Effects of Mitral Valve Surgery on Ventricular Arrhythmia in Mitral Valve Prolapse Patients: Five-Year Eollow-up.

Aim      To evaluate the effect of mitral valve (MV) repair and replacement on the incidence of ventricular arrhythmias (VA) and to identify risk factors for the persistence of VA in patients with MV prolapse and severe mitral regurgitation (MR) during a mid-term follow-up.Material and methods  A single-site observational, prospective study successively enrolled 30 patients (mean age, 55.2±9.9 years, 60% men) who underwent MV repair or replacement for severe MR due to MV prolapse or chordal avulsion. Transthoracic echocardiography and Holter monitoring were performed in all patients before and annually after surgery. A pathomorphological study of MV fragments excised during surgery was performed.Results During the five-year follow-up period (144 person-years), one case of sudden cardiac death outside a health care facility was recorded. MR severity progressed in three patients after MV repair. The total number of all VAs decreased during the follow-up period, with a significant decrease in the number of paroxysms of unstable ventricular tachycardia during the first two years after surgery. The presence of VA in the postoperative period was correlated with the severity of postoperative left ventricular (LV) remodeling: end-diastolic volume (EDV) (rs=0.69; p=0.005), LV ejection fraction (EF) (rs = -0.55; p=0.004) and severity of MV myxomatous alterations according to histological study data (rτ=0.58; p=0.045). The beta-blocker treatment did not influence the VA frequency and severity (rs= -0.18; p=0.69). According to a univariate regression analysis only EDV (p = 0.001), LVEF <50% (p = 0.003), and myxomatous MV degeneration (p = 0.02) were risk factors for persistent ventricular tachycardia in the postoperative period.Conclusion      Surgical intervention on MV in patients with MV prolapse and severe MR decreased the number of cases of malignant VAs and was correlated with the postoperative changes in LV volume and function, as well as the severity of MV myxomatous alterations.

[Electroencephalogram features in children with congenital hyperinsulinism treated according to the international protocol in Russian Federation].

BACKGROUND: Congenital hyperinsulinism (CHI) is a rare life-threatening disease characterised by persistent hypoglycaemia as a result of inappropriate insulin secretion, which can lead to irreversible neurological defects in infants. AIM: To evaluate neurophysiological characteristics of central nervous system in children with congenital hyperinsulinism treated according to the international protocol in Russian Federation. MATERIALS AND METHODS: Our retrospective, prospective cohort study included 73 patients who received treatment for CHI according to the current international protocol at different departments of the Almazov National Medical Research Centre from 2017 to 2022. All patients underwent a comprehensive examination, including electroencephalography (EEG). RESULTS: Among 73 patients with CHI, 35% (23) had focal form of the disease, 65% had non-focal form (49% (39) - diffuse form, 16% (11) - atypical form). All patients with focal form of CHI had a recovery as an outcome.Analysing the EEG data we found that paroxysmal activity was recorded in 23 patients (32%), 50 patients did not have paroxysmal activity (68%). Diffuse changes were observed in 47 patients (64%), whereas 26 patients (36%) were absent of it. By constructing Kaplan-Meier curves we found that the alpha rhythm is formed significantly (p=0.026) earlier in patients with a focal form of CHI. CONCLUSION: CHI patients treated according to the international guidelines in Russian Federation show rather positive neurological outcome. We established that alpha rhythm earliest formation is associated with focal form of CHI.

[Causes and mechanisms of sudden cardiac death in children]. / Prichiny i mekhanizmy vnezapnoi serdechnoi smerti u detei.

The paper presents basic morphological criteria of the diagnosis of sudden cardiac death related to different diseases in young people. Attention is drawn to cardiomyopathies, channelopathies, connective tissue dysplasias, Marfan syndrome with cystic medial necrosis, sudden arrhythmic death. Initiating events in sudden cardiac death are discussed. Besides morphological manifestations, the paper dwells upon major genetic events and clinical presentation of the diseases. It is based on both existing publications and own data.

Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions.

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.

[Combination of tumors of different histogenesis in pediatric neurosurgery]. / Sochetanie opukholei razlichnogo gistogeneza v detskoi neirokhirurgii.

