Terapevticheskii arkhiv

Aim. To evaluate the features of diagnosis of amyloid cardiomyopathy (ACMP), differential diagnosis of different types of amyloidosis and its clinical manifestations.

Materials and methods. Were analyzed 150 cases of patients who consulted at the Expert Center for Amyloidosis with suspicion of the presence of ACMP. 63 patients were diagnosed with ACMP: 25 (39.7%) – women, 38 (60.3%) – men, with an average age of 64.1±1.5. 36 (57.1%) patients had AL-amyloidosis (immunoglobulin amyloid light-chain amyloidosis), 25 (39.7%) – ATTR-amyloidosis (transthyretin amyloidosis), 2 (3.2%) – AA-amyloidosis with heart failure (reactive systemic amyloidosis caused by hypersecretion of á-globulin). The analysis of clinical manifestations depending on the type of amyloidosis, data of laboratory and instrumental methods of diagnosis is carried out.

Results. In most cases, 53 (84.1%) patients, amyloidosis manifested as signs of heart failure. Among cardiac manifestations, shortness of breath (95.2%), general weakness (93.7%), lower limb edema (76.2%) were the most common. To confirm the diagnosis, despite the high accuracy of the speckle-tracking echocardiography and magnetic resonance imaging of the heart with gadolinium, in rare cases a biopsy is required (e.g. there is a combination of clinical signs of several types of amyloidosis). Biopsy of the affected organ was performed in 31 (49.2%) patients. The strategy for further pathogenetic treatment depends on the determination of the type of amyloidosis. Free light chains of immunoglobulins were detected in 57.1% of cases, which allowed diagnosis of AL-amyloidosis. In 17 (38.6%) patients myocardial scintigraphy with ^99mTc-pyrophosphate showed signs of ATTR-amyloidosis, which with a negative result of immunochemical studies allows non-invasive diagnosis of it.

Conclusion. ACMP is a disease with an extremely adverse prognosis. Raising the awareness of specialists about ACMP is an important goal. With timely diagnosis, pathogenetic therapy can be started early, which will improve the quality of life and prognosis of patients with ACMP.

Aim. To study the association of dynamics of the ejection fraction (EF) of the left ventricle (LV) with the development of adverse cardiovascular events within 12 months after revascularization in patients with chronic heart failure with preserved LV EF (HFpEF), and to determine the value of TNF-related apoptosis-inducing ligand (TRAIL) in predicting changes of LVEF.

Materials and methods. 52 patients with HFpEF hospitalized for coronary artery bypass grafting (CABG) were included in the prospective study. The levels of plasma NTproBNP (before CABG) and TRAIL protein (before CABG and 10 days after CABG) were determined. Echocardiography was performed for these patients at the time of enrollment in the study and after 12 months of follow-up. The patients were divided into 2 groups: group 1 (n=23) included patients with increased LVEF, group 2 (n=29) – with unchanged or reduced LVEF. The development of a combined endpoint (cardiovascular death, decompensated of HF, repeat unplanned revascularization) was studied.

Results. LVEF before CABG was comparable in the studied groups. The frequency of the combined endpoint was 0 in the first group and 17.2% in the second group (p=0.02). There was an inverse correlation between change of LVEF one year after revascularization and the dynamics of the TRAIL protein in the perioperative period (r=-0.45, p=0.049). The area under the ROC for perioperative TRAIL changes and changes in LVEF during a follow-up was 0.79 (95% confidence interval 0.6–0.985; p=0.018).

Conclusion. The increase of LVEF 12 months after CABG in patients with HFpEF is associated with a rarer development of cardiovascular events. The changes of LVEF after CABG can be predicted based on the analysis of the perioperative changes of the TRAIL protein.

Aim. To study the features of macrophages in the tissues of resected valves in operated patients with infective endocarditis (IE), their significance and interaction with inflammatory markers to improve the effectiveness of IE diagnosis.

Materials and methods. Prospectively the research included 25 adult patients with active IE (Duke criteria 2015) and 24 patients with heart defects without IE, hospitalized in a cardiosurgical hospital in Moscow (2021–2022). A standard laboratory and instrumental examination was carried out for the diagnosis of IE, including etiological diagnosis with microbiological and molecular biological methods, and echocardiographic examination of heart. Additionally, the neutrophil-to-lymphocyte ratio (NLR) was calculated. The study of macrophages was carried out in the tissues of resected valves with the determination of the expression of pro- and anti-inflammatory cytokine genes, macrophage markers (CD 68+) using real-time PCR.

