Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke. Patients and methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at -70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent. Results: ABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A. Conclusion: Questions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class.

Background: The venous excess ultrasound score (VExUS) is used to objectify systemic venous congestion. The aim of the paper was to determine the association between VExUS grades and worsening renal function (WRF), reduced natriuretic response, diuretics resistance, and mortality in patients with acute heart failure (AHF). Methods: One hundred patients were included, and Doppler ultrasound of hepatic, portal, and renal veins was performed. Severity of congestion was graded using the VExUS score (grade 0, 1, 2, or 3). Sodium concentration in a spot urine sample was assessed in 2 h after the first loop diuretic administration and was adjusted for the prescribed dose of furosemide (31 mmol/40 mg). Diuretics resistance was defined as the need to double the starting dose of intravenous furosemide in 6 h. Results: Patients with VExUS grade 3 showed a higher incidence of WRF (OR: 11.17; 95% CI: 3.86–32.29; p < 0.001) and a decreased natriuretic response: a spot urine sodium content of <50 mmol/L (OR: 21.53; 95% CI: 5.32–87.06; p < 0.001) and an adjusted spot urine sodium content of <31 mmol/40 mg (OR: 9.05; 95% CI: 3.15–25.96; p < 0.001). The risk of diuretic resistance (OR: 15.31; 95% CI: 5.05–46.43; p < 0.001), as well as the need for inotropic and/or vasopressor support (OR: 11.82; 95% CI: 3.59–38.92; p < 0.001), was higher in patients with severe congestion. The hospital mortality rate increased in patients with VExUS grade 3 compared to in patients with other grades (OR: 26.4; 95% CI: 5.29–131.55; p < 0.001). Conclusions: Patients with AHF and VExUS grade 3 showed a higher risk of developing WRF, a decreased diuretic and natriuretic response, a need for inotropic and/or vasopressor support, and a poor prognosis during their hospital stay.

Aims: To evaluate safety and efficacy of moderate intensity interval exercise training early after heart failure decompensation on exercise tolerance and health-related quality of life (HRQoL). Methods and results: This is a prospective randomized controlled study. We screened 234 consecutive patients admitted with decompensated heart failure; 46 patients (42 men/4 women; 61 ± 12 years of age) were randomized to a moderate intensity aerobic interval training ( n = 24) or to a control group ( n = 22). Patients underwent cardiopulmonary exercise testing, echocardiography and Minnesota Living with Heart Failure questionnaire (MLHFQ) at baseline, after three weeks and after three months. After three weeks, peak-VO₂ increased by 17% in the training group ( p = 0.003) with further increase by 10% after three months ( p < 0.001) but did not change significantly in controls. MLHFQ score improved after three weeks, with better results in the training group (from 64.6 ± 15.6 to 30.8 ± 12.9, p < 0.001). After three months, MLHFQ further improved in the exercise training group, but not in controls. Left ventricular ejection fraction was not significantly different between the two groups at baseline and after three months. No serious adverse events related to exercise testing or training were observed. Conclusions: Interval exercise training early after an episode of heart failure decompensation is safe and effective in improving exercise tolerance and health-related quality of life in selected patients after achievement of clinical stability. Positive effects remained sustained after three months. Further studies are needed to define role and indications for interval exercise training early after heart failure decompensation.

