Aim. To determine magnesium deficiency in patients with paroxysmal atrial fibrillation using a comprehensive clinical and laboratory approach. Methods. The prospective cohort study included 35 patients of the cardiology department of the Medical association «Novaya bolnitsa». The main group consisted of 22 patients with frequently recurrent paroxysmal atrial fibrillation, the control group - 13 patients without cardiac arrhythmias. The clinical status, Holter-monitoring of the electrocardiogram, the results of the clinical test for magnesium deficiency, laboratory parameters of calcium, magnesium in blood plasma and formed elements, magnesium in whole blood, free fatty acids and plasma osmolarity were evaluated. Results. The clinical score of magnesium deficiency was significantly higher in patients from the main group compared to the control [16.5 (11÷21) vs 13 (8÷15), p <0.001]. In the main group, there was a decrease of magnesium in the whole blood [0.55 (0.5÷0.59) vs 0.61 (0.58÷0.54), p=0.002] and inside the blood cells [0.68 (0.53÷1.29) vs 1.38 (1.29÷1.44), p <0.001]. In patients with atrial fibrillation there is a shift of the ratio of calcium to magnesium in blood plasma [2.5 (2.5÷3) vs 2.9 (2.8÷3.15), p=0.029] and intracellularly [4.85 (2.62÷9.3) vs 1.7 (1.4÷1.95), p=0.002]. The redistribution of calcium and magnesium is influenced not only by the initial concentration of cations, but also by free fatty acids. The best redistribution was obtained when the concentration of free fatty acids was 900 µmol/l, magnesium 1 mmol/l, and calcium 3 mmol/l, which is consistent with the optimal value of cations in the blood plasma. Conclusion. Patients with paroxysmal atrial fibrillation had a significantly lower magnesium content in whole blood and inside the blood cells; magnesium concentration in the cells and in whole blood closely correlated with the results of the clinical test for evaluating magnesium deficiency; intracellular magnesium content can be influenced by the complexing interaction with free fatty acids.

Aim. To study the characteristics of heart rate variability (HRV) in episodes of paro xysmal atrial fibrillation (AF) and sinus rhythm (SR) during the 24-hour Holter electro cardiographic (ECG) monitoring and to assess the presence and nature of their relationships.Material  and  methods. We analyzed 37 records of 24-hour Holter ECG monitoring obtained from patients with paroxysmal AF. For analysis, records were selected from the Long Term Atrial Fibrillation database (LTAFDB) (n=26), as well as from the long-term storage database “Myocard-holter” of the Sverdlovsk Regional Clinical Hospital № 1 (n=11). Each record contained at least 120 min of SR and at least 120 min of paroxysmal AF episodes. In addition, 48 HRV indices were calculated independently for SR and for AF episodes, after which the 96 HRV parameters obtained for each record were subjected to exploratory data analysis.Results. Analysis of HRV in AF paroxysm showed a significant increase in the RMSSD, SD1, pNN50 indices, which confirmed the great importance of parasympathetic influence in the regulation of AF. Despite the fact that single HRV parameters in AF are not directly related to any single parameters in SR, we have shown that the AF is not completely chaotic and independent of the characteristics of baseline HR variability. We found that for some of the HRV indices determined during AF paroxysm (PAF_CVI, PAF_pNN20, PAF_pNN50, PAF_ApEn, PAF_SDNN, PAF_SD2), up to 74% of the variance of these indices can be explained using multivariate linear models, including 4 HRV indices for SR and taken as predictors. It was shown that among all the indices analyzed, only the PAF_HTI, calculated in paroxysmal AF, had a moderate negative correlation with the duration of AF episodes (r=0,60, p<0,01).Conclusion. It is shown that the study of HRV indices on AF paroxysm has a wide clinical and electrophysiological potential. The paper proposes statistical models that demonstrate the relationship between HRV in SR and in the rhythm of AF episode. The PAF_HTI index, assessed on episodes of AF, showed a relationship with the duration of AF episodes, which suggests the expediency of using HRV characteristics on AF to assess the possibility of SR recovery.

