Aim      To determine the clinical and prognostic significance of subclinical pulmonary congestion, as evaluated by stress ultrasound (stress-US) examination of the lungs, in the development of heart failure (HF) during the postinfarction period after acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI).

Material and methods  This prospective observational study included 103 patients with no history of HF and with the first AMI and successful PCI. Standard laboratory tests, including the measurement of NT-proBNP, echocardiography, stress-US of the lungs with a 6-min walk test (6MWT), were performed for all patients. Pulmonary congestion was diagnosed with the total number of B lines ≥2 during stress: mild (2-4 B lines), moderate (5-9 B lines), and severe (≥10 В lines). Subclinical pulmonary congestion implied the absence of clinical signs of congestion in the presence of ultrasonic signs of pulmonary congestion (>2 В lines) during stress. The phenomenon of “wet” lung was identified when the total number of B lines was <2 at rest (“dry” lung) and ≥2 after stress. When the total number of B lines was >2 at rest (“wet” lung at rest) and ≥2 after stress, the phenotype was identified as “very wet” lung. The endpoint was hospitalization for HF during 1.5 years.

Results The study showed a high incidence of subclinical pulmonary congestion as determined by the results of stress-US test of the lungs, mild (18.4 %), moderate (37.9 %) and severe (42.7 %), and of “wet” and “very wet” lung phenotypes (65 %). The “wet/very wet” lung phenotypes correlated with the body weight index (R=0.236; p=0.016), troponin concentration upon admission and at 6–12 h (R=0.231; p=0019 and R=0.212; p=0.033, respectively), NT-proBNP concentration (R=0.276; p=0.035), Е peak (R=0.241; p=0.019), global longitudinal strain (GLS) (R=–0.208; p=0.034), and left ventricular end-diastolic dimension (R=0.351; p=0.0004). The higher probability of hospitalization for HF during 1.5 years after the discharge from the hospital correlated with a LV EF ≤48 % (OR, 4.04; 95 % CI: 1.49–10.9; р=0.006), a post-stress total number of B lines ≥10 (OR, 3.10; 95 % CI: 1.06–9.52; р=0.038), a pulmonary artery systolic pressure >27 mm Hg (OR, 3.7; 95 % CI: 1.42–9.61; р=0.007).

Conclusion      Stress-US of the lungs with evaluation of the total number of B lines should be performed for patients after the first AMI and PCI and with no clinical signs of congestion, for stratification of the risk for HF in the postinfarction period.

Aim      To compare variables of transthoracic EchoCG for determining echocardiographic predictors and their prognostic role in the development of persistent paroxysmal ventricular tachyarrhythmias (VT) in patients with ischemic CHF who had been implanted with a cardioverter defibrillator (CD) for primary prevention of sudden cardiac death.

Material and methods  This single-site prospective study included 176 patients with CHF of ischemic origin aged 58.7±7.4 years with a left ventricular ejection fraction (LV EF) of 30 % [25; 34] % who had been implanted with CD. The follow-up duration was 24 months. The primary endpoint was a newly developed persistent paroxysm of VT (duration ≥30 sec) detected in the “monitored” VT area or a VT paroxysm that required electric treatment. The echocardiographic picture was evaluated by 28 variables. Statistical analysis was performed with the c², Fisher’s, and Mann—Whitney tests, and the one-factor logistic regression (LR). Prognostic models were developed with a multifactorial LR. The model accuracy was evaluated by 4 metrics: area under the ROC (AUC), sensitivity, specificity, and diagnostic efficacy.

