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Objective. To determine the blood concentrations of biomarkers of fibrosis and inflammation in patients with metabolic syndrome (MS), atrial fibrillation (AF) and obstructive sleep apnea (OSA) and to establish their role in the formation of left atrial myocardial fibrosis. Design and methods. A cross-sectional case-control study included 286 patients aged 35 to 65 years: 78 patients with MS(+)/AF(+)/OSA(+), 79 patients with MS(+) / AF(+)/OSA(-), 73 patients with MS(+)/AF(-)/OSA(+) and 56 patients with MS(+)/AF(-)/OSA(-). Patients with AF and MS (n = 71) were assessed for the severity of left atrial myocardial fibrosis with electroanatomical mapping. Results. It was found that the concentration of profibrogenic biomarkers circulating in the blood of patients with MS(+)/AF(+)/OSA(+) is higher than in patients with MS(+)/AF(-)/OSA(+): galectin-3 (13,4 (8,5-17,6) and 8,4 (5,1-11,6) pg/ml, p < 0,0001), growth differentiation factor-15 (GDF-15) (1648,3 (775,32568,1) and 856,0 (622,5-1956,4) pg/ml, p < 0,0001), N-terminal peptide of type III procollagen (PIIINP) (95,6 (78,6-120,4) and 50,6 (38,9-68,3) ng/ml, p < 0,0001), N-terminal peptide of type I procollagen (PINP) (3459,4 (2167,1-4112,1) and 2355,3 (1925,0-3382,1) pg/ml, p < 0,0001). In the examined cohort of patients with OSA, positive correlations were found between galectin-3 and cardiotrophin-1 (r = 0,410, p = 0,00002), galectin-3 and GDF-15 (r = 0,430, p = 0,0003), galectin-3 and PIIINP (r = 0,451, p = 0,0001). Correlation analysis showed a strong positive relationship between the apnea/hypopnea index (AHI) and blood concentrations of GDF-15 (r = 0,661, p < 0,00001), galectin-3 (r = 0,519, p < 0,00001), interleukin 6 (r = 0,310, p = 0,0001) and C-reactive protein (CRP) (r = 0,361, p = 0,002). Negative correlations of the average level of SpO2 with CRP (r = -0,354, p = 0,001), galectin-3 (r = -0,451, p < 0,00001), GDF-15 (r = -0,637, p < 0,00001) were found. In patients with AF and OSA, fibrosis was more severe than in patients with AF without OSA (28,6 (23,6-36,6) and 13,5 (9,9-23,6) %, p = 0,0002). AHI positively correlated with the severity of fibrosis (r = 0,708, p < 0,00001). The patients with AF and OSA showed the strongest positive relationship between the severity of fibrosis and PINP (r = 0,572, p < 0,0001; в = 0,511, p < 0,0001) and galectin-3 (r = 0,449, p = 0,0009; в = 0,807, p < 0,0001). Conclusions. An increase in the concentration of fibrosis biomarkers in the blood is associated with an increase in the severity of left atrial myocardial fibrosis and probably has a pathogenetic role in increasing the risk of AF in patients with MS and OSA.

The objective was to study the factors associated with inappropriate reduced doses of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) in real outpatient practice.Methods and materials. 10663 case histories of patients hospitalized to the therapeutic clinic of the university for 5 years (2014 — 2018) were studied, 1307/10663 (12,3 %) case histories of patients with AF were selected. Factors associated with inappropriate low doses of anticoagulant therapy (ACT) with NOACs at prehospital treatment were studied.Results. NOACs received 57.7 % (384/665) of patients with AF at the outpatient stage: rivaroxaban — 180/384 (46.9 %) patients, dabigatran etexilate — 110/384 (28.6 %) patients, apixaban — 94/384 (24.5 %) patients. Inappropriate reduced doses of NOACs were revealed in 68/384 (17.7 %) patients: apixaban — 22/94 (23.4 %), dabigatran — 18/110 (16,4 %) and rivaroxaban — 28/180 (15.6 %) (p>0,05). Patients who received inappropriate reduced doses of NOACs as compared to those who received standard doses of NOACs had higher frequency of major bleedings in the past (7.4 and 1.0 %; p=0.014) and had higher risk of bleedings (HAS-BLED 1.7±1,1 and 1.2±1.0; p = 0.0002). Proportion of patients who had HAS-BLED≥3 in these groups were 19.1 % and 8.6 % (p=0.033). All patients who received inappropriate reduced doses of NOACs had modifiable risk factors of bleedings. 85.3 % of patients with AF who received inappropriate reduced doses of NOACs had high risk of stroke according to CHA2DS2-VASc scale.Conclusion. In real outpatient practice, NOACs were recommended to 57.7 % of patients with AF. 17.7 % of patients received NOACs s in inappropriate reduced doses. Frequency of major bleedings in the past and bleeding risk in AF patients with inappropriate reduced doses was higher than in patients with standard doses.

