Primary Data on ATTR-Amyloidosis Prevalence Among Elderly Patients With Left Ventricular Hypertrophy in Russia.

AIM: To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged >65 years with interventricular septal (IVS) hypertrophy of ≥14 mm. MATERIAL AND METHODS: From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. RESULTS: According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. CONCLUSION: Among patients aged ≥65 years with IVS hypertrophy ≥14 mm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.

Hemodynamic Changes in Intrarenal Blood Flow are Associated With Poor Prognosis in Patients With Acute Decompensated Heart Failure.

AIM: To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF). MATERIAL AND METHODS: This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death. RESULTS: According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p<0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p<0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p<0.001) and had a decreased sodium concentration to less than 50 mmol/l (p<0.001) in a spot urine test obtained one hour after the initiation of furosemide administration. CONCLUSION: Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.

Predictors of tachycardia-induced cardiomyopathy in patients with first-time decompensation of chro-nic heart failure with reduced left ventricular ejection fraction of nonischemic etiology and persistent atrial tachyarrhythmia.

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.

[Guillain-Barre syndrome associated with COVID-19]. / Sindrom Giiena­Barre, assotsiirovannyi s COVID-19.

This paper reports two cases of Guillain-Barre syndrome associated with coronavirus infection COVID-19. The clinical symptoms and neurological status of patients, the data of the additional examination and the features of the prescribed therapy are described in detail. The issue of the tropicity of the SARS-CoV-2 virus to human nervous tissue and its possible ways of affecting the peripheral nervous system is discussed.

Atherosclerosis of the carotid and coronary arteries in elderly patients with acute coronary syndrome.

Aim    To study the relationship between severities of the carotid artery injury and the atherosclerotic process in coronary arteries of elderly patients with acute coronary syndrome (ACS).Material and methods    The study included 110 patients aged >75 years. Based on the degree of maximal carotid stenosis according to data of duplex scanning (DS), all patients were divided into group I, (>50% stenosis) and group II (<50% stenosis).Results    According to coronary angiographic data, multivessel disease was observed in 63.6 % of patients. Patients of group I more frequently had three-vessel coronary artery disease than patients of group II (35.8 and 5.3 %, р<0.001). Coronary angiography and DS showed that 82.7 % patients (in group II, not all carotid stenoses were hemodynamically significant) had a combined damage of coronary and carotid arteries; carotid artery stenoses of >50% were associated with three-vessel coronary artery disease. A correlation between atherosclerosis of carotid and coronary arteries was found. Considering this correlation, a scale was introduced that suggested the severity of coronary atherosclerosis based on DS of carotid arteries. The score was assigned by assessing the degree of maximal stenoses in carotid arteries. A ROC analysis has determined a threshold score suggestive of the severity of coronary atherosclerosis: score <6, absence of >70% coronary stenosis; score >6, likely presence of >70% coronary stenosis (sensitivity, 70 %; specificity, 89 %).Conclusion    Combined coronary and carotid artery disease was detected in 82.7% of elderly patients with ACS. A correlation between the severity of atherosclerosis in carotid and coronary arteries was found. DS of carotid arteries can be extensively used in evaluation of elderly patients with ACS, which will allow additional stratification of patients at high risk of cerebrovascular and recurrent cardiovascular diseases.

RNA Sequencing and Cell Models of Virus-Associated Cancer (Review).

The review summarizes findings from the studies based on the application of technologies for transcriptome analysis to modern cellular model systems of human papillomavirus-associated cancer (HPV) (cervical cancer, head and neck tumors). A diversity of three-dimensional cancer models, such as spheroids, organoids (organotypic cultures), explants, mouse xenografts, are addressed. Particular attention is paid to the use of patient-derived biomaterial for establishing short-term cultures of primary tumor cells, as well as generating multicomponent (heterocellular) systems that comprise, together with the tumor component, other elements of its microenvironment. A number of unique biological properties of HPV-induced neoplasia are discussed, which make generating cell models a unique task. The novel findings in the field of molecular mechanisms of the onset and progression of HPV-associated cancer achieved by using RNA sequencing are presented for each variant of the model systems. These findings are considered in regard to applied aspects of their use, in terms of the opportunities for preclinical testing of new drugs, personalized diagnostics and selection of individual, most effective treatment regimens. The issues of drug resistance development, molecular-cellular heterogeneity, epigenetic reprogramming, and the role of the stromal microenvironment are reviewed. The paper accentuates the problems related to the limitations of the applicability of a particular model system. The areas with a significant lagging behind in omics research of virus-associated cancer in comparison with other types of oncological pathology and possible causes of this lag are noted. The future prospects for the development of model systems of HPV-associated tumors in the field of high-tech tissue engineering, in particular, the use of bioprinting and microfluidic biochips, are also outlined. The combination of these techniques with the methods of whole genome profiling will significantly increase the translational potential of the described model cell systems.

[Tachicardia-induced cardiomyopathy. Case report].

The tachycardia-induced cardiomyopathy is a rare case of reversible heart failure and left ventricle disfunction. The diagnostic approach and treatment strategy are described in this article. Also the clinical case of heart failure compensation in the patient with left ventricle dilatation and atrial flutter after the reverse to sinus rhythm is after catheter ablation presented.

[Characteristics of the Renin-Angiotensin-Aldosterone System in Carriers of Polymorphic Variants of the VDR Gene With Arterial Hypertension and Obesity].

