[Applying of magnetic resonance tomography for assessment of cardiac remodeling and risk stratification in patients with pulmonary arterial hypertension].

Magnetic resonance imaging - is high precision method for diagnosing cardiovascular diseases. Simultaneously with the anatomy and function of the right ventricle, magnetic resonance imaging allows to assess the pulmonary circulation, which leads to the widespread use of this method in the diagnosis and dynamic monitoring of patients with pulmonary arterial hypertension. The article is devoted to the assessment of cardiac remodeling and risk stratification of this group of patients. Special attention is given to new prognostic parameters included in the scale for risk stratification of patients with pulmonary hypertension of the European Society of Cardiology/European Respiratory Society 2022.

["Guiding lights" for the diagnosis of chronic thromboembolic pulmonary hypertension in the flow of patients with pulmonary embolism].

On December 13, 2021, an expert council was held to determine the position of experts of different specialties regarding the reasons for the low level of diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in real clinical practice in a pandemic of a new coronavirus infection and possible ways to improve detection in patients with pulmonary embolism (PE) ) in history. The reasons for the low level of diagnosis of CTEPH are the insufficient level of knowledge of specialists, especially primary care physicians; lack of clear regulatory documents and expert centers for the management of this category of patients. Primary diagnosis of CTEPH in a pandemic can be strengthened through the widespread use of telemedicine for consultations of primary care physicians with specialists from expert centers; to maximize the role of echocardiography and computed tomography (CT) as differential diagnostic tools for dyspnea, in particular in patients with COVID-19. To increase the detection rate of CTEPH, diagnostic vigilance is required in patients with risk factors and episodes of venous thromboembolism. To improve the screening of CTEPH, it is necessary to create an algorithm for monitoring patients who have had PE; provide educational activities, including through the media; create materials for patients with accessible information. The regulatory documents should designate the circle of responsible specialists who will be engaged in long-term monitoring of patients with PE. Educational programs are needed for primary care physicians, cardiologists, and other physicians who come into the field of view of patients with CTEPH; introduction of a program to create expert centers for monitoring and managing patients with the possibility of performing ventilation-perfusion lung scintigraphy, cardiopulmonary stress test, CT, right heart catheterization. It seems important to build cooperation with the Ministry of Health of Russia in order to create special protocols, procedures for managing patients with PE and CTEPH.

[A rare clinical case of the patient with pulmonary hypertension associated with hereditary hemorrhagic telangiectasia. Case report].

The article describes a rare clinical case of the patient with pulmonary hypertension associated with hereditary hemorrhagic telangiectasia and discusses the issues of the treatment choice of these patients. The presented clinical case is of interest because pulmonary hypertension was initially revealed, then its hereditary nature was confirmed and OslerWeberRendu disease was diagnosed.

[Chronic thromboembolic pulmonary hypertension: from pathogenesis to the choice of treatment tactics].

Presents data on the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH), which serve as a rationale for approaches to the choice of treatment. CTEPH usually begins with persistent obstruction of the large and/or medium pulmonary arteries by organized thrombi. Impaired lysis of thrombi may be associated with abnormal fibrinolysis, hematological or autoimmune diseases. The molecular processes underlying the lesions of small vessels are not fully understand. The degree of small-vessel disease has a significant impact on the severity of CTEPH and postoperative outcomes. The CTEPH treatment has evolved with the development of three directions pulmonary endarterectomy, balloon angioplasty of pulmonary arteries and the use of specific therapy used for pulmonary arterial hypertension. The paper demonstrates the possibilities of a multimodal approach in the treatment of this category of patients.

[Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases]. / Koaguliatsionnaia aktivnost' tsirkuliruiushchikh membrannykh mikrochastits u patsientov s serdechno-sosudistymi zabolevaniiami.

