Aim. To study the clinical, morphological and genetic characteristics of young patients with hypertrophic cardiomyopathy (HCM) with indications for primary and secondary prevention of sudden cardiac death (SCD).Material and methods. The study included 44 young patients with HCM who were examined in accordance with national clinical guidelines for HCM (2020). The AHA HCM SCD Calculator was used to calculate the risk of SCD. The genetic study was performed using a target panel of 108 genes associated with cardiomyopathies.Results. In the study cohort, young patients in 72,7% of cases (n=32) had from 1 to 3 cardiometabolic risk factors (on average 1,53±0,8).The age of 18 patients with indications for implantable cardioverter-defibrillator (ICD) ranged from 18 to 44 years (28,8±2,2). The age at diagnosis was 18,5±7,4 years, while the asymptomatic period lasted 6,4±0,9 years. The estimated risk of SCD ranged from 3,11 to 20,71% (6,15 [4,67; 7,32]). In 83,3% of cases (n=15), familial HCM was diagnosed, while 50% (n=9) had a positive family history of SCD. In the subgroup of patients with indications for ICD, genetic variants with pathogenic significance (class IV and V) encoding the production of sarcomere proteins were detected in 6 of 9 probands (66,7%).In patients with indications for ICD (n=18), compared to patients without it (n=26), the diagnosis of HCM was more often established in childhood and adolescence (61,1% vs 23%, p=0,01). In patients with indications for ICD, the reverse curvature hypertrophy of the interventricular septum was significantly more often diagnosed (72,2% vs 38,5%, p=0,028). Among patients with indications for ICD, the proportion of people with low physical activity was 50% (n=9), of which 55,6% (n=5) were diagnosed with overweight/class 1 obesity.Conclusion. Childhood and adolescence at the time of diagnosis of HCM and reverse curvature hypertrophy of the interventricular septum are significantly more common in young patients with indications for ICD.

Among the 42 human amyloidoses described to date the so-called systemic transthyretin amyloidosis, which comprises hereditary forms (more than 140 variants in accordance with the number of identified mutations in the transthyretin gene) and a sporadic form without structural changes in the gene and the protein, is of particular interest. This review summarizes modern understandings of pathogenesis of transthyretin amyloidosis. The symptoms of different forms of transthyretin amyloidosis, issues of early diagnosis, differential diagnosis (including within the group of amyloidoses), advanced therapy and prognosis are considered. Special attention is given to the non-mutant form of transthyretin amyloidosis, the so-called senile amyloidosis, which significantly complicates the course of underlying pathologies in the age group older than 70 years and is still poorly diagnosed. A quite high occurrence of non-mutant form of transthyretin amyloidosis makes it to be considered as a socially significant disease.

Cardiac age-related transthyretin amyloidosis is an underdiagnosed reason of heart failure with preserved ejection fraction, the most frequent form of heart failure. We present a clinical case of detection of transthyretin amyloidosis of the heart at stage I-II of the disease based on biomarkers, which made it possible to send the patient to a third-level hospital and achieve the maximum possible compensation for the disease. Based on this case report, we review modern algorithms allowing to suspect and make the diagnosis, from performing routine tests like ECG and echocardiography to more sophisticated instruments like 2D strain-echocardiography, radiology and endomyocardial biopsy. Also staging systems using biomarkers for cardiac transthyretin amyloidosis are discussed. We consider possible paths to early diagnosis of this disease and nuances of medical therapy.

The objective was to study the clinical features of symptomatic hypertrophic cardiomyopathy (HCM) depending on the age of onset and the presence of cardiometabolic risk factors. Methods and materials. From 2014 to 2020, 250 patients were examined, 100 patients with symptomatic HCM aged 18 to 86 years were included in the study. Results. The incidence of arterial hypertension (AH), obesity, and angina syndrome was significantly higher in patients with HCM aged 45 years and older. The patients with HCM and associated obesity had greater left ventricular end-diastolic dimension and left antero-posterior size regardless of the age of onset of clinical manifestations. The young patients with HCM and associated obesity had more often AH. Patients with HCM with the disease onset ≥ 45 years of age and associated obesity had greater left ventricular posterior wall thickness, left ventricular end-diastolic dimension index. In this group of patients, pulmonary hypertension was more often diagnosed. Conclusion. Obesity and other cardiometabolic risk factors are predictors of the progressive course of HCM, which points the need for their prevention and timely correction.