Results The primary endpoint was observed in 60 (34 %) patients. Mean time to a persistent VT episode was 19.2±0.8 months (95 % confident interval (CI): 17.5–20.8). Superior-inferior dimensions of the right and left atria (RA and LA, respectively) and the left atrial volume (LAv) were independent predictors for VT. The odds of VT development in patients of the study cohort increased with RA_l ≥4.5 cm (odds ratio (OR), 1.6; 95 % CI: 1.4–1.9; р=0.03), LA_l ≥5.5 cm (OR, 2.5; 95 % CI: 1.01–6.1; р=0.04), LAv ≥95 ml (OR, 3.2; 95 % CI: 1.3–17.5; р=0.01). A comprehensive analysis of echocardiographic variables proved the prognostic potential of LAv that was linearly associated with the development of VT. The metrics of the best prognostic model were AUC 0.7±0.07 with 95 % CI: 0.54–0.83; specificity, 20.9 %; sensitivity, 95.7 %; and diagnostic efficacy, 47 %.

Conclusion      This study allowed evaluation of capabilities of transthoracic EchoCG for predicting the probability of VT in patients with CHF of ischemic origin and reduced LV EF. It was shown that linear and volumetric atrial dimensions could be used for stratification of risk of VT and for determining the tactics for primary prevention of sudden cardiac death in this patient category.

Aim      To study the effect of the baseline severity of coronary artery damage according to the SYNTAX scale (baseline score of coronary lesions, BSCL) on the mid-term prognosis in patients with non-ST segment elevation acute myocardial infarction (AMI) (NSTEMI), and to identify the threshold BSCL value that determines high and low risks of adverse cardiac outcomes.

Material and methods  A retrospective analysis was performed for the hospital treatment of patients with NSTEMI (n=421) who had undergone percutaneous coronary intervention (PCI). 256 patients with a repeated hospitalization in mid-term (11.6±3.2 months) were selected for the study. These patients were followed up for the incidence of acute coronary syndrome (ACS), unscheduled repeated myocardial revascularization (URR), and of the composite endpoint (CEP) that included at least one the following events: death, recurrent AMI, unstable angina (UA), and URR. The effect of BSCL on the incidence of these events in mid-term was proven (р<0.05), and then the BSCL threshold value was determined, which allowed segregation of patients into groups of high and low risk of adverse cardiac outcomes.

Results The threshold BSCL value for the risk of ACS was determined as score 14 (odds ratio, OR, 2.79; 95 % confidence interval, CI: 1.32–5.89); for URR and CEP, score 13 (OR, 2.21; 95 % CI: 1.22–4.01 and OR, 2.38; 95 % CI: 1.32–4.31, respectively). Since these threshold values were comparable, for the composite category of events (CEP), the BSCL threshold comprised score 13, and namely this value was taken as a base. According to the multifactorial Cox regression at BSCL score ≥13, the probability of earlier CEP in mid-term was 2.44 times higher than at lower BSCL values (OR, 2.44; 95 % CI: 1.41–4.21; р=0.001). Furthermore, according to the Kaplan-Meier estimate, the effect of BSCL on the survival without adverse cardiac outcomes becomes significant starting from the second half-year (р=0.001, log-rank test).

Conclusion      In NSTEMI patients, the SYNTAX baseline score of coronary lesions >13 is an independent predictor of adverse cardiac outcomes in mid-term starting from the second half-year. Thus, patients with BSCL ≥13 should undergo a follow-up examination no later than at 6 months independent on their clinical condition.

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Aim      To study early manifestations of left ventricular (LV) and right ventricular (RV) myocardial remodeling in high-risk patients.

Material and methods  Intracardiac hemodynamics was studied by equilibrium radionuclide ventriculography (ERVG) in 83 patients (mean age, 61.1±8.9 years) with preserved LV ejection fraction according to echocardiography data, a body weight index (BWI) >25 kg /m², obesity, and type 2 diabetes mellitus (DM2). Parameters of intracardiac hemodynamics were compared in patients with different degrees of obesity and DM2 durations in age groups of younger and older than 60 years.

Results All patients had both LV and RV diastolic dysfunction. The diastolic dysfunction progressed with age and DM2 duration, primarily by the restrictive type. The increase in BWI, in contrast, was associated with increases in ventricular volumetric parameters. It was noted that specifically modifiable risk factors (obesity and DM2), but not the age, mostly facilitated the impairment of RV relaxation.