Membrane microparticles (MP) are released by activated or damaged cells and are able to accelerate blood clotting (coagulation). MP possess coagulation activity since all of them contain on their surface phosphatidylserine (PS), a substrate for the assembly of coagulation complexes, and some of them tissue factor (TF), the primary initiator of coagulation cascade reactions. We compared the coagulation activity and amount of MP in the blood of healthy donors (n=34) and patients with myocardial infarction (MI) (n=32), advanced atherosclerosis (AA) (n=32) and idiopathic pulmonary arterial hypertension (IPAH) (n=19). Total MP fraction was obtained from blood plasma by sedimentation at 20000 g, 30 min. The coagulation activity of PM isolated from 100 µl of donor and patient plasma was determined using a modified recalcification test. MP were added to substrate plasma devoid of endogenous MF, plasma was recalcified, and clotting was recorded by changes in optical density (A450), determining lag phase (min) and maximum rate (Vmax, %A450/min). MP were counted by flow cytometry as PS+ particles (lactadgerin-FITC staining) smaller than 1 µm and their concentration was expressed as 105 MP/µl plasma. MP in all patient groups accelerated plasma clotting more effectively than donor MP. Lag phase compared with donors (11.8 [11.0-13.1] median and interquartile range) was shorter in patients with AA (8.8 [7.0-10.3], p.

Case report of mild form of a new coronavirus infection in patient with idiopathic pulmonary hypertension.

The article presents a clinical case of mild novel coronavirus infection COVID-19 complicated with bilateral interstitial pneumonia in a female patient with idiopathic pulmonary hypertension.

[Possibilities of Magnetic Resonance Tomography in Diagnosis of Pulmonary Arterial Hypertension].

The emergence of more effective methods for treatment of pulmonary arterial hypertension (PAH) has called for more reliable methods of diagnostics, monitoring, and evaluating responses to the treatment. More reports have become available about the relevance of using magnetic resonance imaging (MRI) for examination of patients with PAH. This review provides data on the significance of MRI for noninvasive evaluation of the heart structure and function in patients with PAH, as well as for visualization and evaluation of the remodeling of the pulmonary circulation. According to the data presented in this review, the results obtained with various, modern MRI technologies can be used for monitoring the effect of treatment and for risk stratification in patients with PAH.

[Influence of demographic characteristics on the clinical course and results of therapy in patients with precapillary pulmonary hypertension].

AIM: To assess the clinical course of the disease and the features of the treatment goals achievement in patients with IPAH and inoperable CTEPH depending on gender and age at the time of diagnosis verification. MATERIALS AND METHODS: The study included 88 patients with IPAH and 38 patients with inoperable CTEPH with a PAWP 12 mm Hg and the duration of PAH-specific therapy treatment more than 12 months. IPAH/CTEPH patients were divided into groups depending on age at the time of diagnosis verification: age 50 years (n=69)/ 50 years (n=57), and gender: 106 women/20 men. RESULTS: Patients with age 50 years at the time of diagnosis verification have significantly more severe functional class (WHO). In IPAH/CTEPH male patients a significant hemodynamic disorder also as significantly higher level of NT-proBNP at the time of diagnosis verification were observed. In men with IPAH/CTEPH and patients aged 50 years more pronounced deterioration of right ventricular systolic function was observed (ECHO). Patients with IPAH younger than 50 years were significantly more likely to achieve the treatment goals by the median 26.5 months of treatment compared to the patients aged 50 years (21% vs 6.45%). Men with IPAH/CTEPH were significantly more likely to have a high risk of death (90%) at baseline compared to the women (61%). CONCLUSION: IPAH/inoperable CTEPH patients with male sex, as well as the age 50 years and older at the time of diagnosis verification, compared with younger ones, are associated with a less favorable course of the disease.

[Impact of summer heat waves on key parameters of oxidative stress in patients with coronary artery disease].

AIM: To assess the impact of summer heat waves on key parameters of oxidative stress in patients with coronary heart disease. MATERIALS AND METHODS: We included 30 male patients aged 5213 years with stable angina pectoris of IIIII functional class with at least one coronary artery stenosis proved by angiography (ischemic group) in comparison with 10 male patients aged 487 years with no angiographic sings of significant coronary stenosis and without angina manifestation (non-ischemic group). The following parameters were studied: activity of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), the level of malondialdehyde (MDA) and MDA-modified low-density lipoproteins (MDA-LDL). The analysis of indicators was performed at normal average daily temperature (daytime temperature not higher than 20С) and after a heat wave (daytime temperature above 27C for more than 2 consecutive days). RESULTS: Our study revealed the decrease of CAT and GSH-Px activities with increased activity of Cu,Zn-SOD in both groups after the heat wave. At the same time we observed accumulation of MDA and increased MDA-LDL level in both groups. Initially ischemic patients showed significantly increased level of CAT and GSH-Px activity compared to the non-ischemic group, while it was no difference in activity of Cu,Zn-SOD and MDA and MDA-LDL level. We observed significant reduce of Cu,Zn-SOD activity in ischemic patients compared to non-ischemic group with no significant differences in all other studied parameters of oxidative stress after heat wave. CONCLUSION: Changes in the key parameters of oxidative stress in patients with ischemic heart disease during summer heat waves are comparable to those in patients without ischemia, however significantly greater inhibition of GSH-Px activity and significantly lower increase in Cu,Zn-SOD activity was noted. These results may indicate misregulation of free radical processes in patients with ischemic heart decease.