Relevance. The relevance of the study is determined by the fact that hopes are placed in the cell therapy for patients with critical limb-threatening (CLI) ischemia as a method of the restoration of blood circulation in the affected limb in patients who cannot undergo surgical or endovascular intervention. Aim. To evaluate the efficiency of allogeneic MSCs for the treatment of critical lower limb ischemia (randomized placebo-controlled study).Materials and methods. The study included 34 patients with critical lower limb ischemia (grade 4 according to Pokrovsky). There were 18 patients in the MSC group, and 16 patients in the placebo group). The groups were comparable concerning age, disease duration, and comorbidities. Allogeneic MSCs (phenotype CD73+, CD90+, CD105+, CD45–, CD34–, CD14–) were injected into the posterior calf muscles. Clinical outcome, ankle pressure, transcutaneous oxygen tension (tcpO2), and pain-free walking distance (PFWD) were evaluated. The patients were followed-up for 12–36 months. According to the clinical outcome in each group, the patients were divided into subgroups with «effect (+)» or «effect (–)». In 2 patients, there was an «uncertain clinical outcome». When analyzing the results, these patients were assigned to one or another subgroup.Results. In the MSC and placebo groups, the clinical outcome assessed as «effect (+)» or «effect (–)» did not differ (OR 1.5; 95 % CI 0.34–6.7). With different variants of group formation and with the assignment of patients with an «uncertain clinical outcome» to a one or another subgroup, the final results neither differed. According to instrumental research methods (PFWD, tcpO2, ankle pressure, angiography), there were no differences in the MSC and placebo groups. Conclusion. With different variants of analysis and group formation, no convincing evidence that allogeneic MSCs can be effective for the treatment of critical lower limb ischemia have been obtained.

Russian Society of Cardiology (RSC)With the participation: Russian Association of Cardiovascular SurgeonsEndorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation Task Force: Gabrusenko S.A. (Chairman), Gudkova A.Ya.* (Chairman), Koziolova N.A. (Chairman), Alexandrova S.A., Berseneva M.I., Gordeev M.L., Dzemeshkevich S.L., Zaklyazminskaya E.V., Irtyuga O.B., Kaplunova V.Yu., Kostareva A.A., Krutikov A.N., Malenkov D.A., Novikova T.N., Saidova M.A., Sanakoev M.K., Stukalova O.V.

We report a case of mixed phenotype cardiomyopathy (non-compaction cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy), associated with DSP genetic variant. The sudden cardiac death was the first and only symptom.

Objective. The aim of the work was to evaluate the expression of the MADD gene during the development of myocardial hypertrophy caused by hemodynamic factors in the model of aortic coarctation, as well as in the model of renovascular arterial hypertension (model “2 kidney — 1 clip”). Design and methods. The study involved Wistar rats (n = 60) at the age of 8 weeks. Two experimental models of myocardial hypertrophy were used: the aortic coarctation model (n = 30) and the “2 kidneys — 1 clip” model (n = 21). Animals were divided into groups according to the duration of the experiment (1 and 10 weeks), we also formed a group of intact animals (n = 9). Myocardial hypertrophy was verified by echocardiography. After euthanasia and myocardial extraction, the tissues were homogenized in Extract RNA reagent (Evrogen) in order to obtain RNA. A complementary DNA strand was obtained by reverse transcription using Random (dN) 10-primer (Evrogen) and MMLV RT kit (Evrogen) primers. The relative expression level of the MADD gene in rat myocardium was determined using real-time polymerase chain reaction. The expression level was calculated using the ΔΔCt method; the GAPDH and HPRT genes were used as a reference control. Results. In the aortic coarctation model, MADD gene expression in the 1-week group was significantly higher (p < 0,05) compared with the intact group. In this model, there as a direct correlation of the expression of the MADD gene with NPPA gene, as well as with echocardiography indicators (final systolic size, final diastolic size, and myocardial mass index, p < 0,05), and an inverse relationship between MADD gene expression and the shortening fraction (p < 0,05). The renovascular hypertension model did not show a significant increase in the expression of the MADD gene in myocardium in experimental group compared to intact animals. Conclusions. The expression of the MADD gene increases mainly under the influence of acute hemodynamic overload, and is likely to be important for the immediate response by cardiomyocytes to pressure load. Correlation was found between the expression level of the MADD gene and such echocardiographic parameters as the shortening fraction, end-diastolic and end-systolic sizes of the left ventricle.

