Aim       To evaluate serum tumor necrosis factor-alpha (TNF-α) levels and determine their prognostic value in patients with stable coronary artery disease (CAD) presenting with either obstructive or non-obstructive coronary artery (CA) lesions.

Material and methods             This prospective, observational, analytical, comparative cohort study enrolled 90 patients aged 40–75 years with stable CAD. Based on the severity of coronary stenosis determined via coronary angiography or multidetector computed tomography angiography, patients were stratified into two groups: those with non-obstructive lesions (ischemia with non-obstructive coronary arteries [INOCA]; n=40) and those with obstructive disease (obstructive CAD [oCAD]; n=50). Baseline levels of TNF-α and vascular endothelial growth factor (VEGF) were quantified using enzyme-linked immunosorbent assay. The follow-up period spanned 24 months. The primary endpoints included mortality, emergency hospitalization for myocardial infarction (MI) or unstable angina, the requirement for elective coronary revascularization, and the incidence of developing chronic heart failure.

Results Females predominated in the INOCA group (n=23, 57.5%), whereas males predominated in the oCAD cohort (n=35, 70.0%; p=0.009). Patients with INOCA exhibited higher levels of total cholesterol (TC; p<0.001), low-density lipoprotein cholesterol (LDL-C; p=0.001), and high-density lipoprotein cholesterol (HDL-C; p=0.002). TNF-α levels were higher in the INOCA group than in the oCAD group (28.17 [14.35–29.79] vs. 12.95 [10.56–22.80] pg/mL; p<0.001). Correlation analysis within the INOCA group revealed a moderate positive correlation between TNF-α and VEGF (ρ=0.332, p=0.045), and weak correlations with TC (ρ=0.284, p=0.094), LDL-C (ρ=0.259, p=0.132), and C-reactive protein (CRP; ρ=0.133, p=0.598). The oCAD group demonstrated a strong correlation between TNF-α and VEGF (ρ=0.724, p<0.001) and a weak correlation with TC (ρ=0.105, p=0.467). ROC curve analysis was performed to evaluate the prognostic utility of TNF-α. The optimal cut-off value calculated via the maximum Youden index was 27.960 pg/mL; a TNF-α concentration above this threshold was predictive of INOCA. This prognostic model yielded a sensitivity of 81.2% and a specificity of 68.6%. Over the 2-year follow-up period, the incidence of adverse outcomes was comparable between the two cohorts. Logistic regression models failed to achieve statistical significance for predicting all clinical outcomes given this sample size and number of recorded cardiovascular complications.

Conclusion       Our findings demonstrate that TNF-α levels are the highest in the INOCA cohort. The ROC curve analysis indicates that TNF-α serves as a statistically significant predictor for the occurrence of non-obstructive CA disease.

Aim       To evaluate the characteristics of cardiac structural and functional changes associated with hyperuricemia (HU) and to examine their relationship with serum uric acid concentrations in patients with chronic kidney disease (CKD).

Material and methods             This single-center cohort study enrolled 507 patients with CKD aged 18–63 years (mean age: 38.3±12.5 years; median: 38 [27; 49] years), comprising 327 (64.5%) males and 180 (35.5%) females. Based on the presence of HU, patients were stratified into two groups: Group 1 (CKD without HU; n = 299) and Group 2 (CKD with HU; n = 208). Clinical, laboratory, and echocardiographic parameters were compared between the two cohorts.

Results               Normal left ventricular (LV) geometry was observed in 316 (62.3%) patients, occurring in 224 (74.9%) of the non-HU CKD group compared to 92 (44.2%) of the HU CKD cohort. LV concentric remodeling (CR) was identified in 39 (7.7%) patients, including 13 (4.3%) without HU and 26 (12.5%) with HU, with CR showing a higher prevalence among males. LV hypertrophy (LVH) was diagnosed in 152 (30.0%) patients: 62 (20.7%) without HU and 90 (43.2%) with HU, with eccentric LVH being the predominant pattern. Regardless of HU status, the overall prevalence of LVH was significantly higher in males. Uric acid concentrations demonstrated a significant positive correlation with age (r=0.189, p<0.05), left atrial anteroposterior diameter (r=0.298, p<0.05), right ventricular longitudinal dimension (r=0.165, p<0.05), LV mass index (r=0.222, p<0.05), relative LV wall thickness index (r=0.206, p<0.05), LV end-systolic dimension (r=0.195, p<0.05), LV end-diastolic dimension (r=0.210, p<0.05), interventricular septal thickness (r=0.210, p<0.05), and LV posterior wall thickness (r=0.228, p<0.05). Conversely, uric acid was negatively correlated with LV ejection fraction (r=–0.166, p<0.05) and estimated GFR (r=–0.323, p<0.05).