Aim. To study the frequency of administration of direct oral anticoagulant (DOACs) in doses recommended and not recommended by the instructions of the drugs in non-valve atrial fibrillation (AF) patients.Material and methods. 10663 case histories of patients hospitalized for 5 years (2014-2018) were studied, 1307/10663 (12,3%) case histories of patients with AF were selected. In patients with AF, the risk of stroke and systemic embolism, the risk of bleeding, the anticoagulant therapy (ACT) recommended at the prehospital stage and its adequacy was evaluated.Results. 1 261/1 307 (96,5%) patients had a non-valve AF. The risk of stroke and systemic embolism was 4,7±1,5 (CHA2DS2-VASс), 97,5% of patients with non-valve AF (1229/1261) needed ACT. Only 665/1229 (54.1%) patients with AF received ACT at the time of hospitalization and 578/1229 (47,0%) of patients did not receive ACT. Before hospitalization 281/665 (42,3%) patients received vitamin K antagonist (warfarin). The international normalized ratio in the target range (2,0-3,0) was in 111/281 (39,5%) patients. 57,7% (384/665) outpatients with AF received NOAC: rivaroxaban - 180/384 (46,9%) patients, dabigatran etexilate - 110/384 (28,6%) patients, apixaban - 94/384 (24,5%) patients. Inappropriate reduced doses of DOAC were revealed in 68/384 (17,7%) patients: apixaban - 23,4%, dabigatran - 16,4% and rivaroxaban - 15,6% (p>0,05).Conclusion. In real clinical practice 42,3% AF patients used warfarin, only 39,5% of them had INR in target values. DOAC in inappropriate reduced doses used 17,7% patients.

In this paper, we describe the case of successful surgical treatment of a rare combination of three malignant tumors of the major duodenal papilla in one patient. A 59-year-old woman presented with abdominal pain, fever, nausea, vomiting, weight loss and obstructive jaundice. After routine examination, the patient with suspected cancer of the major duodenal papilla underwent pylorus-sparing pancreatoduodenal resection. Final histology revealed a rare collision of three types of cancer in the major duodenal papilla invading the pancreatic head: moderately-differentiated adenocarcinoma (30 %), moderately differentiated squamous cell carcinoma (20 %) and poorly differentiated small cell neuroendocrine cancer (50 %), surgical resection margins were intact. Immunohistochemical analysis revealed positivity for synaptophysin, chromogranin A and cytokeratin 5/6. The tumor diameter of 2 cm and the absence of signs of locoregional spread allowed the process to be staged as T2N0M0, so the patient did not receive any adjuvant treatment. Follow-up CT performed 6 months later showed two lesions in the liver, and biopsy of one of them was performed. Metastasis of neuroendocrine cancer was histologically and immunohistochemically verified. She started first-line chemotherapy with etoposide + cisplatin.

Respiratory changes caused by obstructive sleep apnea (OSA) syndrome increase the risk of ocular vascular diseases. Hypoxia, hypercapnia, endothelial dysfunction associated with OSA syndrome, promote local impairment of fibrinolysis, cause hypercoagulation and vasospasm, creating conditions for retinal vein occlusions as well as for those of posterior ciliary arteries. 91,5 % patients with retinal vein occlusions and 75 % patients with nonarteritic anterior ischemic optic neuropathy have moderate-to-severe OSA. OSA timely diagnosis and treatment prevent acute vascular pathology of the retina and optic nerve.

Review discusses the problem of non-vitamin K antagonist oral anticoagulants safety in patients with non-valvular atrial fibrillation. Bleeding risk assessment while applying anticoagulant therapy, preventive methods for major bleeding (intracranial, gastro-intestinal) during this therapy as well as the strategy of treating patients with bleedings occurring on direct oral anticoagulants intake are discussed in this review. Special attention is paid to the choice of direct oral anticoagulant, the importance of specific antagonist of dabigatran – idarucizumab and indications for its clinical application.

Aim. To determine the blood concentration of fibrosis biomarkers in patients with atrial fibrillation (AF) in combination with metabolic syndrome (MS) and to analyze the relationship with myocardial fibrosis.Material and methods. This cross-sectional case-control study included 547 patients aged 35 to 65 years: experimental group — patients with MS (n=373), of which 202 patients had AF; comparison group — AF patients without MS (n=110); healthy subjects without cardiovascular diseases and metabolic disorders (n=64). Patients with AF and MS who underwent electroanatomic mapping before pulmonary vein isolation (n=79) were assessed for left atrial (LA) fibrosis severity.Results. It was found that the blood concentration of circulating profibrogenic biomarkers in patients with AF and MS is higher than in patients with AF without MS: aldosterone (135,1 (80,7-224,1) and 90,1 (68,3-120,3) pg/ml, pConclusion. An increase in the blood concentration of profibrogenic biomarkers galectin-3, TGF-beta-1, CTGF, PIIINP, and PINP is associated with an increase in LA fibrosis severity and probably has a pathogenetic role in increasing the AF risk in patients with MS.