Multiple gliomas are determined by synchronous two or more tumors located in different brain regions. It is important to distinguish multiple primary tumors and metastatic brain lesion. In the first case, tumor spread can`t be explained by dissemination along the cerebrospinal fluid pathways, commissural fibers or local metastases. Multiple primary tumors with different histological structures are called bidermal neoplasms. Surgery is preferred in these patients with severe symptoms. The purpose of surgery is maximum resection of tumor. Follow-up may be advisable for small tumors without clinical manifestations. Treatment of multiple gliomas includes surgery, radiotherapy and chemotherapy. Multiple tumor process in children is much more severe compared to a single neoplasia that requires neurological and neuroimaging control and determines treatment strategy. The authors report 3 children with multicentric gliomas, discuss the various aspects of diagnosis and treatment of multiple gliomas and formulate the recommendations for the treatment based on own clinical experience and literature data.

Perivascular Innervation of the Pulmonary Artery in Human and Swine: A Comparative Study for the Development of an Experimental Model of Denervation.

For studying the possibility of using catheter denervation of the pulmonary artery for the treatment of pulmonary hypertension, large animals, such as pigs, are more suitable, because the diameter of the pulmonary artery in this case allows manipulation of the ablation catheter. The study of the perivascular adipose tissue of the trunk and bifurcation of the pulmonary artery in humans and pigs revealed differences in the density and diameter of nerve fibers, but their depth did not differ. Immunohistochemical analysis with different markers of the autonomic nervous system receptors revealed similar receptor profile in human and pigs, though the expression of all studied markers in pigs was less pronounced than in humans. These findings attest to similarity of the innervation of the pulmonary arteries in humans and pigs under normal conditions.

[Clinical significance of different assesment methods of myocardial fibrosis in patients with hypertrophic cardiomyopathy.]

Objective To evaluate prospects for clinical use of circulating biomarkers for characterizing fibrotic changes in the myocardium of patients with hypertrophic cardiomyopathy (HCMP) with left ventricular (LV) outflow tract obstruction.Materials and Methods This was a prospective study with a 12-month follow-up period. The study included 47 patients (29 females and 18 males) with obstructive HCMP who were selected for septal reduction. Echocardiography (EchoCG), cardiac magnetic resonance imaging (MRI) and measurements of serum C-reactive protein, N-terminal pro-brain natriuretic peptide, and relevant circulating markers of fibrosis (TGF-ß1, MMP-2,-9, TIMP-1, galectin-3, sST2, CITP, PICP, and PIIINP) were performed for all patients. All patients were evaluated at baseline and at 7 days, 6 and 12 months following surgical treatment. Morphometrical analysis of intraoperative biopsy samples was performed for evaluation of the degree of fibrotic changes. Patients received beta-blockers (95.7%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (34%), loop diuretics (68.1%), aldosterone antagonists (34%), and statins (66%).Results Women with HCMP were older and more frequently had additional risk factors (arterial hypertension). Men had a higher risk of sudden cardiac death. Histological study of intraoperative myocardial biopsy samples showed that the area of fibrotic changes was 13.9±6.9%. According to cardiac MRI mean area of delayed contrast enhancement was 8.7±3.3% of LV myocardial mass. No association was established between traditional cardiovascular risk factors and severity of myocardial fibrotic changes or levels of circulating fibrosis markers. Perhaps that was due to the modifying effect of the drug therapy received by HCMP patients. According to EchoCG maximum pressure gradient in the LV outflow tract before the surgical treatment was 88 (55; 192) mm Hg, and interventricular septal thickness was 22 (16; 32) mm. A considerable decrease (p=0.0002) in the LV outflow tract gradient was observed after myectomy in all patients. At the same time, the left ventricular dimension, which tended to decrease in the early postoperative period, returned to baseline values by the 6th month of follow-up.Conclusion The study confirmed the increase in relevant circulating markers of fibrosis in patients with obstructive HCMP. At the same time, no correlation was observed between levels of circulating biomarkers and severity of fibrosis according to data of histology and cardiac MRI, which was probably due to the modifying effect of drug therapy and limited sampling.

[The Case of Fulminant Myocarditis].

Fulminant myocarditis (FM) is a severe form of inflammatory myocardial injury rapidly developing as acute heart failure, cardiogenic shock, or life-threatening disturbances of cardiac rhythm. FM requires intensive treatment including drug therapy, mechanical circulatory support, and in some cases - heart transplantation. Echocardiography can be used as a screening method of diagnostics. Magnetic resonance imaging of the heart often cannot be performed because of hemodynamic instability of a patient, therefore endomyocardial biopsy with histological and immunohistochemical studies as well as molecular-genetic analysis of obtained samples is required for final diagnosis. Prognosis of the disease is determined by histological picture. In most cases, after cessation of acute stage of the inflammatory process, FM has a favorable long-term prognosis. In this article we present a clinical case of FM and review of current literature on diagnosis and treatment of this disease.