Objective. The aim of this study was to investigate gender-specific differences in the clinical profile of hypertrophic cardiomyopathy (HCM) and to determine the impact of polymorphic variant rs1739843 of the HSPB7 gene on clinical profile and outcomes in women and men with HCM. Design and methods . The study population consisted of 171 patients with HCM ≥ 18 years old. A novel disease pathway model was employed to assess clinical course of HCM. Single nucleotide polymorphism (SNP) rs1739843 of the HSPB7 gene was genotyped by allele-specific real-time polymerase chain reaction assay. Results. We found no significant gender-specific differences in clinical course of HCM in patients ≥ 18 years old during 10-year follow-up. High prevalence of T allele of rs1739843 of the HSPB7 gene was observed in women > 18 years old with HCM and chronic heart failure (CHF) with preserved ejection fraction (EF) ( ≥ 50 %) (C: Т , odds ratio (OR) = 0,213, 95 % confidence interval (CI) = 0,077-0,593, p < 0,002). Left atrium (LA) and left ventricle (LV) diastolic diameters were higher and LV diastolic diameter / body surface area was smaller in men than in women with HCM ≥ 18 years old. The frequency of TT genotype of rs1739843 of the HSPB7 gene was greater in men ≥ 18 years old with HCM and CHF III-IV (NYHA) functional class (FC), compared to those with CHF I-II FC (NYHA) (ТТ: ТС + СС, OR = 0,212, 95 % CI = 0,065-0,688, p < 0,03). The allele frequency (С: Т) also differs between HCM male patients with CHF III-IV FC (NYHA), compared to those with CHF I-II FC (NYHA) — 46,9: 53,1 % vs 69,5: 30,5 % (OR = 0,387, 95 % CI = 0,196-0,764, p < 0,006). Men with HCM ≥ 18 years old showed higher T allele frequency in case of HCM progression including those advancing up to CHF III-IV FC (NYHA) and those with CHF III-IV FC (NYHA) + atrial fibrillation. Conclusions. LA and LV diastolic diameters were smaller and LV diastolic diameter / body surface area was higher in women than in men with HCM ≥ 18 years old. There were no significant gender-specific differences in clinical profile of HCM in patients ≥ 18 years old during 10-year follow-up. Allele T of rs1739843 of the HSPB7 gene is associated with HCM and CHF with preserved ejection fraction ( ≥ 50 %) in women ≥ 18 years old. The T allele and TT genotype of rs1739843 of the HSPB7 gene is also associated with HCM and CHF III-IV FC (NYHA) in men > 18 years old.