Introduction: The dynamics of serum sodium are important in acute heart failure (AHF), and hyponatremia is associated with a poor prognosis. The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on serum sodium concentrations in AHF is unknown. Methods: In a single-centre, controlled, randomized study, patients were prescribed dapagliflozin in addition to standard treatment during the first 24 h of hospitalization versus standard treatments. The pre-specified outcome was an absolute change in plasma sodium concentrations between randomization (first 24 h after admission) and discharge. The secondary outcomes were an absolute change in serum sodium concentrations within 48 h of randomization and the persistence of hyponatremia. Results: The sample comprised 285 patients (53% males; average age 73.26 ± 13 years); 140 of these were randomized to the dapagliflozin group. The average ejection fraction was 46 ± 14%; 155 patients (54%) had ischaemic heart failure; and 35% had diabetes mellitus. Median N-terminal pro b-type natriuretic peptide was 4,225 [2,120; 9,105] pg/mL. The average estimated glomerular filtration rate was 53.9 ± 17.2 mL/min. Hospital mortality was 6.7%. At randomization, serum sodium concentrations were 139.8 ± 4.32 mmol/L in the dapagliflozin group versus 140.85 ± 4.04 mmol/L in the control group; p = 0.048. 48 h later, there was an increase in serum sodium in the dapagliflozin group (2 [−2; 4] mmol/L), as compared to the control group (−1 [−3.75; 2]); p < 0.001. This was accompanied by equilibration of the sodium levels between the groups (141.08 ± 4.08 mmol/L in the dapagliflozin group vs. 140.05 ± 4.82 mmol/L in the control group; p = 0.096). At the time of discharge, there was no difference in serum sodium concentrations (140.98 ± 4.77 mmol/L vs. 139.86 ± 4.45 mmol/L; p = 0.082). The increase in serum sodium concentrations during the period of observation [randomization; discharge] was small but statistically significant in the dapagliflozin group (1 [−3; 3.75] mmol/L vs. −2 [−4.5; 2] mmol/L; p = 0.015). Of 36 patients (21 in the dapagliflozin group and 15 in the control group) with baseline hyponatraemia, this persisted in 6 (16.6%) in the dapagliflozin group and in 11 (73.3%) in the control group (p = 0.008). Conclusion: The use of dapagliflozin in AHF is associated with a tendency to the increase in serum sodium concentrations and lesser persistence of hyponatremia. This effect occurred within the first 48 h and persisted until discharge. The impact of dapagliflozin on serum sodium was more pronounced in patients with hyponatremia at randomization.

Aim To evaluate safety of using rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or transient, stable decline of glomerular filtration rate (GFR) to 15–29 ml /min / 1.73 m2 in the presence of atrial fibrillation (AF). Material and methods This multicenter prospective, randomized study included patients admitted to cardiology departments from 2017 through 2019. Of 10 224 admitted patients 109 (3 %) patients with AF and stage 4 CKD or a stable decline of GFR to 15–29 ml /min / 1.73 m2 were randomized at 2:1 ratio to the rivaroxaban 15 mg /day (n=73) treatment group or to the warfarin treatment group (n=36). The primary endpoint was development of BARC and ISTH major, minor, and clinically relevant minor bleeding. Mean follow-up duration was 18 months. Results Patients receiving warfarin had a significantly higher incidence of BARC (n=26 (72.2 %) vs. n=31 (42.4 %), р<0.01) and ISTH (n=22 (61.1 %) vs. n=27 (36.9 %), p<0.01) minor bleeding and all ISTH clinically relevant (minor clinically relevant and major bleedings) n=10 (27.7 %) vs. n=8 (10.9 %), р=0.03]. The number of repeated hospitalizations was 65 (43% of patients) in the rivaroxaban treatment group and 27 (48% of patients) in the warfarin treatment group (р=0.57), including 24 (36.9 %) and 11 (40.7 %) emergency admissions in the rivaroxaban and warfarin treatment groups, respectively (р=0.96). Significant improvement of changes in creatinine clearance and GFR (by CKD-EPI and Cockroft-Gault) was observed in the rivaroxaban treatment group. Conclusion The study provided evidence for a more beneficial safety profile of rivaroxaban compared to warfarin in patients with AF and advanced CKD.

This review examines the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on different heart failure phenotypes with preserved ejection fraction (HFpEF). Traditional heart failure treatment modalities have shown limited success in improving outcomes for patients with HFpEF, but new evidence suggests that GLP-1RAs could be beneficial. The positive effects of GLP-1RAs are likely due to their ability to reduce systemic inflammation, enhance metabolism and directly affect the cardiovascular system, addressing critical aspects of HFpEF pathology. However, the exact impact of GLP-1RAs on clinical outcomes for different HFpEF phenotypes is still unclear. This review highlights both the potential benefits and the current limitations of GLP-1RA therapy, suggesting a careful approach for their application in clinical practice.