[Clinical, genetic, and radionuclide characteristics of the focal form of congenital hyperinsulinism].

BACKGROUND: Congenital hyperinsulinism (CHI) is a severe disease with a high risk of complications including neurological deficit. Persistent hypoglycemia in patients with focal form of CHI can not be managed with medical treatment in 96.4% of cases, what subsequently leads to surgical treatment. Currently, there is a lack of information regarding patients with focal form of CHI. This study is aimed at finding better approaches for diagnosis and treatment of patients with focal form of CHI. AIMS: To study clinical, genetic and PET/CT findings of the focal form of CHI in Russian group of patients. MATERIALS AND METHODS: The observational research included all patients with a histologically confirmed focal form of CHI, who were admitted to Endocrinology Research Centre during the period from January 2008 to January 2019. A statistical analysis of clinical data, genotype, and positron emission tomography (PET) with 18F-dihydroxyphenylalanine (18F-DOPA) was performed. The median follow-up was 18 months. RESULTS: The study included 31 patients with focal CHI (14 boys, 45.2%). All patients had a neonatal presentation of the disease and demanded high levels of continuous glucose infusion to maintain euglycemia. The difference between the age of hypoglycemia presentation and the age of diagnosis ranged from 1 day to 3.9 months. In all cases, diazoxide was found to be ineffective. However, in 9 patients, it was possible to withdraw continuous glucose infusion and maintain euglycemia using octreotide in the preoperative period. A molecular genetic study allowed us to detect diverse pathogenic variants in ABCC8 and KCNJ11 genes in 30 patients. According to PET data with 18F-DOPA, the pancreatic index (PI) varied widely from 1.16 to 3.59. After partial resection of the pancreatic region with insulin hypersecretion, all patients showed complete recovery. CONCLUSIONS: The focal form of CHI is a severe condition with high prevalence of neurological complications. For preoperative diagnosis of the morphological form of the disease, it is necessary to conduct genetic analysis and radionuclide studies. Solely evaluation of mathematical parameters in 18F-DOPA PET without taking into account the visual data and the results of genetic analysis does not allow establishing the robust diagnosis. Timely diagnosis, identification of risk factors, and prevention of complications of persistent hypoglycemia are important tasks for clinicians.

[Interventional treatment in patients with myocarditis: Pro and Contra].

AIM: Ventricular tachyarrhythmias (VTs) are often encountered in patients with inflammatory heart diseases. VT can become lifethreatening in patients with myocarditis, and the management may vary in different types of myocarditis. Purpose of the study is to describe VT characteristics in patients with verified myocarditis, and to evaluate the efficacy and safety of VT management, when tailored to the type of myocarditis. MATERIALS AND METHODS: Study population comprised: 56 patients with morphologically verified myocarditis; 18 patients with primary cardiomyopathy (control group). All patients underwent full clinical evaluation, endomyocardial biopsy (including immunohistochemical analysis). Forty (54 %) patients underwent radiofrequency catheter ablation of VT. An implantable cardioverter-defibrillator (ICD) was inserted in 17 patients. RESULTS: There was no statistically significant difference between myocarditis and primary cardiomyopathy groups by demographic and echocardiographic data. In myocarditis group, nonsustained VT and/or frequent premature ventricular beats were seen in 59 % of patients; sustained VT in 12,5 % subjects, 1 patient had a history of ventricular fibrillation. VT ablation was associated with a significant decrease in VT recurrence (p=0,0009) during the follow-up period. Active myocarditis was associated with a higher VT recurrence rate (67 % in active vs. 19 % in borderline myocarditis). Among patients with ICD implantation, only one subject (with active myocarditis at admission) had life-threatening ventricular arrhythmia. CONCLUSION: In this selected group of patients with verified myocarditis and clinically significant VTs, catheter ablation seems at least partly effective. Patients with borderline myocarditis and symptomatic VTs may benefit from ablation. Therefore, morphological diagnostic of myocarditis can be a key point in choice of treatment.

[Left ventricular noncompaction: A clinical and morphological study].