Results. Increased expression of proinflammatory cytokines IL-1β, TNF-α and IL-6 was revealed in the group of operated patients with IE with significant differences in IL-1β (CI [IQR] 0.00367 [0.00047–0.01553] vs 0.00018 [0.00012–0.00262]; p<0.05) and IL-6 (CI [IQR] 0.00367 [0.00047–0.01553] vs 0.00018 [0.00012–0.00262]; p<0.05) and IL-6 (CI [IQR] 0.00338 [0.00066–0.01674] vs 0.00054 [0.00044–0.00378]; p<0.05). The expression of anti-inflammatory cytokines in valve tissues prevailed in the control group without significant differences from patients with IE. The macrophage marker CD 68+ was revealed in all examined patients with a significant quantitative predominance in the group of patients with IE. There were no differences in the expression of pro- and anti-inflammatory cytokines depending on the presence of embolic events, intracardiac complications, etiological affiliation to S. aureus, as well as hospital mortality and combined endpoint (death from all causes or recurrence of IE 6 months after surgery) in patients with IE with or without events. Cytokines IL-1β and IL-6 positively correlated with each other, with leukocytes and NLR. ROC analysis determined that IL-1β and NLR had the most favorable features for the diagnosis of IE [IL-1β AUC 0.816 (p=0.02), NLR AUC 0.807 (p=0.03)]. IL-6 did not show a diagnostic value in IE. The threshold value for IL-1β was 0.00029 (sensitivity 86.4%, specificity 60.0%, prognostic value of negative result 75.0% and positive 76.0%, AUC 0.761; p=0.008).

Conclusion. The valve macrophages of patients with IE express elevated levels of proinflammatory cytokines IL-1β and IL-6, regardless of etiological affiliation or complicated course of IE. IL-1β has a high diagnostic value for determining the inflammatory activity in IE.

Background. One of the important links in the pathogenesis of irritable bowel syndrome (IBS) is a change in the composition of the microbiota, and therefore, the use of probiotics in complex therapy can be considered as a pathogenetic treatment of this functional disease.

Aim. To study the effectiveness of probiotic use on the composition of the intestinal microbiota and the dynamics of symptoms in patients with IBS with predominance of diarrhea (IBS-D) or constipation (IBS-C).

Materials and methods. 10 patients with IBS-D and 7 patients with IBS-C who took a probiotic for 28 days, which included: Lactobacillus acidophilus 1.25×10⁹ CFU, Bifidobacterium lactis – 1.25×10⁹ CFU, Lactobacillus paracasei – 1.25×10⁹ CFU, Lactobacillus rhamnosus – 1.25×10⁹ CFU. The dynamics of symptoms was assessed using the Gastrointestinal Symptom Rating Scale, and the composition of the microbiota before and after taking the probiotic was analyzed by sequencing 16S pRNA of stool samples.

Results. In both groups, we found a statistically significant decrease in the level of Proteobacteria and an increase in Firmicutes. In patients with IBS-C, there was a decrease in Negativicutes, which, on the contrary, increased in patients with IBS-D. Shannon's diversity index in patients with IBS-C was statistically significantly lower than in patients with IBS-D 1.55 vs 2.74 (p=0.1). Against the background of the application, there was an increase in microbial diversity in patients with IBS-D, it increased to 3.01, and in patients with IBS-C to 2.68. Against the background of changes in the microbiota, there was a positive dynamics of disease symptoms against the background of taking probiotics.

Conclusion. The results obtained reflect the positive effect of probiotics in patients with IBS-D and IBS-C, which makes it possible to clarify the role of microbiota in the development of IBS and recommend their use as part of complex therapy for this disease.

Aim. Effectiveness and safety of levosalbutamol metered dose inhaler (MDI) in comparison with placebo and salbutamol.

Materials and methods. In this multicenter, randomized, placebo-controlled, 3-period crossover study, all asthma patients (n=91) received levosalbutamol (90 mcg), salbutamol (180 mcg), and placebo using standard MDI. Pulmonary function testing – forced expiratory volume in the first second (FEV₁) and forced vital capacity (FVC) – was performed 45 and 15 minutes before and 5, 10, 15, 30, 60, 90, 120, 180, 240, 300 and 360 minutes after dosing. The primary efficacy endpoint was the baseline-corrected area under FEV₁ curve from 0 to 6 hours (AUC_(0–6h)). Secondary endpoints were the baseline adjusted FEV₁ and FVC peak values, as well as the onset of drug action.

Results. The FEV₁ AUC_{0–6 hours} analysis confirmed similar bronchodilatory levosalbutamol and salbutamol effect (p=0.595), significantly improved compared with placebo (p<0.001). The peak values of FEV₁ and FVC after levosalbutamol or salbutamol dosing were similar (p=0.643) and significantly higher compared with placebo group (p<0.001). The active therapy effect was observed 5 minutes after dosing and throughout the entire observation period up to 6 hours, however, there was some tendency towards a longer duration of action of levosalbutamol compared to salbutamol. Levosalbutamol was well tolerated by patients; after levosalbutamol dosing twiсе fewer adverse reactions were observed compared to salbutamol.

