Aim. To evaluate the effect of angiotensin II receptor blocker (ARB) therapy on the expression of transforming growth factor-β (TGF-β) in the myxomatous mitral valve, on the serum levels of TGF-β1/TGF-β2 and the left ventricular (LV) systolic function in patients with mitral valve prolapse (MVP).Material and methods. The retrospective non-randomized single-center study included 233 patients who underwent surgical treatment of severe mitral regurgitation due to MVP. Preoperative drug therapy was assessed using case records. Transthoracic echocardiography was performed in all patients before surgery. Pathological and immunohistochemical analysis of mitral valve fragments removed during surgery were performed. The serum content of TGF-β1 and TGF-β2 was determined by the enzyme immunoassay.Results. According to echocardiography, mitral valve leaflets were significantly longer and thicker in patients in the control group than in the ARB group. These data were confirmed by pathological study — most patients in the control group had excessive myxomatous mitral valve leaflets (χ2=7,9; p=0,005). In the ARB group, the expression of type III collagen in the mitral valve leaflets was lower compared to the control group and the expression of fibulin-5 did not differ. Also, in the main group, an increased density of valvular interstitial cells was found, including those expressing TGF-β1 and TGF-β2 compared to the control group. The serum level of TGF-β1 and TGF-β2 was significantly higher in the control group than in the ARB group.Despite the absence of differences in LV ejection fraction between the groups, global longitudinal systolic strain and strain rate were significantly higher in the main group.Conclusion. This is the first study to reveal a positive effect of ARB therapy on myxomatous mitral valve degeneration and LV function due to inhibition of the TGF-β signaling pathway, which opens up potential for pathogenetic therapy in patients with MVP.

Valvular heart disease remains one of the causes of cardiovascular morbidity and mortality worldwide. Aortic stenosis is the most common valvular pathology requiring cardiac surgery. For elderly and senile patients with high risks of volumetric cardiac surgery, a new type of biological prosthesis, a transcatheter implantable aortic valve, has become a solution to the problem. Over the past decade catheter interventions for severe valvular heart disease have evolved from balloon dilatation of native stenotic valves to replacement and reconstructive intervention of diseased valves. Transcatheter aortic valve implantation, which is widespread in the USA and Europe, has also begun to be performed in our country, primarily in comorbid groups of patients. Rapid technological advances in device design are likely to improve immediate and long-term outcomes of surgery and expand the current indications for transcatheter aortic valve implantation. The article analyzes the indications for the procedure in accordance with the latest recommendations of 2021, possible complications of the transcatheter aortic valve implantation, as well as the principles of patient management after the procedure, including the principles of drug therapy in this group of patients. Separately, the topic of aortic regurgitation and the possibility of transcatheter aortic valve implantation are touched upon, since this pathology is a new indication that has appeared only in the latest recommendations of the European Society of Cardiology. In this review, we want to acquaint physicians with the indications for transcatheter aortic valve implantation, the main complications, and the principles of managing patients in the perioperative period. The complication rate after transcatheter aortic valve implantation is decreasing due to technical advances and experience of interventional surgeons. In-depth knowledge of potential complications and their prevention plays a key role in improving the immediate and long-term results of surgery.

Cardiac fibrosis is the basis of structural and functional disorders in patients with diabetes mellitus (T2DM). A wide range of laboratory and instrumental methods is used for its prediction. The study aimed to identify simple predictors of cardiac fibrosis in patients with T2DM based on the analysis of circulating fibrosis biomarkers and arterial stiffness. The study included patients with T2DM (n = 37) and cardiovascular risk factors (RF, n = 27) who underwent ECHO, cardiac magnetic resonance imaging (MRI), pulse wave analysis (PWV), reactive hyperemia (RH), peripheral arterial tonometry, carotid ultrasonography, and assessment of serum fibrosis biomarkers. As a control group, 15 healthy subjects were examined. Left ventricular concentric hypertrophy was accompanied by an increased serum galectin-3 level in T2DM patients. There was a relationship between the PICP and HbA1c levels in both main groups (R2 = 0.309; p = 0.014). A negative correlation between PICP level and the global longitudinal strain (GLS) was found (r = −0.467; p = 0.004). The RH index had a negative correlation with the duration of diabetes (r = −0.356; p = 0.03), the carotid-femoral PWV (r = −0.371; p = 0.024), and the carotid intima-media thickness (r = −0.622; p < 0.001). The late gadolinium-enhanced (LGE) cardiac MRI was detected in 22 (59.5%) T2DM and in 4 (14.85%) RF patients. Diabetes, its baseline treatment with metformin, HbA1c and serum TIMP-1 levels, and left ventricle hypertrophy had moderate positive correlations with LGE findings (p < 0.05). Using the multivariate regression analysis, increased TIMP-1 level was identified as an independent factor associated with cardiac fibrosis.