[Pulmonary arterial hypertension: achievements and realities of modern treatment, a look into the future].

The paper summarizes the most important aspects of modern treatment of patients with pulmonary arterial hypertension (PAH): the goals of therapy are indicated, the issues of risk stratification of PAH progression/mortality, the place of combination specific therapy and switching strategies are considered, as well as new promising approaches to therapy; features of the course of the new coronavirus infection COVID-19 in this category of patients are discussed.

[Characteristics of patients with chronic thromboembolic pulmonary hypertension according to the Russian National Registry].

AIM: To assess demographic and clinical characteristics, to describe of the functional and hemodynamic status, profile of concomitant pathology, data of instrumental examination in chronic thromboembolic pulmonary hypertension (CTEPH) patients; to study the features of specific and supportive therapy according to the data of the Russian national registry. MATERIALS AND METHODS: From 2012 till 2020 a multicenter, prospective study in 15 regional expert centers of the Russian Federation (www.medibase.pro) included 404 newly diagnosed CTEPH patients over the age of 18 years in the Russian registry of patients with pulmonary arterial hypertension and CTEPH (NCT03707561). The diagnosis was established by European and Russian clinical guidelines for the diagnosis and management of pulmonary hypertension. 154 inoperable CTEPH patients an additional analysis of specific and supportive therapy was performed. RESULTS: The study included 404 patients (55.6% women and 44.3% men) at the age of 58.6 [48.6; 69.3] years. Median time from symptom onset to the diagnosis verification waswas 2.4 years (from 0.1 to 2.9 years). 79.1% of patients were in the III and IV functional class (World Health Organization) at the time of diagnosis and in 44.1% with RHF (right heart failure). In assessing the profile of concomitant pathology, it was noted that CTEPH patients were more often with arterial hypertension (39.1%), erosive-ulcerative lesions of the stomach/duodenum (16.1%), atrial fibrillation (13.8%), obesity (13.1%). Distance in 6MWD (6-min walk distance) was 337.2 [250; 422] m, Borg dyspnea index scale 4.1 [3.0; 5.0] points. Hemodynamic parameters according to right heart catheterization were: Mean PAP (pulmonary arterial pressure) (51.114.04) mmHg, CO (cardiac output) (3.50.98) l/min, CI (cardiac index) (2.00.48) l/min/m2, PVR (2008528) dyns/cm5. CONCLUSION: According to the Russian registry, inoperable CTEPH patients had precapillary PH (pulmonary hypertension) with severe functional status, in combination with frequent concomitant pathology (arterial hypertension, erosive-ulcerative lesions of the stomach/duodenum, atrial fibrillation, obesity, right heart failure). 66% of inoperable CTEPH patients received specific drug therapy.

[Optimization of specific therapy for pulmonary hypertension: the possibilities of riociguat].

Pulmonary hypertension (PH) is a severe and often rapidly progressive disease with fatal outcome. Endothelial dysfunction in PH is associated with decreased nitric oxide production. After reviewing the mechanisms of action and the evidence base for specific therapy with phosphodiesterase 5 inhibitors (PDE-5) and soluble guanylate cyclase stimulators, a reseach review on switching from PDE-5 to riociguat is conducted. A potential advantage of riociguat is its independence from endogenous nitric oxide and from the other (besides PDE-5) isoenzymes of phosphodiesterases. The favorable efficacy profile of sildenafil has been proven for the main forms of pulmonary arterial hypertension, of riociguat for the main forms of pulmonary arterial hypertension and chronic thromboembolic PH. The clinical efficacy of replacing PDE-5 with riociguat has been demonstrated in uncontrolled trials and in the randomized controlled study REPLACE. The possibility of therapy optimization by switching from IFDE-5 to riociguat is fixed in the Russian (class and level of evidence B-3) and Eurasian (class and level of evidence IIb-B) clinical guidelines, as well as in the materials of the Cologne Expert Consensus. An additional argument for switching is the lower cost as compared to combination therapy in the Russian Federation. According to the Russian and Eurasian guidelines for PH and the Russian instructions for the use of riociguat, the drug should be taken at least 24 hours after sildenafil discontinuation.