Aim. To analyze heart rate variability of patients with paroxysmal atrial fibrillation and identify electrophysiological phenotypes of the disease by using methods of exploratory analysis of twenty-four-hour electrocardiographic (Holter) recordings. Methods. 64 electrocardiogram recordings of patients with paroxysmal atrial fibrillation were selected from the open Long-Term Atrial Fibrillation Database (repository PhysioNet). 52 indices of heart rhythm variability were calculated for each recording, including new heart rate fragmentation and asymmetry indices proposed in the last 5 years. Data analysis was carried out with machine learning methods: dimensionality reduction with principal component analysis, hierarchical clustering and outlier detection. Feature correlation was checked by the Pearson criterion, the selected patients subgroups were confirmed by using MannWhitney and Student's tests. Results. For the vast majority of patients with paroxysmal atrial fibrillation, heart rate variability can be described by five parameters. Each of these parameters captures a distinct approach in heart rate variability classification: dispersion characteristics of interbeat intervals, frequency characteristics of interbeat intervals, measurements of heart rate fragmentation, indices based on heart rate asymmetry, mean and median of interbeat intervals. Two large phenotypes of the disease were derived based on these parameters: the first phenotype is a vagotonic profile with a significant increase of linear parasympathetic indices and paroxysmal atrial fibrillation lasting longer than 4.5 hours; the second phenotype with increased sympathetic indices, low parasympathetic indices and paroxysms lasting up to 4.5 hours. Conclusion. Our findings indicate the potential of nonlinear analysis in the study of heart rate variability and demonstrate the feasibility of further integration of nonlinear indices for arrhythmia phenotyping.

Aim. To study the effect of proton pump inhibitors (PPIs) on the development of hypomagnesemia in patients with paroxysmal atrial fibrillation (AF) on the background of autonomic sinus node dysfunction (ASND).Material and methods. A prospective cohort study included 32 patients with an established diagnosis of ASND and often recurrent paroxysmal AF. The main group consisted of 17 patients who took pantoprazole at a dose of 20 mg 2 times a day as treatment of diagnosed duodenal erosions within 6 weeks from the time of the initial visit to an arrhythmologist. The remaining 15 patients did not take PPIs and were included in the control group. The determination of magnesium in whole blood, plasma and formed elements was carried out twice in all patients – at the initial visit and after 6 weeks. In addition, in the experiment, complex-forming activity of solutions of various PPIs (esomeprazole, pantoprazole, rabeprazole and omeprazole) with respect to magnesium ions was studied. The author’s method was used, based on turbidimitric determination of the light transmission during the heterogeneous reaction of the formation of magnesium phosphates in the presence of the analyzed drug or without it.Results. There were no significant differences in the magnesium content in the blood of patients of the main and control groups before taking PPIs. After taking of pantoprazole by the patients of the main group there were significant differences between main and control groups in magnesium in whole blood (0.48 [0.44-0.51] mmol/l vs 0.55 [0.5-0.61] mmol/l, p=0.01) and its values in formed elements (0.52 [0.45-0.67] mmol/l vs 0.75 [0.65-1.2] mmol/l, p=0.009). Analysis of magnesium content in patients of the main group before and after taking of pantoprazole also showed a significant decrease in intracellular concentrations of the element (0.6 [0.51-1.0] mmol/l vs 0.52 [0.45-0.67] mmol/l, p=0.002), as well as decrease in its total content in whole blood (0.51 [0.45-0.59] mmol/l vs 0.48 [0.44-0.51] mmol/l, p=0.04). To substantiate the observed effects it was experimentally proved the possibility of formation of strong complex compounds between the ions of magnesium and PPIs: the highest activity was demonstrated by rabeprazole and pantoprazole (coefficients of complex formation per unit of total organic carbon – 1.5 and 0.72, respectively) and the lowest – omeprazole and esomeprazole (0.04 and 0.09, respectively).Conclusion. A decrease of magnesium content in whole blood and formed elements in patients with paroxysmal AF on the background of ADSN was mediated by a six-week intake of pantoprazole in a dose of 20 mg 2 times a day for the treatment of concomitant erosion of the duodenum. When choosing PPIs for arrhythmological patients with concomitant gastro-duodenal pathology, it is advisable to be guided by the complexing activity of drugs with respect to magnesium ions: the most pronounced metal-ligand interaction with magnesium was shown by rabeprazole and pantoprazole, and the least – omeprazole and esomeprazole.