrial Fibrillation

Introduction: Paroxysmal atrial fibrillation (PAF) is a well-documented prothrombotic state that carries significant embolic risk. However, precise hemostatic changes in the very early stage of the disease are not completely studied. The aim of the study was to study von Willebrand factor (vWF) and coagulation factor VIII (FVIII) plasma levels and activity in the first hours (up to 24 h) of PAF clinical manifestation.Material and methods: We selected consecutively 51 non-anticoagulated patients (26 men, 25 women, mean age: 59.84 ±1.60) with PAF and 52 controls (26 men, 26 women, mean age: 59.50 ±1.46 years) corresponding in gender, accompanying diseases and conducted treatment. The indicators were examined using enzyme-linked immunoassays and photometric tests.Results: All patients were hospitalized between the 2nd and 24th h after the onset of arrhythmia (mean: 8.14 ±0.74 h). Higher FVIII levels (107.52 ±3.48% vs. 93.85 ±2.93%, p < 0.05) and activity (200.03 ±11.11% vs. 109.73 ±4.90%, p < 0.001) were found in the PAF group. vWF levels (178.40 ±12.95% vs. 119.53 ±6.12%, p < 0.001) and activity (200.92 ±12.45% vs. 110.80 ±5.14%, p < 0.001) were also higher. These changes did not depend on age, sex, body mass index or CHA2DS2-VASc score in the PAF group (p > 0.05). PAF duration was a significant predictor of increased FVIII levels and activity. Increased PAF duration was followed by increased values of the factors (r = 0.85, p < 0.001; r = 0.83, p < 0.001).Conclusions: The results presented an activated coagulation cascade and endothelial injury, suggesting hypercoagulability still in the early hours of PAF. These changes in PAF did not correlate with CHA2DS2-VASc score risk factors, outlining PAF as a possible independent embolic risk factor.

Increased coagulation activity has been established in paroxysmal atrial fibrillation (PAF), but data on the anticoagulant system are scarce. To examine the protein C anticoagulant pathway in the early hours of the disease. Fifty-one patients (26 men and 25 women; mean age 59.84 ± 1.60 years) and 52 controls (26 men and 26 women; mean age 59.50 ± 1.46 years) were selected for the study. Protein C antigen and its activity, total protein S, free protein S and its activity, soluble forms of endothelial protein C receptor (sEPCR), and thrombomodulin (sTM) were examined in the plasma. The indicators were studied in patients between the 2nd and the 24th hour after the onset of arrhythmia. Levels of protein C were significantly elevated in patients compared to controls (111.40% ± 6.66% vs 94.83% ± 4.47%; P = .039). Protein C activity showed significant reduction in PAF (73.13% ± 5.80% vs 103.3% ± 3.80%; P < .001). Total protein S levels did not differ significantly (108.20% ± 4.07% vs 102.40% ± 3.65%; P = .30). Free protein S (76.81% ± 6.01% vs 122.10% ± 3.97%; P < .001) and its activity (71.39% ± 6.27% vs 119.50% ± 6.54%; P < .001) were reduced in patients. Higher levels of sEPCR (203.10 ± 10.33 vs 133.10 ± 7.37 ng/mL; P < .001) and sTM (6.50±0.40 vs 4.48±0.28 ng/mL; P < .001) were measured in PAF. Protein C activity is reduced still in the first hours (until the 24th hour) of PAF clinical manifestation, determining reduced activity of the anticoagulant pathway as a whole. The established low levels of free protein S and its activity as well as low sEPCR and sTM levels are a possible explanation of the changes in protein C activity.

There are no studies to date on the early changes in the hemostasis profile of patients with paroxysmal atrial fibrillation (PAF). Given the key role of the fibrinolytic system in maintaining blood fluidity, our aim was to examine its activity in patients with clinical manifestation of the disease <24 hours. We studied 51 nonanticoagulated patients with a first episode of the disease (26 men, 25 women; mean age 59.84 ± 1.60 years) and 52 controls (26 men, 26 women; mean age 59.50 ± 1.46 years) who matched the patients in terms of gender, age, comorbidities, and conducted treatment. Using enzyme-linked immunoassays and colorimetric assays we assessed the plasminogen activity, tissue plasminogen activator level (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), α2-antiplasmin activity (α2-AP), D-dimer level, and vitronectin level. Blood samples were collected immediately after hospitalization. Patients were hospitalized between the second and twenty fourth hours (mean 8.14 ± 0.76 hours) after the onset of PAF. Compared to controls, plasminogen (159.40 ± 4.81 vs 100.2 ± 2.88%, P < 0.001) and t-PA levels (11.25 ± 0.35 vs 6.05 ± 0.31 ng/mL, P < 0.001) were significantly higher in the patient group. PAI-1 activity (7.33 ± 0.37 vs 15.15 ± 0.52 AU/mL, P < 0.001) and α2-AP (112.9 ± 2.80 vs 125.60 ± 3.74%, P < 0.05) as well as vitronectin plasma levels (134.7 ± 5.83 vs 287.3 ± 10.44 mcg/mL, P < 0.001) were lower in the PAF group. Conversely, the levels of D-dimer in patients were significantly higher (0.53 ± 0.07 vs 0.33 ± 0.02 ng/mL, P < 0.05). Early changes in the fibrinolytic system occur in PAF, suggesting their close relationship with the manifestation of the disease. There is high plasma fibrinolytic activity, during the very first 24 hours of the disease, which is most likely a pathophysiological response to the intensified procoagulation process.