Background: the whole spectrum of Immune Checkpoint Inhibitors (ICI) associated cardiovascular immune related adverse events is not fully understood. Only last years it became clear that ICI may cause not only inflammatory cardiovascular diseases. And recent prospective studies have shown subclinical left ventricular disfunction progression in patients treated with ICI but results are bit discordant. Also, specific risk factors of ICI related cardiovascular adverse events didn’t clear yet. Methods: single canter prospective observational study enrolled sixty patients with cancer and indications for ICI. All patients underwent cardiovascular examination before antitumor therapy (n=60), as well as at 3 months (n=34) and 9 months (n=15) following its initiation. The standard examination protocol included evaluation of laboratory parameters, echocardiographic assessment (incl. left ventricular deformation characteristics), Holter monitoring, carotid ultrasound. Results: no statistically significant changes were observed in serum creatinine, C-reactive protein, troponin I, NT-proBNP, and thyroid-stimulating hormone. At the 3-month follow-up, left ventricular (LV) end-systolic volume (ESV) increased from 38±12 ml to 41±11 ml (p=0.026), while LV ejection fraction (EF) decreased from 64% [61;66] to 62% [58;66] (p=0.043). After 9 months patients displayed a continued increase in LV ESV from 35±10 ml to 40±9 ml (p=0.044) and a decrease in LV EF from 64±4% to 60±6% (p=0.012). Additionally, there were observed increases in the diameter of the aortic sinuses of Valsalva (p=0.012), ascending aorta (p=0.046), left atrium (p=0.013), and right ventricle (p=0.011). There was a notable increase in the proportion of patients with atherosclerotic lesions in the carotid arteries, rising from 44% to 60% over the 3-month period (p=0.046). Throughout the follow-up period, novel cardiovascular events occurred in 23.3% of patients (n=14) and included asymptomatic decrease in LV EF and GLS, meeting the established criteria for cardiotoxicity. According to univariate Cox regression analysis, several independent predictors of new CVEs were identified included creatinine, left ventricular Tei index, initial NT-proBNP exceeding 500 pg/ml, TSH concentration, and treatment with anti-PD-L1 immune checkpoint inhibitor. Conclusion: we reveled the high incidence of novel cardiovascular events, presence of subclinical changes of echocardiography parameters, atherosclerosis progression. Also, we defined predictors of ICI related cardiovascular adverse events.

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.

Aim. To estimate the prevalence of disordered repolarization and its relation with the character of vegetative dysfunction in younger persons with MP and MVP.Material and methods. Totally 285 persons studied of the young age (mean age 19,4+1,4 y.). Phenotypical, anthropometric and clinical investigation performed, ECG, EchoCG, Holter monitoring (HM) of ECG and BP, treadmill test. The heart rate variability (HRV) was assessed, cardiovascular tests performed.Results. MP and MVP are the most common dysplastic phenotypes in younger persons and have 15% ad 10% prevalence, respectively. The analysis of the treadmill test results, done for 140 of participants (80 males) showed that the youths studied had good tolerance of physical exertion (PET at the average or high level). In men with MVP and MP comparing to almost healthy individuals there was tendency to the decrease of PET and slowed down recovery of BP and pulse rate, that witnesses the decrease of adaptation abilities in the assessed persons of those groups. Disordered repolarization on resting ECG and during exercise test was found in MVP and MP, as in controls. However, the prevalence of T inversion during exercise test in MVP and MP was much higher, than in controls. HRV and vegetative tests analysis did not reveal significant differences in vegetative regulation in persons with EVRS on resting ECG and in the group of DR with PE.

To study etiology of non-coronary ventricular tachyarrhythmia (VTA) based on the assessment of the endomyocardial biopsy data, 87 patients aged 39.9±1.7 years (50 men; 57.5%) were examined. The study group included 41 patients (47%) with episodes of sustained ventricular tachycardia (VT) and 46 patients (53%) with ventricular premature contractions (VPC) and/or non-sustained VT. Electrocardiography, 24 hour ECG Holter monitoring, echocardiography, magnetic resonance tomography with contrasting and in the fat suppression mode, stress test, and coronary angiography to exclude the VTA ischemic origin were performed. The endomyocardial biopsy was carried out in the area of surgical treatment of the arrhythmia, which included catheter ablation and/or implantation of a cardioverter-defibrillator. According to the data of endomyocardial biopsy, arrhythmogenic cardiomyopathy/right ventricular dysplasia (ACRVD) was diagnosed in 29 patients (33%), myocarditis, in 34 patients (39%), and postmyocarditic cardiosclerosis, in 24 ones (28%). The histological study of myocardial biopsy samples of the patients with ACRVD showed lipomatosis, microfocal fibrosis, as well as dystrophy and atrophy of the right ventricle muscular fibers. Signs of active myocarditis were found in 7 patients, of chronic myocarditis, in 2 ones. The relative area of lipomatosis was 34.3±14% (3 90%); 32.7±13.4% in patients without myocarditis and 42.1±22.3% in patients with myocarditis. The relative area of fibrosis was 36.7±18% (2 90%); 30±15% in patients without myocarditis and 37.2±17.2% in patients with myocarditis. Thus, the endomyocarial biopsy permits one to determine etiology of VTAs considered “idiopathic” during the standard (typical) non-invasive study. The most frequent causes of non-coronary ventricular arrhythmias were ACRVD (33%), myocarditis (33%), and post-myocarditic fibrosis (28%).