The aim of the study was to determine the prevalence of atrial fibrillation (AF) in patients hospitalized in the therapeutic and cardiology departments of the St. Petersburg hospital, and to analyze the prevalence of the number of components of the metabolic syndrome (MS) in patients with AF and anticoagulant therapy (ACT) assigned to outpatient stage to hospitalization. A retrospective analysis of 1760 case histories of patients hospitalized in the therapeutic and cardiology departments of the Therapy Clinic of the Faculty of Pavlov State Medical University named after IP Pavlov for 2017 was performed. It was established that AF was found in 16.5% (286) patients hospitalized in 2017. Among the causes of AF in patients, the number of components of MS was analyzed: 0 – 2.1% (6), 1 – 4.5% (13), 2 – 19.2% (55), 3 – 34.3% (98), 4 – 31.5% (90), 5 – 8.4% (24), thus MS with 3 or more components installed in 74.1% (212) surveyed in 2017. 58.7% (168) received ACT at the time of hospitalization, and 41.3% did not receive it (118). In 32,9% of patients with AF did not receive anticoagulant therapy at the prehospital stage, with no contraindications for administration. Among patients receiving ACT at the time of hospitalization, direct oral anticoagulants were prescribed 2 times more often than warfarin (69% and 31%, р = 0,01).

Aim. To study the incidence of nonvalvular atrial fibrillation (AF) in patients with a CHA2DS2VASc score of 1 in actual clinical practice, to determine the major and minor risk factors of thromboembolism and the frequency of oral anticoagulant therapy in these patients.Material and methods. We performed a retrospective analysis of 6575 medical records of patients hospitalized for five years in a therapeutic inpatient unit. To determine the stroke risk, major and minor modifying factors were assessed.Results. Of 1160 patients with nonvalvular AF, 93 (8,0%) patients had a CHA2DS2VASc score of 1: hypertension (87,1%), heart failure (4,3%), vascular diseases (4,3%), diabetes (2,15%) and age 65-74 years (2,2%); minor modifying factors were as follows: left atrial (LA) dilatation (81,7%), obesity (40,9%), persistent/permanent AF (37,6%), proteinuria (26,9%), chronic kidney disease (3,2%). A combination of minor risk factors was observed in 61,3%, the most common of which were obesity, LA dilatation, persistent/permanent AF. Anticoagulants were prescribed to 72% of patients with a CHA2DS2VASc score of 1.Conclusion. In actual clinical practice, patients with nonvalvular AF with a CHA2DS2VASc score of 1 are often found. The most common risk factors for stroke in these patients are hypertension, persistent or permanent AF, LA dilatation, and obesity. The use of anticoagulant therapy in these patients does not contradict current guidelines. However, further prospective follow-up is necessary to determine the effectiveness and safety of this therapy.

Aim. To evaluate the prominence of fibrosis of the left atrium myocardium and to define the value of transforming growth factor beta 1 (TGF-beta1) and galectin-3 in development of myocardial fibrosis in atrial fibrillation (AF) patients with metabolic syndrome (MS). Material and methods. Totally, 58 patients with AF included, of those 27 with MS. Controls were 50 almost healthy participants. Levels of galectin-3 and TGF-beta1 in blood serum were measured by immune enzyme assay. For fibrosis assessment, the anatomical and amplitude charts of the left atrium (LA) were built up with nonfluoroscopic system of electroanatomical charting CARTO3 (Biosense Webster, USA) and catheter measurement of the contact power with myocardium of LA (Smart Touch Thermocool, Biosense Webster, USA). In “off-line” regimen the evaluation performed of the zones of low voltage in amplitude specters 0,2-0,5 mV and 0,2-1,0 mV with the area measurement by navigation software function “area measurement”. Results. Volume of LA and volume index of LA in AF with MS were higher than in AF with no MS: 78,0±20,4 mL and 60,4±19,8 mL (p=0,005) and 37,8±9,5 mL/m 2 and 30,4±9,0 mL/m 2 (p=0,005), respectively. The percent of LA fibrosis area in AF with MS was higher than in AF with no MS (16,1 [12,8;20,5]% and 10,5 [7,3;16,2]%, respectively, p=0,028). The positive correlations revealed of the level of galectin-3 (r=0,410, р