Conclusion. Levosalbutamol at a 90-mcg dose showed efficacy similar to that of salbutamol at a dose of 180 mcg, assosiated with a good safety profile.

Main causes of secondary hypertrophic cardiomyopathy include acromegalic cardiomyopathy. Heart damage in patients with the acromegaly is mediated both by the direct action of growth hormone and insulin-like growth factor-1, and increased deposition of collagen and lymphomononuclear cells in the myocardium, which leads to architectural changes, disturbances in fluid and electrolyte balance, severe left ventricular myocardial hypertrophy, diastolic and systolic left ventricular dysfunction and chronic heart failure. This article presents the world's first described observation demonstrating the possibility of successful transfemoral aortic valve repair to a comorbid patient with severe aortic stenosis according to the potential risks caused by the active form of the acromegaly.

The study of blood flow is becoming a new trend in cardiology and cardiovascular surgery. Based on the literature and our own data, a review is presented on the use of 4D flow in diseases of the heart and blood vessels. The main state of the question about the features of the application of the technique in various pathologies of the cardiovascular system is described in detail, the priorities, limitations and promising directions of the technique application are considered taking into account the goals of practical medicine. The review consists of two parts. The first is devoted to general issues, limitations of the technique, and issues of 4D flow mapping in patients with lesions of the great vessels. In the second part, the emphasis is on the use of 4D flow magnetic resonance imaging in the study of intraventricular blood flow and the application of the technique in congenital heart and vascular diseases.

The article reviews medicinal products for the treatment of iron deficiency conditions and iron deficiency anemia, the prevalence of which is about 30% among the world population. Iron deficiency is a significant cause of anemia, which can lead to hospitalization and even death. In case of intolerance or ineffectiveness of oral formulations of iron supplements, if it is necessary to replenish the iron level quickly, trivalent iron formulations for intravenous administration are used. These supplements are iron complexes with an iron hydroxide core surrounded by a carbohydrate shell. Iron formulations for intravenous administration can be divided into drugs of the "old" and "new" generation. One of the most studied and popular representatives of the "new" generation is iron carboxymaltose (ICM). The results of clinical studies showed that ICM better and faster increases hemoglobin concentration and replenishes iron stores in patients compared to the "old" generation formulations and also has a more favorable safety profile. Large doses of ICM can be administered in a short time, saving resources and increasing patient satisfaction. The injection of large doses of iron with a small number of infusions in the case of ICM is more economically beneficial for all departments of medical institutions, as it significantly reduces the total cost of medical care. Intravenous iron plays an essential role in the perioperative treatment of iron deficiency anemia, especially in elective surgery. Currently, there is a reliable evidence base confirming the efficacy and safety of intravenous iron formulations in chronic kidney disease, inflammatory bowel disease, heart failure, gynecological and obstetric diseases, and cancer.

In September 2023, the European Association for the Study of the Liver (EASL) updated the disease nomenclature for non-alcoholic (metabolically associated) fatty liver disease. The goals of the revision were to increase awareness among health care professionals, civil society and patients about the disease, its course, treatment and outcomes; combating stigma; focusing on the initial etiological factor, including the main (cardiometabolic) risk of disease progression; improved diagnosis based on disease biomarkers; positive impact on the potency to search for new drugs; the ability to provide personalized medical care. The terms “non-alcoholic” and “fatty” were considered stigmatizing, and therefore, it was proposed to use the term steatotic liver disease (SLD) as the name of this nosology. The terms non-alcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD) have been replaced by the term metabolic dysfunction-associated steatotic liver disease (MASLD). In the case of being combined with an alcohol factor, a diagnosis in which metabolic dysfunction is combined with alcoholic liver disease is referred to as MetALD. The fundamental principle in the diagnosis of MASLD is the presence of at least one of the cardiometabolic risk factors. Alcohol consumption interacts with cardiometabolic risk factors and increases the risk of SLD decompensation. The term nonalcoholic steatohepatitis (NASH), according to the new nomenclature, has been replaced by the term metabolic dysfunction-associated steatohepatitis (MASH). The adoption of the new nomenclature should help to increase awareness about the disease, its course and outcomes, as well as improve the quality of diagnosis and treatment.

The article presents the pathographic data of the famous doctor and scientist William Osler. The possible causes of his last illness, the features of the course, diagnostic approaches, and the methods of treatment used in medicine in the early twentieth century are discussed. Ironically, William Osler was a victim of a disease he studied almost all his life, becoming the author of one of his famous aphorisms: "Pneumonia is a friend of old people".