Aim. To determine the clinical features of arrhythmogenic right ventricular dysplasia (ARVD) in recipients on heart transplant waiting list (WL) and after a heart transplantation (HTx). Material and methods . From January 2010 to December 2018, we included 192 recipients in heart transplant waiting list (HTx WL) on behalf of Almazov National Medical Research Center. ARVD was diagnosed in 4 subjects (F Marcus et al. criteria, 2010). All 4 patients (female, mean age 46,5 years-old (16-54-year-old)) underwent HTx. Prior to HTx, arrhythmias (atrial fibrillation, atrial flutter) were diagnosed in 3 recipients. In patient №2, pacemaker in VVI mode was implanted due to sick sinus syndrome (SSS) and tachycardia-bradycardia syndrome and others underwent ICD implantation. Results. Survival after HTx was 30,9 (3,9-46,2) months. All recipients were treated with triple-drug immunosuppressive therapy (calcineurin inhibitors, mycophenolic acid, steroids) and induction with Basiliximab. All patients experienced high sensitivity to immunosuppressive therapy (agranulocytosis), and therefore a colony-stimulating factor was administered to all of them. After immunosuppression reduction (Tacrolimus plus Methylprednisolone) agranulocytosis did not recur. Conclusion. ARVD is a rare disease in the structure of end-stage heart failure in recipients in HTx WL. An examination of this pathology is necessary to manage patients on-time with surgical treatment (ICD, HTx). According to our results, causal variants in desmosome genes were determined in 1 from 4 patients and simultaneous presence of two unique genetic variants in the RKR2 gene were found in one. A special feature of post-HTx management was the development of agranulocytosis, which once again underlines the need for a personalized approach to the selection of the immunosuppressive therapy.

Objective. To study the etiology of nonischemic ventricular arrhythmias and to improve diagnostic evaluation of inlammatory myocardial disease using endomyocardial biopsy.Design and methods. We performed 100 endomyocardial biopsies during catheter ablation in patients with nonischemic ventricular arrythmias. Results. Myocarditis was veriied in 58 cases, and postinlammatory ibrosis — in 24 cases. Twenty three patients (67 %) demonstrated active myocarditis, 1 (2,9 %) had chronic active myocarditis, and 10 subjects (29 %) — chronic non-active myocarditis. Conclusion. Endomyocardial biopsy contributes to better veriication of the etiology of ventricular arrhythmias. Late gadolinium enhancement during magnetic resonance imaging shows 74 % sensitivity and 46,9 % speciicity in the evaluation of myocarditis, and 52,4 % sensitivity and 38,9 % speciicity in veriication of postinlammatory ibrosis. Presence of CD-8+ cells, Ig M, patchy dystrophin expression can be additional features for veriication of active myocarditis.

Aim. To assess autonomous regulation status in young patients with mitral valve prolapse (MVP), Marfanoid habitus (MH), and signs of systemic connective tissue involvement (SCTP). Material and methods. The study included 59 young men with MVP, MH, and SCTP. All participants underwent phenotypical and clinical examination, anthropometry, electrocardiography (ECG), echocardiography (EchoCG), Holter monitoring (HM) of ECG and blood pressure (BP), treadmill test, heart rate variability (HRV) assessment, and additional cardiovascular tests. Results. In patients with MVP, MH, and particularly SCTI, a significant decrease in daytime parameters of sinus arrhythmia was observed. These individuals were also characterized by significantly reduced spectral HRV parameters. A pathologic reaction to active orthostatic test was registered in 50% of the participants with MVP and MH. The overall assessment of autonomous regulation tests demonstrated the presence of abnormal reactions in more than 50% of MH individuals and in 80% of MVP patients. Conclusion. Autonomous dysfunction is common among young patients with MVP, MH, and SCTI.

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 autonomous regulation status in young patients with mitral valve prolapse (MVP), Marfanoid habitus (MH), and signs of systemic connective tissue involvement (SCTP). Material and methods. The study included 59 young men with MVP, MH, and SCTP. All participants underwent phenotypical and clinical examination, anthropometry, electrocardiography (ECG), echocardiography (EchoCG), Holter monitoring (HM) of ECG and blood pressure (BP), treadmill test, heart rate variability (HRV) assessment, and additional cardiovascular tests. Results. In patients with MVP, MH, and particularly SCTI, a significant decrease in daytime parameters of sinus arrhythmia was observed. These individuals were also characterized by significantly reduced spectral HRV parameters. A pathologic reaction to active orthostatic test was registered in 50% of the participants with MVP and MH. The overall assessment of autonomous regulation tests demonstrated the presence of abnormalreactions in more than 50% of MH individuals and in 80% of MVP patients. Conclusion. Autonomous dysfunction is common among young patients with MVP, MH, and SCTI.