Background: Left ventricular (LV) remodeling could be found in a range of connective tissue disorders with involvement of transforming growth factor (TGF)-beta pathway. Only rare data are available on it in patients with mitral valve prolapse (MVP). Objectives: The aim of the study is to assess mechanisms of myocardial remodeling and diastolic dysfunction in asymptomatic young patients without mitral regurgitation. Methods: 78 asymptomatic young subjects with MVP were consecutively enrolled in our observational, single-center study. Concentrations of TGF-beta 1 and -beta 2 in serum were determined by enzyme-linked immunosorbent assay. Standard echocardiography extended with speckle-tracking echocardiography was performed in all patients. Results: Levels of TGF-beta 1 (15.2 +/- 12.3 ng/ml vs. 9.3 +/- 7.7 ng/ml; p = 0.004) and -beta 2 (3.0 +/- 1.9 ng/ml vs. 2.5 +/- 1.2 ng/ml; p = 0.04) in serum were significantly higher in patients with MVP. LV myocardial mass index in patients with MVP did not differ from the controls but in MVP group there were more patients with concentric and eccentric hypertrophy. Significant deterioration of longitudinal early diastolic strain rate (SRe) was found in patients with MVP in the region of the interventricular septum (1.38 +/- 0.22 s(-1) vs. 1.54 +/- 0.25 s(-1); p = 0.00001) and anterior wall (1.44 +/- 0.23 s(-1) vs. 1.56 +/- 0.22 s(-1); p = 0.0007). In MVP group level of TGF-beta 2 correlated with LV mass index and SRe. Multivariate regression analysis between such factors as age and sex detected influence TGF-beta 2 concentration on SRe (OR 1.95; 95% CI 1.3-4.1; p = 0.01). Conclusion: A circulating TGF-beta is involved in the LV remodeling and deterioration of the diastolic function in MVP patients without significant mitral regurgitation, apparently due to the profibrotic nature of this cytokine.

Marfan syndrome is a hereditary, autosomal disease with a relatively high prevalence in the general population. Numerous manifestations of Marfan syndrome are expressed in a wide range of disorders involving cardiovascular, ocular and musculoskeletal systems. The article describes the principles of management of the syndrome in children and adolescents. Clinical manifestations of the disease are evaluated in young patients of different age groups. There are presented data on the main medicines used in the therapy of Marfan syndrome, such as beta-blockers, angiotensin receptor blockers, statins. Relevant literature was searched using the databases PubMed, MedLine, Scopus, Web of Science. The article will be interesting to a wide range of specialists: pediatricians, cardiologists, general practitioners and other specialties

According to contemporary views, hereditary connective tissue disorders divided classified Marfan syndrome, Loeys-Dietz’s, Ehlers-Danlos syndrome, the primary mitral valve prolapse. It is known that the fibrillinopaty, which include the Marfan syndrome and Loeys-Dietz’s is characterized by activation of TGF-β signaling pathway. With high le vels of TGF-β attributed most of these clinical manifestations these diseases – aneurysm of the aorta, arahnodaktylya, duralectasy. Assessment of the activity of TGF-β in persons with marfanoid habitus has not previously been studied. Materials and methods. As part of this work, surveyed 70 people: 61 patients young age (median age of 20.1 ± 2.1 years), among which 36 boys and 25 girls and 9 men with verified diagnosis Marfan syndrome (median age 27.9 ± 9.3 years). All survey performed Echocardiography with a targeted search of small anomalies of heart. Results. Correlation analysis showed a direct and reliable connection between arahnodaktylya and concentration of TGF-β1 in serum (r = 0.4, p = 0.05). For young people with signs of marfanoid habitus are characterized by reliably a higher concentration in the serum of both isoforms of TGF-β. Excess of threshold levels of TGF-β1 revealed at 20% of the core group and not found at all in the control (p < 0.05). Among persons with exceedances of threshold values for at least one faction of the TGF-β patients with signs of marfanoid habitus met almost three times more often than in the group with normal values of TGF-β (p = 0.01, χ2 = 5.58). In the group of persons with marfanoid habitus and increases TGF-β are detected more frequently such as atrial septal aneurysm, false chord left ventricle papillary muscles, incremental, deflection of shutters of the mitral valve in 1-2 mm, asymmetry tricuspid aortic valve.