Aim. To analyze associations of interleukin-6 receptor gene (IL6R) polymorphism (rs2228145) with the clinical course characteristics of hypertrophic cardiomyopathy (HCM) in groups of patients with various cardiometabolic risk factorsMaterial and methods. The sample consisted of 123 patients with HCM. The age of the included patients ranged from 18 to 91 years (59 [41; 66.5]), of whom 59 were men, 64 — women. Two age groups were identified: the first group included patients from 18 to 44 years old, the second — 45 years and older. The control group consisted of 200 people without cardiovascular diseases and other severe comorbidities.For genetic testing, DNA was isolated from peripheral blood lymphocytes. Genotyping of the IL6R gene polymorphism (rs2228145) was carried out by realtime polymerase chain reaction.Results. A significant prevalence of CC genotype of the IL6R gene polymorphism (rs2228145) was revealed in patients aged ³45 years compared with the control group, which occurred in 14,1% and 3,0% of cases, respectively (CC:AC+AA, odds ratio (OR), 0,885, 95% confidence interval (CI), 1,051-0,691, p=0,006), and insignificant prevalence of C allele in this group, which does not reach the level of significance (A:C, OR, 0,870, 95% CI, 0,427-1,02, p=0,06). The prevalence of CC genotype (15,1% vs 3,0%) and C allele (39,0% vs 29,0%) was revealed in patients with HCM in combination with hypertension (HTN) compared with the control group (CC:AS+AA, OR=0,174, 95% CI, 0,047-0,650), p=0,004); (A:C, OR=0,638, 95% CI, 0,406-1,002), p=0,05).Conclusion. The relationship between the IL6R gene polymorphism (rs2228145) and HTN in patients with HCM was confirmed. The presence of CC genotype and C allele of the rs2228145 IL6R gene polymorphism is significantly more common in patients with HCM with the disease onset ³45 years of age. The presence of CC genotype and C allele of the IL6R gene polymorphism (rs2228145) is associated with HTN in patients with HCM.

Background . Today, many studies reflect an increase in the antibacterial effect of drugs through the use of a colloidal solution of silver nanoparticles. Creation of the various forms of drugs for an external use with a slow-release active component and antibacterial activity is relevant and promising for use in the treatment of superficial wounds and injuries. Objective . Synthesis and stabilization of quasispherical silver nanoparticles for external applications. Design and methods . The citrate method was used for the synthesis of colloidal silver. Dosage forms of external use were prepared by several methods: reaction with albumin, liposomal form, thickening with Aerosil and incorporation into microspheres. Results . Several methods of possible preparation of finished dosage forms based on colloidal silver nanoparticles have been demonstrated: reaction with albumin, liposomal form, thickening with Aerosil and incorporation into microspheres. Conclusion . Further investigation of both antimicrobial activity and cytotoxicity will reveal dosage forms with optimal efficiency/safety ratio.

We report a case of mixed phenotype cardiomyopathy (non-compaction cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy), associated with DSP genetic variant. The sudden cardiac death was the first and only symptom.

ВОЗМОЖНОСТИ ПРИМЕНЕНИЯ ГЕМОПОЭТИЧЕСКИХ КЛЕТОК МОНОЦИТАРНОГО РЯДА В ЛЕЧЕНИИ БОЛЬНЫХ КРИТИЧЕСКОЙ ИШЕМИЕЙ НИЖНИХ КОНЕЧНОСТЕЙЗубова Е.С. 1

Aim. To determine the relation between idiopathic hypertrophic cardiomyopathy (HCM) and HCM phenocopies, as well as to study the etiological pattern of HCM phenocopies in patients of the North-Western region of Russia in different age groups.Material and methods. The study included 321 patients with left ventricular hypertrophy ≥15 mm according to an echocardiography. All the necessary clinical, laboratory and instrumental diagnostic methods for verification of HCM and HCM phenocopies was carried out. In the diagnosis, the MOGE(S) classification was used.Results. At a young age, idiopathic HCM accounts for 92% (n=62), HCM phenocopies — 8% (Danon disease (n=1 (2%)), isolated cardiac sarcoidosis (n=1 (2%)) and systemic AL amyloidosis (n=3(4%)). Idiopathic HCM is also found in the vast majority of middle-aged patients — in 85% of cases (n=86). HCM phenocopies (15%) were in isolated cardiac sarcoidosis (n=3 (3%)), systemic amyloidosis variants (n=12 (12%)) — AL amyloidosis with predominant cardiac injury (n=11,11%), hereditary transthyretin amyloidosis (n=1,1%). Of the 153 examined patients with HCM aged ≥60 years old, 85% (n=131) were diagnosed with idiopathic HCM. HCM phenocopies were detected in 15% of cases (n=22). In the etiological pattern of HCM phenocopies, transthyretin amyloidosis was 10%: non-hereditary transthyretin amyloidosis — 6% (n = 9), hereditary transthyretin amyloidosis — 4% (n=6); AL amyloidosis — 4% (n=6). In 1 patient, acromegalic cardiomyopathy (1%) was verified. In this article, we present 3 clinical cases that demonstrate the difficulty of differential diagnosis between idiopathic HCM and various HCM phenocopies.Conclusion. In all age groups, idiopathic HCM predominates. Lysosomal storage diseases classify as rare diseases. Isolated cardiac injury with amyloidosis and sarcoidosis is widely met but less often diagnosed. We determined a high frequency of isolated cardiac injury with amyloidosis under the age of 45 years. The etiological pattern of HCM phenocopies in the elderly is represented mainly by transthyretin cardiomyopathic amyloidosis of hereditary and non-hereditary variants.