Conclusion      The strategy of normalizing the body weight and carbohydrate metabolism is priority in combatting the development and progression of chronic heart failure in high-risk group patients.

Aim      To compare results of clinical, laboratory, and genetic examination of patients with familial hypercholesterolemia (FHC).

Material and methods  112 patients aged 40.2±17.9 years (49 men) were examined. The gene of low-density lipoprotein receptor (LDLR) was analyzed and evaluated using the Dutch Lipid Clinic Network (DLCN) criterion of lipid score ≥6. The LDLR gene mutation was searched for using the conformational polymorphism analysis followed by sequencing of the DNA of isolated LDLR gene exons.

Results Mean variables of the blood lipid profile were total cholesterol (C), 10.12±2.32 mmol/l, LDL-C, 7.72±2.3 mmol/l. Corneal arcus was observed in 15 % of patients, tendon xanthomas in 31.8 %, and xanthelasma palpebrarum in 5.3 %. The types of LDLR gene mutations included missense mutations (42.8 %), mutations causing a premature termination of protein synthesis (41.1 %), and frameshift mutations (16.1 %). In the presence of a mutation in exon 4, patients with IHD compared to patients with no IHD had significantly higher levels of total C (10.88±2.08 mmol/l vs. 8.74±1.57 mmol/l, respectively, р=0.001) and LDL-C (8.60±2.14 mmol/l vs. 6.62±1.79 mmol/l, respectively, р=0.005). Patients with IHD compared to patients with no IHD and a mutation in LDLR gene exon 9 had only a higher LDL-C level (8.96±1.53 mmol/l vs. 6.92±1.59 mmol/l, respectively, р=0.022). A differentiated comparison of IHD patients using a logistic regression depending on the identified type of LDLR gene mutation produced formulas for calculating the odds ratio of IHD and myocardial infarction (MI) with adjustments for the patient’s age and baseline LDL.

Conclusion      The detection rate of the LDLR gene mutations was 42.8 % for missense mutations, 41.1 % for mutations causing a premature termination of protein synthesis, and 16.1 % for frameshift mutations. Blood lipid profiles did not differ between patients from different cities and with different types of LDLR gene mutations. Blood lipid profiles were different in IHD patients depending on the mutation type.

Aim    To compare serum concentrations of tryptophane (Trp) and its metabolites in subjects with no cardiovascular disease (CVD) and patients with СVD, including arterial hypertension (AH) and ischemic heart disease (IHD).
Material and methods    This study included 131 participants; 58 participants (11 of them with documented peripheral atherosclerosis) were included into the AH group, 46 participants were included into the IHD group, and 27 participants with no signs of CVD were included into the control group. Plasma concentrations of Trp and its metabolites were measured by high-performance liquid chromatography in combination with a triple quadrupole analyzer.
Results    Comparison of the three study groups revealed significant differences in concentrations of Trp (р=0.029), kynurenine (p<0.001), kynurenine/Trp ratio (p<0.001), quinolinic acid (р=0.007), kynurenic acid (р=0.003), serotonin (p<0.001), and 5‑hydroxyindoleacetic acid (5‑HIAA) (р=0.011). When the AH group was subdivided into subgroups without and with documented peripheral atherosclerosis, the intergroup differences remained for concentrations of kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, serotonin, and 5‑HIAA. Also, correlations were found between concentrations of Trp metabolites and laboratory and instrumental data, primarily inflammatory markers. 
Conclusion    Analysis of serum concentrations of Trp and its metabolites in CVD patients showed increases in kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, and 5‑HIAA along with decreases in concentrations of Trp and serotonin in the groups of AH, AH with documented peripheral atherosclerosis, and IHD.