The data of clinical, macro- and micrometric, histological, and immunohistochemical studies of the heart were analyzed in patients with left ventricular noncompaction (LVNC). Materials from 7 patients: 5 hearts of recipients after heart transplantation, one heart of a dead patient, and one endomyocardial biopsy specimen were investigated. The investigations showed that this disease was accompanied by a preponderance of a noncompact layer with its ratio to a compact layer (2.4:6.6) in the left ventricle and by myocardial hypertrophy and fibrosis in all cases, by endocardial fibroelastosis and discomplexation of muscle fibers by more than 15% of the specimen area in 6 of the 7 cases, by right ventricular hypertrabeculation and myocarditis in 5 cases, and by lipomatosis and impaired connexin 43 expression in 4 cases. Only one of the four patients was found to have MYH 7 gene mutation. The results of MRI of the extracted heart coincided with morphological findings in 100% of cases. The comparative study demonstrated that this disease had simultaneously morphological features of both LVNC and restrictive, hypertrophic, dilated cardiomyopathy. The findings may suggest that the LVNC phenotype may be formed under the influence of various modifying factors (hemodynamic and inflammatory ones).

[Autoimmunity and Prognosis of Patients With Morphologically Documented Myocarditis].

AIM: to assess clinical and prognostic value of circulating cardiospecific autoantibodies (AAB) and CD4+ T-regulatory cells in patients with myocarditis. MATERIAL AND METHODS: We included into this study 47 patients with lymphocytic myocarditis verified by analysis of histological and immunohistochemical data. Comparison group consisted of 30 practically healthy persons. Content of marker cardiotropic AAT were measured with the help of standardized immune enzyme test-systems. Number of circulating CD4+CD25+ and CD4+CD25+FoxP3+ T-lymphocytes were evaluated by flow cytometry. RESULTS: Among factors determining prognosis of patients with lymphocytic myocarditis factors of key significance were the presence of clinically overt heart failure at the disease debut, and degree of reduction of left ventricular ejection fraction. Distinctive feature of active myocarditis was elevation of titer of AABs to sarcomeric, cytoskeleton, and cytoplasmic proteins of cardiomyocytes, as well as elevated level of AABs to various epitopes of adenine nucleotide translocator. Elevated level of AAB to 1-adrenoreceptors was an independent predictor of unfavorable outcome in patients with lymphocytic myocarditis. Increased population of circulating CD4+CD25+ T-regulatory cells was as sociated with elevated concentration of of natriuretic peptide. CONCLUSION: Abnormalities in the system of autoimmunity play key role not only in pathogenesis but also in prognosis of inflammatory myocardial diseases. Changes of profile of circulating cardiospecific AABs and T-regulatory cells can bear a protective function.

[Primary and secondary hypophysitis: A clinicomorphological study]. / Pervichnyi i vtorichnyi gipofizit. Kliniko-morfologicheskoe issledovanie.

The paper describes 6 cases of the rare disease - primary and secondary hypophysitis detected by a morphological examination of the material of endoscopic transsphenoidal resection of pituitary neoplasms. It also provides clinical and morphological comparisons and analyzes the data available in the literature.

[Rosuvastatin in Coronary Bypass Surgery: Whether Only Secondary Prevention?]

BACKGROUND AND AIM: The increasing number of coronary artery bypass grafting (CABG) is associated with a need for active introduction of methods improving immediate and long-term results of these interventions. Results of a number of studies conducted during recent years allow to consider high dose statin therapy one of such methods. In this article we present results of rosuvastatin administration to patients with ischemic heart disease (IHD) prior to surgery. METHODS: Rosuvastatin (40 mg/day) was given for 4 weeks before CABG to patients who had previously taken simvastatin (20 mg/day). RESULTS: This regimen was assocaed with reduction of desquamation of endothelium of the intima, reduction of the number of smooth muscle cells in the media, as well as the proliferation index according to the immunohistochemical analysis in sections of the great saphenous vein selected for the coronary anastomosis. CONCLUSION: It is assumed that the antiproliferative effects of high-dose rosuvastatin therapy may have a positive impact in relation to the viability of a remote arterio-venous grafts.

[Histiocytoid cardiomyopathy concurrent with noncompact myocardium, myocarditis, and pericarditis].

The paper presents a practical case of histiocytoid cardiomyopathy concurrent with noncompact myocardium, atrial septal defects, myocarditis, and pericarditis in an 8-month-old girl, by describing their clinical presentations and a morphological examination.

[Morphological features of the myometrium in connective tissue dysplasia in women with uterine inertia].