Conclusion       In patients with CKD and HU, cardiac morpho-functional alterations are predominantly characterized by concentric remodeling and LV hypertrophy, with the eccentric phenotype being the most prevalent. Elevated uric acid levels in the setting of CKD are associated with cardiac remodeling.

Aim       To evaluate the association between the cumulative burden of risk factors (RFs) for heart failure with preserved ejection fraction (HFpEF) of the left ventricle and its objective instrumental validation using echocardiography (ECHO) and the diastolic stress test (DST).

Material and methods             This study included 291 patients (45.0% males; mean age: 66.0 ± 5.8 years) with arterial hypertension (AH) presenting with dyspnea. All participants had comorbidities/diseases. DST was performed when baseline resting ECHO findings provided insufficient criteria to definitively diagnose HFpEF. The cumulative HFpEF RF burden was quantified as the total score of overlapping comorbidities/interrelated diseases and demographic RFs for HFpEF (female sex and age >65 years). Patients were stratified into two cohorts: Group I (n=139) comprised patients with a high number of RFs (>5 out of 10), and Group II (n=152) included those with a moderate number of RFs (≤5).

Results               Intergroup analysis of major clinical and functional parameters revealed statistically significant differences across multiple characteristics, including the prevalence of HFpEF (62.6% in Group I vs. 39.5% in Group II; p<0.001) and the distance covered in the 6-minute walk test (380.0 [345.0–410.0] vs. 410.0 [389.3–457.0] m, respectively; p<0.001). Notably, patients with HFpEF and a high RF burden exhibited lower exercise tolerance during the DST (59.3% vs. 37.0%; p=0.029). Univariate analysis identified ischemic heart disease (IHD; odds ratio [OR] =2.059, 95% confidence interval [CI]: 1.201–3.351; p=0.009), female sex (OR=2.096, 95% CI: 1.310–3.531; p=0.002), and the HFpEF RF burden (OR=1.471, 95% CI: 1.234–1.753; p<0.001) as the strongest predictors of HFpEF. In the multivariable model, this RF combination retained statistical significance: IHD (OR=1.949, 95% CI: 1.018–3.730; p=0.044), female sex (OR=1.884, 95% CI: 1.052–3.375; p=0.033), and cumulative RF burden (OR=1.258, 95% CI: 1.017–1.558; p=0.035).

Conclusion       Patients with AH and a high HFpEF RF burden exhibit a significantly elevated prevalence of HFpEF confirmed via resting ECHO and DST. The probability of HFpEF is predicted by an increasing RF burden, female sex, and concurrent IHD.

Aim       To evaluate the diagnostic accuracy of an abbreviated transesophageal atrial pacing stress echocardiography (TAPSE) protocol for detecting hemodynamically significant coronary artery stenosis, and to identify the specific patient cohort that derives the greatest diagnostic benefit from this modality.

Material and methods             This study enrolled 364 patients (59.3% males; mean age: 57±9 years) with suspected or established ischemic heart disease (IHD) who underwent both coronary angiography and TAPSE via an abbreviated protocol. Patients were stratified into groups based on the presence or absence of obesity. The diagnostic accuracy of the abbreviated TAPSE protocol for detecting hemodynamically significant coronary artery stenosis was then compared between these groups.

Results               In the overall cohort, the abbreviated TAPSE protocol demonstrated an overall sensitivity of 70%, a specificity of 76%, and a diagnostic accuracy of 75%. Among non-obese patients, this test modification yielded a sensitivity of 69%, a specificity of 81%, and a diagnostic accuracy of 79%. Conversely, in the obese group, the protocol demonstrated a sensitivity, specificity, and diagnostic accuracy of 71%, 72%, and 71%, respectively.

Conclusion       Compared to standard modalities, the TAPSE abbreviated protocol offers a more patient-friendly and well-tolerated profile by significantly reducing total pacing time while maintaining non-inferior diagnostic efficacy for detecting hemodynamically significant coronary artery stenosis. Given its superior specificity in non-obese individuals, this abbreviated TAPSE protocol represents an optimal outpatient screening modality for individuals with suspected IHD who have a normal or overweight body mass.