Aim    To study concentrations of adipokines and their associations with proinflammatory cytokines in overweight men with coronary atherosclerosis. 
Material and methods    This study included 79 men aged 45–60 years with atherosclerosis who had undergone coronary endarterectomy during a coronary bypass surgery, and were overweight (body weight index (BWI), 25.0–29.9 kg /m2). Based on a histological analysis of plaques, the patients were divided into two subgroups: 43 men with stable atherosclerotic plaques and 36 men with unstable plaques in coronary arteries. The control group consisted of 40 age- and BWI-matched men without clinical manifestations of IHD. Blood concentrations of adipokines, including adiponectin, adipsin, lipocalin-2, resistin, and plasminogen 1 activator inhibitor were measured by a multiplex analysis with a MILLIPLEX MAP Human Adipokine Panel 1. Concentrations of proinflammatory cytokines, including tumor necrosis factor α (TNF- α), interleukin (IL)-1β, IL-6, and C-reactive protein (CRP) were measured by enzyme immunoassay. 
Results    The blood concentration of lipocalin -2 was higher in patients with coronary atherosclerosis and stable or unstable atherosclerotic plaques than in the control group (p<0.01). Both subgroups of men with coronary atherosclerosis were characterized by significant differences from the control group in concentrations of TNF-α (p<0.05), CRP, and IL-6 (p<0.01). The most significant direct correlations were found between adipokines and TNF-α, IL-6, and CRP (p<0.01). Results of a logistic regression analysis showed that relative odds for the presence of significant coronary stenoses increased with increasing blood concentrations of lipocalin-2 (OR=1.005, 95 % CI: 1.002–1.008, р=0.011) and IL-6 (OR=1.582 , 95 % CI: 1.241–2.017, р=0.001).
Conclusion    The changes in blood concentrations of adipokines associated with higher levels of proinflammatory cytokines may represent a factor that increases the probability of clinically significant coronary stenosis in overweight men with coronary atherosclerosis.

Aim    To identify possible predictors of tachycardia-induced cardiomyopathy (TICMP) in patients with newly developed decompensated chronic heart failure (CHF) of nonischemic origin with reduced left ventricular ejection fraction (LV EF) and with persistent atrial tachyarrhythmias. 
Material and methods    This study included 88 patients with newly developed decompensated CHF of nonischemic origin with reduced LV EF and persistent atrial tachyarrhythmias. Resting 12-lead electrocardiography (EGC) and transthoracic echocardiography (EchoCG) were performed upon admission and following the electrical impulse therapy for all patients. Also, 24-h ECG monitoring was performed to confirm sinus rhythm stability. After recovery of sinus rhythm, outpatient monitoring was performed for three months, including repeated EchoCG to evaluate the dynamics of heart chamber dimensions and LV EF. 
Results    The patients were divided into two groups based on the increase in LV EF: 68 responders (TICMP patients with a LV EF increase by >10%) and 20 non-responders (patients with an increase in LV EF by <10% during 3 months following the sinus rhythm recovery). According to results of the baseline EchoCG, LV EF did not significantly differ in the two subgroups (TICMP, 40±8.3 %, 18–50 % and non-responders, 38.55±7.9 %, 24–50 %); moreover, the incidence of cases with LV EF <30% did not differ either (9 patients TICMP and 2 non-responders, р=1.0). TICMP patients compared to non-responders, had significantly smaller left atrial dimensions (4.53±1.14 (2–7) cm and 5.68±1.41 (4–8) cm, р=0.034; 80.8±28.9 (27–215) ml and 117.8±41.3 (46–230) ml, р=0.03, respectively) and left ventricular end-systolic volume (ESV) (67.7±33.1 (29–140) ml and 104.5±44.7 (26–172) ml, р=0.02, respectively). The effect of major EchoCG parameters on the probability of TICMP development was assessed by one-factor and multifactor regression analyses with adjustments for age and sex. The probability of TICMP increased with the following baseline EchoCG parameters: end-diastolic volume (EDV) <174 ml [odd ratio (OR), 0.115, 95 % confidence interval (CI): 0.035–0.371], ESV <127 ml [OR, 0.034, 95 % CI: 0.007–0.181], left atrial volume <96 ml [OR, 0.08 , 95 % CI: 0.023–0.274], right ventricular dimension <4 cm [OR, 0.042 , 95 % CI: 0.005–0.389].
Conclusion    Among patients with newly developed decompensation of CHF with reduced LV EF of non-ischemic origin and persistent atrial arrhythmias, TICMP was detected in 72 % of patients. The probability of TICMP did not depend on baseline EF and duration of arrhythmias, but increased with the following baseline EchoCG parameters: EDV< 174 ml, ESV< 127 ml, left atrial volume <96 ml, right ventricular dimension <4 cm. The multifactorial analysis showed that a right atrial volume <96 ml is an independent predictor for the development of TICMP.