Atrial fibrillation (AF) is a significant risk factor for stroke and systemic embolism. For prevention of these complications, most AF patients are indicated to take anticoagulants, that reduce the risk cardioembolic strokes, but increase the risk of bleedings, and the most prevalent are gastrointestinal (GIB). Aim. To assess the rate of pathological changes in esophagus, stomach and duodenum, predisposing for GID, in AF patient with higher risk of stroke and absolute indications for anticoagulation therapy. Material and methods. The analysis done, of case histories of hospitalized patients in the therapeutical university clinics, in the year 2016; of those — 263 with non-valvular AF. Among 222 patients with AF and higher risk of stroke, who had indications for anticoagulants, 103 underwent screening fibroesophagogastroduodenoscopy (FEGDS). Results. The FEGDS, performed in 103 patients with non-valvular AF and high risk of stroke, in 45,6% revealed diseases predisposing to GIB, including esophageal cancer — 1 (2,1%), gastric ulcer — 4 (8,5%), duodenal ulcer — 2 (4,3%), erosive esophagitis and reflux disease — 5 (10,6%), varicose veins of esophagus — 4 (8,5%), erosive gastritis — 31 (66,0%) and erosive duodenitis — 3 (6,4%). Combination of diseases was found in 10 (21,3%) patients. Conclusion. Patients with non-valvular AF and high stroke risk, before starting therapy with anticoagulants, it is aimworthy to perform FEGDS for on-time screening for esophageal, gastric, duodenal pathologies predisposing to GIB.

Aim. To determine the blood level of inflammatory markers, parameters characterizing obesity and cardiac remodeling in patients with atrial fibrillation (AF) in combination with metabolic syndrome (MS).Material and methods. This single-stage case-control study included 677 subjects aged 35 to 65 years: patients with MS (n=407), of which 128 patients with AF; comparison group — patients with AF without MS (n=75); control group — practically healthy subjects without cardiovascular diseases and metabolic disorders (n=195).Results. It was found that the blood concentration of circulating pro-inflammatory biomarkers in patients with AF and MS is higher than in patients with AF without MS: C-reactive protein (CRP) (4,43 (2,68-4,98) and 2,33 (1,08-4,7) mg/L, pConclusion. An increase in the blood concentration of proinflammatory biomarkers CRP, IL-6, and TNF-α is associated with cardiac remodeling and epicardial fat thickness in patients with MS and probably has a pathogenetic role in increasing the AF risk in this cohort of patients.

Objective. To evaluate the epicardial fat thickness (EFT) in patients with metabolic syndrome (MS), including paroxysmal and persistent atrial fibrillation (AF). To relate EFT to the fibroid heart marker, i.e. galectin 3. Materials and methods. We examined 100 patients with MS (50 with AF), and 50 healthy persons made the control group. Serum galectin 3 was measured by ELISA method. The EFT was measured with echocardiography. Results. EFT in patients with MS was twofold higher than in healthy persons. EFT in patients with MS and AF didn't differ significantly from that in patients with MS without AF. Positive correlation between the levels of EFT and galectin 3 in serum was revealed. Serum galectin 3 and EFT were associated with atrial fibrillation in patients with MS (OR:1,27, 95% CI 1,02-1,58 and OR:1,73, 95% CI 1,37-2,19, correspondingly).Conclusion. Definition of EFT at echocardiography can be used in the assessment of risk AF in patients with MS.

To evaluate plasma concentration of apelin and its correlation with structural and functional heart parameters in patients with abdominal obesity. 93 patients with abdominal obesity (criteria IDF, 2005) and 21 healthy people at the ages from 25 to 57 years old were investigated. Weight, height, waist circumference, and plasma apelin concentration were measured. Dimensions and volume of the cardiac chambers, systolic and diastolic functions of the ventricles were measured with echocardiographic method. Plasma apelin concentration was higher in patients with abdominal obesity as compared to healthy people (0.70 (0.55 - 0.94) ng/ml and 0.55 (0.42 - 0.72) ng/ml, respectively; p = 0.04). There is significant negative correlation between apelin level and longitudinal size of the left ventricle (r=-0.307; p = 0.003); index of the left atrial volume (r=-0.201; p = 0.05); longitudinal size of the left atrium (r=-0.248; p = 0.02); right atrium volume (r=-0.261; p = 0.01); right atrium area (r=-0,251; p = 0,02); basal size of the right ventricle (r=-0,202; p = 0,05); longitudinal size of the right ventricle (r=-0.234; p = 0.02). Plasma apelin concentration was higher in patients with abdominal obesity as compared to healthy people. There were revealed significant negative correlation between apelin level and longitudinal size of left ventricle, index of left atrial volume, longitudinal size of left atrium, right atrium volume, right atrium area, basal size of right ventricle, and longitudinal size of right ventricle.