Aim    To compare biomechanical alterations of the descending thoracic aorta (TA) between segments with and without atherosclerotic plaques (ASPs) of varying severity, and to evaluate the diagnostic utility of the intersegmental aortic wall strain gradient and local wall stiffness.
Material and methods    This study evaluated 182 patients with typical or probable angina using two-dimensional speckle-tracking transesophageal echocardiography to measure the height of each ASP in the descending TA and calculate global peak systolic circumferential strain (GCS, %), pulse pressure (PP)-normalized GCS (GCS/PP), and the aortic β2-stiffness index. Parameters were calculated within plaque-free segments and directly over ASP zones in the descending TA, with differences (∆) in GCS, GCS/PP, and β2 computed between these segments.
Results        Out of 503 identified ASPs from 182 patients, 288 lesions located in the descending TA were evaluated and stratified into two ASP subgroups: 225 (78.2%) with a plaque height <3 mm and 63 (21.8%) with a plaque height ≥3 mm. In the overall pooled ASP cohort, segments with ASPs demonstrated significantly lower GCS and GCS/PP compared to adjacent TA plaque-free segments (3.3 [1.7–4.9] %, 4.6 [2.1–7.1] % vs. 3.8 [2.9–4.8]%, 5.2 [3.8–7.2] %, respectively; p<0.001); however, the β2-index did not differ (18.6 [12.7–26.5] vs. 18.7 [13.5–22.6], respectively; p=0.244). Segments with an ASP height ≥3 mm had lower GCS and GCS/PP than those with a height <3 mm (–3.1 [–3.7; –2.1] %, –3.8 [–5.2; –2.7] vs. 4.0 [2.8;5.4%] %, 5.6 [3.7–7.9], respectively; p<0.001), while displaying a significantly higher β2-index (24.2 [16.4–32.9] vs. 17.1 [12.3–24.3], respectively; p<0.001). No significant differences in GCS, CCS/PP and β2 were found between ASP-free areas and zones with an ASP height <3 mm (p>0.05). Segments with an ASP height ≥3 mm exhibited lower GCS, GCS/PP and β2 values compared to ASP-free zones (–3.1 [–3.7; –2.1] %, –3.8 [–5.2; –2.7], 24.2 [16.4; 32.9] vs. 3.8 [2.9; 4.8] %, 5.2 [3.8; 72], 18.7 [13.5; 22.6], respectively; p<0.001). Correlation analysis established that ASP height was inversely correlated with both GCS (r= –0.55, p<0.001) and GCS/PP (r= –0.58, p<0.001), the total number of ASP-burdened cross-sectional ultrasound segments (r= –0.34, p<0.001 and r= –0.35, p<0.001, respectively), and the count of segments exhibiting negative strain (r= –0.64, p<0.001 and r= –0.59, p<0.001, respectively). Conversely, direct correlations were identified between ∆GCS, ∆GCS/PP, β2, ∆β2 and ASP height (r=0.53, p<0.001; r=0.52, p<0.001; r=0.39, p<0.001; r=0.45, p<0.001, respectively), total cross-sectional ASP-burdened segments (r=0.31, p<0.001; r=0.29, p<0.001; r=0.23, p<0.001; and r=0.28, p<0.001, respectively), and the number of negative strain segments (r=0.57, p<0.001; r=0.57, p<0.001; r=0.20, p<0.01; and r=0.25, p<0.001, respectively).
Conclusion    Multidirectional circumferential strain patterns of the descending TA wall between ASP-free segments and zones with advanced ASPs ≥3 mm induce conflicting inter- and intra-segmental deformation shifts along the aortic wall with an increase in its stiffness, causing a mechanical imbalance during pulse wave propagation and may ultimately create favorable conditions for the development of complicated plaques.