OBJECTIVE: to reveal the morphological features of the lower uterine segment myometrium in connective tissue dysplasia (CTD) in women with uterine inertia. MATERIAL AND METHODS: Histological, immunohistochemical (with antibodies against collagen types I and III, matrix metalloproteinases 1 and 9 (MMR-1, MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), fibronectin; fibulin-5, connexin-43), electron microscopic, and electron immunocytochemical studies with morphometry of myometrial fragments from 15 parturient women with CTD and uterine inertia (a study group) and those from 10 women without CTD (a control group). RESULTS: The myometrium in CTD exhibited the decreased expression of connextin-43, fibulin-5, TIMP-1, collagens types I and III with collagen type III predominance and the unchanged levels of fibronectin and MMP-1 and MMP-9. Electron microscopy and immunocytochemistry showed fewer intercellular contacts and the dramatically lower expression of connexin-43 than in the control. CONCLUSION: A set of found myometrial changes in women with uterine inertia is a manifestation of CTD.

[A clinical case of diagnosis of left ventricular noncompaction myocardium in a patient with infectious myocarditis].

The paper describes a rare clinical case involving primary cardiomyopathy (noncompaction of the left ventricular myocardium (NCLVM), infectious myocarditis, and, possibly, hypertrophic cardiomyopathy (HCM). Objective, laboratory instrumental, invasive examination (coronarography with right ventricular endomyocardial biopsy) of the patient and histological study of his heart biopsy revealed acute infectious myocarditis concurrent with NCLVM and, possibly, HCM. The detection of a rare abnormality as NCLVM necessitates a meticulous additional examination to identify other primary cardiomyopathies (including HCM).

[Sclerodegenerative aortic valve lesions and hereditary connective tissue disorders].

AIM: To estimate the role of different dysplastic syndromes and phenotypes in the development of sclerodegenerative lesions and calcific stenosis of the aortic valve (AV). SUBJECTS AND METHODS: One hundred and fifty patients (82 men and 68 women) aged 42 to 83 years were examined. A study group consisted of 89 patients (mean age 60.7 +/- 8.9 years) with clinical and echocardiographic signs of sclerodegenerative AV lesions (SDAVL). A control group included 61 patients (mean age 61.3 +/- 7.6 years) who had no clinical, physical, or echocardiographic signs of SDAVL. Twenty-five patients with critical calcific aortic stenosis (CAS) underwent histological examination of removed aortic semilunar valves after prosthetic AV replacement. RESULTS: Persons with a Marfanoid habitus (18%) and mitral valve prolapse (10.7%) are most common in older age groups. An association has been found between the bone signs of dysmorphogenesis and the development of SDAVL and CAS. CONCLUSION: Three or more signs of bone dysmorphogenesis and the Marfanoid habitus should be viewed as a predictor of SDAVL.

[First experience of application of assist circulation device using biventricular type "excor"].

The frequency of use of assist blood device as the "bridge" to the heart transplantation increased in last years. An assessment of results of first 7 implantations of assist circulation device using biventricular type "Excor" was made. The implantations were performed in Federal Almazov centre of the heart, blood and endocrinology. An observation period after implantation was since 11 till 301 days. The heart transplantation of 4 patients was carried out in different terms after implantation. One of the patients passed away on the fifth day due to the pulmonary embolism. Another patient died on the eleventh day after the implantation because of multiple organ failure against the background of severe chronic cardiac failure. The waiting list of heart transplantation includes 2 patients.

[Intravital and postmortem morphological studies and magnetic resonance imaging of arrhythmogenic right ventricular dysplasia].

The authors conducted histological, immunohistochemical, and morphometric studies of 47 endomyocardial biopsies and 33 hearts with a high morphological criterion for the diagnosis of arrhythmogenic right ventricular dysplasia after F.I. Marcus et al. (2010), as well as intravital and postmortem cardiac magnetic resonance imaging (MRI). The average residual cardiomyocyte area was 39.7 +/- 12.8%, and the average cardiomyocyte diameter was 10.4 +/- 1.5 microm. Muscle fiber atrophy, lipomatosis, and fibrosis in the right ventricle were detected in all cases, myocarditis in 44%, mitral valve prolapse in 42%, and muscle fiber dyscomplexation in the right ventricular in 33%. The most informative signs for the diagnosis of arrhythmogenic right ventricular dysplasia using MRI are right ventricular contraction dyssynchrony and those using a morphological study are a residual cardiomyocyte area and muscle fiber atrophy in the right ventricle. A decrease in or focal absence of gamma-catenin expression in the muscle fibers was observed only in 60% of the patients.