Aim    To study the adipokine profile in young people with hypercholesterolemia and low-density lipoproteins (LDL) and to evaluate the relationship between concentrations of LDL cholesterol (LDL-C) and metabolic hormones in men and women younger than 45 years. 
Material and methods    This study included 304 subjects (group 1, 56 men with LDL-C concentration <2.1 mmol/l; group 2, 87 men with LDL-C concentration ≥4.2 mmol/l; group 3, 90 women with LDL-C concentration <2.1 mmol/l; and group 4, 71 women with LDL-C concentration ≥4.2 mmol/l). Serum concentrations of total cholesterol (C), triglycerides (TG), high-density lipoprotein C, and glucose were measured by an enzymatic assay with ThermoFisher Scientific kits and a KonelabPrime 30i biochemical analyzer. LDL-C was calculated using the Friedewald’s formula. Concentrations of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemotactic protein 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor 1 (PAI-1), and resistin were measured by multiplex analysis (Human Metabolic Hormone V3 and Human Adipokine Panel 1 panels).
Results    The groups differed in traditional cardiometabolic risk factors. In the male and female patient groups with LDL-C ≥4.2 mmol/l, the prevalence of impaired fasting glucose, incidence of insulin resistance, TG, and TC were higher than in subjects with LDL-C <2.1 mmol/l. The odds for the presence of LDL hypercholesterolemia (LDL-C ≥4.2 mmol/l) were significantly associated with increased concentrations of C-peptide and lipocalin-2 in men and with increased concentrations of lipocalin-2 and decreased concentrations of GLP-1 in women (р<0.05).
Conclusion    Increased concentrations of LDL-C in young people were associated with changes in the adipokine profile and with the presence of metabolic syndrome components. These results were confirmed by changes in blood concentrations of metabolic markers that characterize disorders of metabolic processes.

Heart failure with reduced left ventricular ejection fraction (LV EF) (HFrEF) is a significant issue of health care due to increasing indexes of morbidity and mortality. The emergence of a number of drugs and implantable devices for the treatment of HFrEF has allowed improvement of patients’ well-being and prognosis. However, high mortality and recurrent decompensated heart failure remain a substantial issue and stimulate the search for new methods of CHF treatment. Cardiac contractility modulation (CCM) is a method of managing patients with HFrEF. Available data from randomized clinical trials (RCT) indicate the efficacy of CCM in improvement of patients’ well-being and quality of life. The question remains open: what effect does CCM have on LV reverse remodeling? Experimental data and results of observational studies suggest a possibility of reverse remodeling by CCM; however, this has not been confirmed in RCT. Also, it remains unclear how CCM influences the frequency of hospitalizations for decompensated heart failure and the death rate of patients with HFrEF. Results of both RCTs and observational studies have shown a moderate improvement of quality of life associated with CCM. Furthermore, RCTs have not found any increase in LV EF due to the therapy, nor has a meta-analysis of RCTs revealed any improvement of the prognosis associated with CCM.  Further RCTs are needed to evaluate the effect of CCM on reverse remodeling, survival rate, and to determine the place of CCM in the treatment of patients with CHF.