Aim    To evaluate blood pressure (BP) dynamics, target BP (<140/90 mmHg) achievement rates, and safety profiles of fixed-dose hydrochlorothiazide+candesartan and amlodipine+candesartan combinations in outpatients with arterial hypertension (AH).
Material and methods    An open-label, prospective, non-randomized, observational study was conducted across 49 centers in Russia between January 2024 and July 2025. The study enrolled 1,000 patients aged ≥18 years with newly diagnosed AH or a history of AH ≤5 years, who were candesartan-naïve and presented with uncontrolled BP. Upon enrollment, patients were allocated in a 1:1 ratio to receive either a hydrochlorothiazide+candesartan or an amlodipine+candesartan fixed-dose combination. The follow-up period lasted 90 days, with assessment time points at day 14 (based on patient diaries), day 30, and at the end of the study. The primary endpoint was the change in mean BP at day 90 compared to baseline. Secondary endpoints included systolic BP (SBP) and diastolic BP (DBP) dynamics, the proportion of patients achieving BP <140/90 mm Hg, the need for additional therapy, patient adherence, and the incidence of adverse reactions (ARs) at days 30 and 90 of treatment.
Results        A total of 984 patients completed the study (497/500 in the amlodipine+candesartan group and 487/500 in the hydrochlorothiazide+candesartan group), with treatment adherence exceeding 97% in both groups. At Visit 1, the mean BP was 116.0±6.6 mm Hg in the amlodipine+candesartan group (SBP/DBP: 157.3/95.4 mm Hg) and 114.8±6.2 mm Hg in the hydrochlorothiazide+candesartan group (SBP/DBP: 155.2/94.6 mm Hg). After 90 days of treatment, the reduction in mean BP was –21.0±7.9 mm Hg for the amlodipine+candesartan group (–18.1%) and –20.2±7.1 mm Hg for the hydrochlorothiazide+candesartan group (–17.6%); however, the intergroup differences were not statistically significant (p=0.089). By day 90, SBP reductions were –30.8±12.7 mm Hg in the amlodipine+candesartan group and –29.0±11.5 mm Hg in the hydrochlorothiazide+candesartan group. Target BP (<140/90 mm Hg) was achieved by 92.8% of patients in the amlodipine+candesartan group and 92.0% in the hydrochlorothiazide+candesartan group (p=0.473). Five non-serious ARs were reported: 4 in the amlodipine+candesartan group (3 cases of lower extremity edema and one episode of headache) and 1 in the hydrochlorothiazide+candesartan group (one episode of hypotension). The severity of all ARs was mild, requiring neither treatment adjustment nor discontinuation.
Conclusion    Fixed-dose combinations of amlodipine+candesartan and hydrochlorothiazide+candesartan used in the outpatient management of patients with AH provide a clinically meaningful BP reduction, achieving target BP levels in over 92% of cases, while demonstrating a favorable safety profile and high treatment adherence.

Aim    To investigate the association between the serum C-reactive protein (CRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) and microvascular angina (MVA), and to evaluate the potential value of the CHR in identifying patients with MVA.
Material and methods    A total of 70 patients diagnosed with MVA according to the 2018 COVADIS diagnostic criteria based on the absence of functionally significant coronary artery stenoses were enrolled as the MVA group, and 68 patients with no or mild coronary stenosis (<50% on coronary angiography), negative exercise electrocardiography results, and normal coronary blood flow as assessed by corrected TIMI frame count on coronary angiography were included as the control group. Serum concentrations of CRP, HDL-C, and other clinical parameters were measured, and the CHR was calculated. Logistic regression analysis was performed to assess the association between CHR and MVA. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory performance of CHR for MVA.
Results    Serum CHR was significantly higher in patients with MVA than in controls (p<0.001). Logistic regression analysis demonstrated that CHR was independently associated with MVA (OR=2.055, 95% CI: 1.481–2.851, p<0.001). ROC curve analysis showed that CHR exhibited a moderate discriminatory ability for MVA, with an area under the curve of 0.724, a sensitivity of 62.9%, and a specificity of 79.4%.
Conclusion    The CHR might serve as a convenient and cost-effective adjunctive indicator for the preliminary identification of patients with or at increased risk of MVA; however, its role should be regarded as exploratory pending further validation.