Mechanotransduction is an essential mechanism of transforming external mechanical stimulus to biochemical response. In cardiomyocytes mechanotransduction plays an important role in contraction, stretch sensing and homeostasis regulation. One of the major mechanosensitive area in cardiomyocytes, the Z-disk, consists of numbers of structural and signaling proteins, that may undergo conformational or gene expression changes under pathological stress conditions. In present study we examined a rat model of pressure overload cardiac hypertrophy validated by echocardiographic and histopathological examinations. We revealed, that during hypertrophy progression expression of several genes encoding Z-disk proteins (Actn2, Ldb3, Cmya5, Nebl) is different at early and late points of cardiac remodeling. Moreover, expression patterns of several genes are opposite in myocardium of overloaded left ventricle and hemodynamically unaffected right ventricle, and expression profiles in interventricular septum are more similar to right ventricle. Additionally, we revealed inconsistencies between mRNA and protein level changes of Actn2, one of the major structural Z-disk element. All these findings point out, that investigated Z-disk proteins participate in pathological stress adaptation through undergoing the gene expression changes, and suggest the novel important role of hypertrophic response modulation during different stages of cardiac remodeling.

Aim. To study gender differences of clinical course and myocardial remodeling in elderly patients with idiopathic hypertrophic cardiomyopathy (HCM). Material and methods. The study included 131 patients with idiopathic HCM. Patients underwent standard clinical, laboratory and instrumental diagnostics. Results. In the elderly patients with idiopathic HCM, proportion of females was 63% (n=82), males — 37% (n=49). Mean age of females 69±7 y. o., males — 68±7 y. o. Coronary artery disease (CAD) was more common in males (32%) than in females (22%), but with no significant difference (p=0,2). Atrial fibrillation was more common in males (49% vs 29%, respectively, p=0,03). Size of the left atrium and enddiastolic size of the left ventricle in males exceeded those in females (51,2±9,0 mm versus 46,3±4,7 mm, 51,5±7,6 mm versus 45,6±5,7 mm, respectively, p=0,01). In males, symmetrical myocardial remodeling was found more often (42% vs 25%, p=0,04). Obstructive form of HCM was predominant in females (45% and 14%, p=0,01). Chronic heart failure (CHF) with NYHA class III was found in 29% in female group (n=24) and in 12% in male group (n=6), with a tendency to difference (p=0,06). In females, CHF with NYHA class III was mostly due to the left ventricle outflow tract obstruction (n=13) and dilatation phase (n=3). In males, almost all cases of CHF in NYHA class III-IV (8 of 9 patients) were a result of combination of HCM with CAD and previous myocardial infarction. In males, the ejection fraction was significantly lower (55,7±14,8% versus 62,2±10,9%, p=0,01). Conclusion. Proportion of females was higher in elderly patients with idiopathic HCM. Females with HCM were characterized by a more severe course of the disease due to the left ventricle outflow tract obstruction and dilatation phase. In males with idiopathic HCM there were registered more often the following: atrial fibrillation, larger left atrium and end-diastolic size of the left ventricle, symmetrical myocardial remodeling, lower ejection fraction of the left ventricle, — probably associated with a combination of HCM with CAD and previous myocardial infarction.

A literature review presented, with a clinical observation of non-Val30Mettransthyretin amyloid cardiomyopathy. Modern diagnostic and management algorithms discussed.