Aneurysm of the thoracic aorta of any origin is traditionally considered a pathology for surgical correction. Traditionally the patients are referred for the surgery (prosthetics or endovascular treatment) when thoracic aorta diameter achieves 50–55 mm. However, the management strategy and conservative treatment in case of the smaller aorta dilations are not well elucidated in еру guidelines. The medication therapy aims at the decrease of the hemodynamic stress in the aortic wall, as well as at the correction of risk factors and accompanying diseases, including coronary heart disease, diabetes mellitus, hypertension, etc. Since drug therapy of this pathology is not sufficiently developed, its choice is difficult for physicians. The paper reviews the main groups of drugs and their effectiveness in patients with thoracic aorta aneurism resulted from different causes, including atherosclerosis, genetic pathology (Marfan syndrome, Loeys-Dietz syndrome, etc.). Currently, no drugs are considered as first line therapy. The evidence suggests the use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers only in genetic pathology.

OBJECTIVES: The term “Marfan cardiomyopathy” is used to indicate changes in left ventricular function in the absence of significant valvular pathology in Marfan syndrome. It is still unknown if there are any changes in cardiac function in patients with similar connective tissue abnormality such as marfanoid habitus. METHODS: In the study were included 98 persons - 8 patients with Marfan syndrome, 24 with marfanoid habitus and 66 healthy subjects. Echocardiography was performed to all patients. Speckle tracking echocardiography was used to assess the left ventricular deformation indices. Concentrations of transforming growth factor-β1 and -β2 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: Systolic left ventricular function was significantly lower in the Marfan syndrome group; as well global longitudinal left ventricular strain worsening was detected in MS group comparing to control group. In marfanoid habitus subjects, we found significant decrease of the circumferential strain in the interventricular septum and inferior wall. transforming growth factor-β1 and -β2 serum levels were elevated in patients with Marfan syndrome. Elevation of transforming growth factor-β1 was statistically nonsignificant unlike to transforming growth factor-β2 in the marfanoid habitus group. Negative correlations between the serum level of transforming growth factor-β2 and systolic radial strain in the marfanoid habitus group also have been found. CONCLUSION: Worsening of regional myocardial deformation may be the first sign of deterioration of the left ventricular systolic function and the existence of primary cardiomyopathy in asymptomatic marfanoid habitus patients, which could affect their long-term prognosis and may be caused by increased transforming growth factor-β signaling.

Marfan syndrome is a common genetically determined pathology of connective tissue. It was showed a reduction in systolic and diastolic left ventricular function in patients with Marfan syndrome, as well as the increase in left ventricle size, regardless of previous surgical intervention. Now in literature use the term “cardiomyopathy in Marfan syndrome,” denoting changes of the left ventricular function, in the absence of hemodynamic reasons for its deterioration. In this paper we evaluated the morphological and functional characteristics of the left ventricle, not only in patients with Marfan syndrome, but also in patients with marfanoid habitus.Materials and methods. The study included 98 people, 8 of them – patients with Marfan syndrome, 24 examinees with marfanoid habitus and 66 healthy examinees – control group. To all patients entered into the study, echocardiography was performed. Additionally global and local deformation of the myocardium using techniques speckle tracking was assessed.Resultssignificant difference circumferental deformation parameters of the anterior and lateral walls of the left ventricle and its statistically significant reduction in the group with marfanoid habitus was obtained.Conclusionsimpaired regional contractility may be the first sign of cardiomyopathy in patients with Marfan syndrome and in such a dysplastic phenotype as marfanoid habitus that is likely associated with hereditary disorders of the structure and function of connective tissue in various states of dysplastic phenotipes.

The article focuses on the review of the main methods of aorta visualization. The methods are described, as the algorithm of investigation method selection, strategy of patient’s management with aorta dilation. Special attention is paid for the patients with genetic disorders that may cause aorta dilation.

AbstractA 33-year-old woman underwent successful vaginal delivery despite previously unsuspected 8-cm ascending and 6-cm descending aortic aneurysms. These were repaired immediately after delivery.