Objective    To investigate the predictive value of hypoalbuminemia for diuretic resistance in patients with acute heart failure (AHF) and analyze the associated influencing factors.
Material and methods    A single-center retrospective cohort study was conducted, enrolling 346 patients hospitalized for AHF between January 2021 and January 2025. The patients were stratified into a hypoalbuminemia group (serum albumin <35 g/l, n=121) and a non-hypoalbuminemia group (n=225) based on the initial serum albumin measurement made within 24 hrs of admission. Diuretic resistance was defined as spot urine sodium concentration <50 mmol/l at 2 hrs following the first intravenous loop diuretic administration, or cumulative diuretic efficiency <3 l within 72 hrs of admission with persistent congestive symptoms, or initiation of ultrafiltration therapy within 72 hrs due to inadequate diuretic response. Baseline characteristics, laboratory parameters, echocardiographic findings, and medication data were collected. Binary logistic regression was employed to identify predictive factors for diuretic resistance, and receiver operating characteristic (ROC) curves were constructed to evaluate predictive performance.
Results    Among 346 AHF patients, 118 (34.1%) developed diuretic resistance. The incidence of this resistance was 56.2% in the hypoalbuminemia group versus 22.2% in the non-hypoalbuminemia group (p<0.001). Multivariable logistic regression revealed that serum albumin (p<0.001), eGFR (p=0.002), NYHA functional class IV (p=0.004), and prior heart failure hospitalization (p=0.026) were independent predictors of diuretic resistance. The area under the curve (AUC) for serum albumin in predicting diuretic resistance was 0.812 (95% CI: 0.767–0.857), with an optimal cutoff value of 33.5 g/l, sensitivity of 75.4%, and specificity of 78.9%. The combined prediction model incorporating serum albumin, eGFR, NYHA functional class, and prior heart failure hospitalization achieved an AUC of 0.876 (95% CI: 0.838–0.914), which was significantly higher than that of serum albumin alone (AUC 0.812, 95% CI: 0.767–0.857; DeLong test, Z=3.86, p<0.001).
Conclusion    Hypoalbuminemia serves as an independent predictor of diuretic resistance in patients with AHF. Integration of serum albumin with renal function, cardiac functional classification, and hospitalization history enables effective identification populations at high-risk for diuretic resistance and provides evidence needed for individualized therapeutic strategies.

Objective    To explore the predictive values of serum chloride ion (Cl–) concentration and neurohormonal indicators for diuretic resistance (DR) in patients with heart failure (HF).
Material and methods    A total of 150 patients with chronic HF treated between January 2022 and January 2024 were enrolled. Patients were allocated into a DR group (n=45) and a non-­DR group (n=105) based on their responses to diuretics during hospitalization. Serum Cl–, N-terminal pro­B-type natriuretic peptide (NT-proBNP), plasma renin activity (PRA), norepinephrine (NE), furosemide dosage, and the use of tolvaptan (yes/no) was recorded. Least Absolute Shrinkage and Selection Operator regression analyses was used to screen variables. Logistic regression, Random Forest, and eXtreme Gradient Boosting (XGBoost) models were constructed and evaluated.
Results    DR incidence was 30.0%. Cl– concentrations were significantly lower, whereas NT-proBNP, PRA, and NE were higher in the DR group (p<0.05). Six variables were identified by LASSO regression, including serum Cl–, NT-proBNP, NE, PRA, daily dose of furosemide, and tolvaptan use. All three models demonstrated good predictive performance (AUC values of 0.83, 0.86, and 0.89 for Logistic regression, Random Forest, and XGBoost analyses, respectively). The XGBoost model achieved the highest AUC (0.89), indicating superior discriminative ability, the Random Forest model was slightly better in accuracy and in the machine learning F1 score, whereas the Logistic regression model offered better interpretability. Variable importance analysis revealed that NT-proBNP was the most stable predictor of DR. Low Cl– concentration also exhibited a high predictive value in the Random Forest and XGBoost models.
Conclusion    Indicators of serum Cl– and neurohormonal activation are valuable for predicting DR in HF patients. The XGBoost model outperforms other machine learning models in terms of discriminatory power and potential clinical applications.

Cardio-renal-hepato-metabolic syndrome (CRHMS) integrates arterial hypertension (AH), obesity, insulin resistance, and target organ damage into a single pathophysiological network. This paper sequentially outlines the key pathophysiological mechanisms of CRHMS, including hyperactivation of the renin-angiotensin-aldosterone and sympathetic nervous systems, metainflammation, lipotoxicity, adipokine dysregulation, and endothelial dysfunction, to analyze the clinical features of AH and justify contemporary approaches to its pharmacotherapy. The findings demonstrate that the traditional organocentric approach is frequently ineffective, leaving a high residual risk of cardiovascular complications (CVCs) even when target blood pressure (BP) levels are achieved. The fixed-dose combination of indapamide/perindopril not only ensures stable 24-hour BP control but also reduces the incidence of cardiovascular and renal complications without negatively impacting carbohydrate metabolism. For patients with CRHMS, a personalized organoprotective strategy must be prioritized. The fixed-dose combination of indapamide/perindopril represents an evidence-based, first-line choice that combines high efficacy, metabolic neutrality, and comprehensive target organ protection.