AIM: to study the renin-angiotensin-aldosterone-system (RAAS) in patients with polymorphic variants of the vitamin D receptor gene (VDR), arterial hypertension (AH) and obesity. MATERIALS AND METHODS: We included in this study 98 patients with stage II-III AH and obesity (33 men, 65 women, mean age 61.1±9.9 years and BMI 43.3±5.0 kg/m2). The VDR gene study included genotypes TaqI, BsmI, FokI. After identification of TaqI, BsmI, FokI VDR gene sites we carried out measurements of levels of RAAS markers. RESULTS: We revealed an associative relationship between the presence of allele G of the BsmI site, C/C homozygosity of FokI site of VDR gene and presence of AH in patients with obesity. An increase of renin level was noted only in the homozygous T/T genotype of FokI, no differences in the concentration of aldosterone and angiotensin were detected between any of the studied genotypes. CONCLUSION: Polymorphic alleles and genotypes of the VDR gene can be used as predictors of AH development in obese patients with subsequent characterization of the state of the RAAS system.

[Septic Shock: Innate Molecular Genetic Mechanisms of the Development of Generalized Inflammation].

The capacity for immune surveilance and protection against genetically alien agents is a basic property of multicellular organisms, and increasing significance in realizing this, capacity is assigned to mechanisms of innate immunity. The data accumulated to date show that many components of these mechanisms have a very wide spectrum of biological functions and play essential roles at different stages of ontogeny. An illustrative example is the signal system activated by tumor necrosis factor alpha (TNFα), which is responsible for the inflammation process. Analysis of its structural organization has shown that signaling mechanisms initiating inflammation largely overlap with mechanisms of programmed cell death. This is why hypersecretion of TNFα may lead to systemic inflammatory reation, or septic shok, and, hence, have a fatal outcome. Although studies on the TNFα-dependent mechanism have long history, many aspects of its regulation remain obscure. In particular, this concerns the nature of interspecific differences in the sensitivity of mammals to TNFα action and the ability of TNFα to activate oppositely directed cell programs depending on cell type or ambient conditions. The numerous data obtained in studies on different experimental systems need generalization and critical analysis. This review is an attempt at such an analysis. Its scope is concentrated on modern views on the divergence of TNFα-induced signal at the level of intracellular receptor-associated proteins. A description is given to potential "molecular triggers" responsible for switching between the main TNFα-dependent signaling pathways: inflammation, apoptosis, and necroptosis. The contribution of necroptosis (genetically programmed necrotic cell death) to the development of systemic inflammation and the lethal effect of TNFα are described. Consideration is also given to various lines of mice possessing natural resistance or sensitivity to TNFα, which hold much promise as models for deciphering the molecular genetic bases of the regulation of innate immune reactions and other TNFα-dependent processes.

[Low calorie diet influence optimization on body composition at obese patients with secondary diastolic heart failure].

In open prospective monocentric study in 3 parallel groups we studied the effectiveness of correction of body composition using low calorie diet therapy with inclusion of specialized food products (SFP)--sources of polyphenols and iridoids made on the basis of the juice of Morinda citrifolia L. fruits. We studied 90 patients aged from 30 to 50 years old with grade III obesity and clinically expressed secondary diastolic heart failure. The duration of diet therapy was 42 days. It was shown that low-calorie diet has non-optimal effect on the body composition in morbidly obese patients with secondary diastolic heart failure, namely leading to the expressed loss of body fatless (7.2%, p=0.00008) and muscle mass (by 16.6%, p=0.00004); at the same time the reduction of total body weight is noted only by 2.3% (p=0.053), reduction of waist measurement by 1.3% (p=0.028) and reduction of hips measurement by 1.3% (p=0.09), accompanied by the reduction of body fat by 8.5% (p=0.000017) and of liquid by 7.3% (p=0.0018). The introduction of the SFP into the diet optimizes the effect of low calorie diet therapy on the anthropometric parameters and body composition. The most important effect of the SFP is the ability to prevent the excess loss of muscle mass in patients, and this effect is being dose-dependent. The loss of muscle mass in two groups of patients was 3.1-4.1% after 6 weeks of diet therapy, while in the control group it was 8.5% (p=0.0051). We have concluded that the inclusion of the SFP, manufactured on the basis Morinda citrifolia L. (noni) juice to the low calorie diet allows to initiate mainly the loss of the body fat with the simultaneous protection of active cellular mass, which is without doubt can be considered as the advantage compared to the standard low calorie diet.

[Morphologic and histochemical changes in atrial and ventricular myocardium following adrenaline damage]. / Morfologicheskie i gistokhimicheskie izmeneniia miokarda zheludochkov i predserdii pri adrenalinovom povrezhdenii.

Changes in the myocardium developing after a single injection of toxic doses of adrenaline were studied. The course of adrenaline damage of the myocardium was shown to be wave-like. The most massive areas of degeneration and necrosis were observed on the 7th--14th day of the experiment. Ischemia developing because of the change of the microcirculation bed and impaired hemodynamics in the myocardium is a very important factor in the pathogenesis of adrenaline damage. The development of degeneration and necrotic areas in the auricles was found to occur later than in the ventricles which may be due to the ultrastructural features of atrial cardiomyocytes: the presence of electron dense granules, the destruction and decrease in the number of which coincide with the most marked signs of the heart muscle injury.