Objective To evaluate outcomes of aortic valve-sparing operations in patients with aortic root aneurysms (ARA) combined with aortic insufficiency (AI) Methods Since March 2006, in our clinic 264 patients with ascending aortic aneurysms were operated on. 140 patients had ARA combined with aortic valve (AV) disease. 50 patients underwent aortic valve-sparing surgery. We performed 49 Tirone David I (TD-I) and 1 Yacoub procedures. Additional procedures were hemiarch repair (n = 1), mitral valve repair (n = 9) and CABG (n = 6). We assessed hospital and long-term results of aortic valve-sparing operations. Results Total hospital (30-day) mortality was 4% (n = 2). 2(4%) patients required reoperation due to post-operative bleeding. Echocardiography showed none or trivial AI in 38%, mild AI in 54% and moderate AI in 8%. We revealed positive correlation between residual AI and size of aortic annulus, previous AI grade, and size of aortic prosthesis (optimal result in linear aortic graft size 3–5 mm exceeding aortic annulus size). Follow-up was 60% completed. Late mortality was 2% (1 patient). Echocardiography revealed none or trivial AI in 53%, mild AI in 20%, moderate AI in 17% and severe AI in 10% (3 patients). One patient required reoperation 3 years after TD-I operation, the AV replacement with mechanical prosthesis was performed. Another two patients with severe AI are under close surveillance due to normal LV size and NYHA class 1–2. We revealed positive correlation between late AI and residual AI grade, and aortic leaflets coaptation point (optimal result in cases with location of coaptation point at the aortic annulus level or 1–2 mm upper). Conclusions TD-1 aortic valve-sparing reimplantation is optimal method of treatment in patients with ARA, AI and unaltered AV leaflets. Concordance of linear aortic graft size 3–5 mm exceeding aortic annulus and positioning of AV leaflets coaptation point at the level of aortic annulus or 1–2 mm upper are precursors of good result of valve-sparing operation.

Aim. To assess the causal factors in the development of thoracic aortic aneurysm. Despite the existing screening programmes, widely used visualisation methods, and improved intervention techniques, aortic aneurysm remains one of the leading causes of sudden cardiac death. The existing evidence on the causal factors in the development of thoracic aortic aneurysm is contradictory. Material and methods. We analysed medical histories of the patients hospitalized for thoracic aortic stenting from early 2011 to May 1 2012. The age and gender composition of the sample and the main causal factors resulting in the development of thoracic aortic aneurysm were assessed. Results. In total, 90 patients underwent thoracic aortic stenting. The main causes for the development of thoracic aortic aneurysm were: bicuspid aortic valve (n=30, 34%), atherosclerosis (n=30, 34%), and Marfan syndrome (n=10, 95). In 45 intraintervention biopsy samples, cystic medial necrosis was found in 55%, atherosclerosis in 27%, and normal tissue in 15% (n=12). Conclusion. The most common concomitant pathology in patients with thoracic aortic aneurysm was bicuspid aortic valve, aortic atherosclerosis, and hereditary connective tissue disorders. The main causal factor in the development of thoracic aortic aneurysm was cystic medial necrosis.

Ekaterina Luneva*, Eduard Malev, Anton Rizhkov and Artem Pakhomov a Department of Connective Tissue Disorders, Almazov’s Federal Centre of Heart, Blood and Endocrinology, St Petersburg, Russia b MRI Department, Almazov’s Federal Centre of Heart, Blood and Endocrinology, St Petersburg, Russia * Corresponding author. 2 Akkuratovastr, St Petersburg, Russia. Tel: +7-8127023749; fax: +7-8127023744; e-mail: e.luneva@hotmail.com (E. Luneva). Received 18 February 2013; received in revised form 18 April 2013; accepted 22 April 2013

The paper reviews general factors underlying the variety of clinical manifestations of inherited connective tissue disorders (ICTD). The authors make an attempt to harmonise the existing ICTD terminology with the standard international classification. It is proposed to use the Russian term “dysplasia” as a synonym of ICTD and to divide all ICTD into inherited syndromes (IS) and dysplastic phenotypes. An example of fibrillinopathies is used to consider the clinical polymorphism and genetic heterogeneity of IS. The clinical significance of Marfanoid habitus as a phenotype is also discussed.

Aim. To assess the causal factors in the development of thoracic aortic aneurysm. Despite the existing screening programmes, widely used visualisation methods, and improved intervention techniques, aortic aneurysm remains one of the leading causes of sudden cardiac death. The existing evidence on the causal factors in the development of thoracic aortic aneurysm is contradictory. Material and methods. We analysed medical histories of the patients hospitalized for thoracic aortic stenting from early 2011 to May 1 2012. The age and gender composition of the sample and the main causal factors resulting in the development of thoracic aortic aneurysm were assessed. Results. In total, 90 patients underwent thoracic aortic stenting. The main causes for the development of thoracic aortic aneurysm were: bicuspid aortic valve (n=30, 34%), atherosclerosis (n=30, 34%), and Marfan syndrome (n=10, 95). In 45 intraintervention biopsy samples, cystic medial necrosis was found in 55%, atherosclerosis in 27%, and normal tissue in 15% (n=12). Conclusion. The most common concomitant pathology in patients with thoracic aortic aneurysm was bicuspid aortic valve, aortic atherosclerosis, and hereditary connective tissue disorders. The main causal factor in the development of thoracic aortic aneurysm was cystic medial necrosis.

The article is dedicated to main principles of Marfan syndrome diagnostics in the light of new Ghent nosology2010. Special attention is paid to differential diagnostics of this disease.