[Problematic aspects of pulmonary hypertension due to left heart disease: focus on combined postcapillary and precapillary pulmonary hypertension].

Рulmonary hypertension (PH) is a common complication of left heart diseases. In addition to a passive increase of pressure in the venous bed of the pulmonary circulation, leading to an increase of mean pulmonary pressure, signs of precapillary PH could be detected in some patients. Since 2013, a hemodynamic subtype of PH due to left heart diseases combined post/precapillary PH has been identified, with a more unfavorable prognosis and high mortality.

[The achievements of the modern specific therapy of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: focus on the stimulator of soluble guanylate cyclase riociguat].

Currently, treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is focused on three signaling pathways: the NO pathway, the endothelin pathway, and the prostacyclin pathway. Riociguat is the only representative of stimulators of the soluble guanylate cyclase (sGC) class that is approved for the treatment of PAH and inoperable and persistent/recurrent CTEPH. The review presents data from clinical trials showing a positive effect of riociguat on the functional and hemodynamic profile of patients with PAH and CTEPH. In recent years there has been much discussion about the possibility of optimizing therapy by switching to drugs that affect a single pathogenesis target. Thus, sGC stimulants have obvious advantages over phosphodiesterase type 5 (PDE-5) inhibitors, including the ability of riociguat to exert pharmacological effects (due to a NO-independent mechanism of action) even in conditions of reduced NO production. Switching from PDE-5 to riociguat may be safe and appropriate, according to clinical trials presented in the review. In accordance with the guidelines for the diagnosis and treatment of pulmonary hypertension of the Eurasian Association of cardiologists from 2019, this strategy is approved when PDE5 therapy is ineffective in patients with PAH FC III (WHO).

[Dynamics of the clinical functional and hemodynamic profile of patients with pulmonary arterial hypertension with initial monotherapy with endothelin receptor antagonists: bosentan vs. macitentan].

Aim To compare results of 24-h treatments with bosentan and macitentan by the clinical functional status and indexes of pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH).Materials and methods Based on the Russian National Registry (NCT03707561), 44 patients older than 18 years with PAH (34 patients with idiopathic pulmonary hypertension (IPH) and 10 patients with Eisenmenger syndrome) were retrospectively included into this study. Based on the statistical method of pairwise comparison, two groups were formed and matched by age, gender, WHO functional class (FC), and 6-min walk distance (6MWD). 22 patients of group 1 (17 with IPH and 5 with Eisenmenger syndrome) were treated with macitentan 10 mg/day, and 22 patients of group 2 (17 with IPH and 5 with Eisenmenger syndrome) were treated with bosentan 250 mg/day. Clinical instrumental data (6MWD, Borg dyspnea score, chest X-ray, transthoracic echocardiography (EchoCG), and right heart catheterization (RHC)) were evaluated at baseline and after 24 weeks of therapy.Results By week 24 of the treatment, FC and 6MWD improved in both groups. The macitentan treatment was associated with a significant decrease in Borg score. Significant intergroup differences in EchoCG data were not observed. The bosentan treatment was associated with a decrease in right ventricular (RV) dimension and a tendency towards a decrease in calculated pulmonary artery systolic pressure (PASP). By week 24, the macitentan treatment as compared to the bosentan treatment, was associated with a decrease in cardiothoracic ratio (CTR). In both groups, RHC showed decreases in PASP, mean pulmonary artery pressure and pulmonary vascular resistance, and improvements in cardiac output (CO), cardiac index, and stroke volume (SV) values. By week 24, the increase in SV was greater in the macitentan treatment group than in the bosentan treatment group (р=0.05).Conclusion The 24-week treatment with bosentan or macitentan provided significant and comparable improvement of the functional profile in PAH patients with FC II (WHO) at baseline. The decrease in CTR was significantly more pronounced in the macitental treatment group compared to the bosentan treatment group. The 24-week bosentan treatment resulted in a decrease in RV anterior-posterior dimension, a tendency towards a decrease in PASP according to EchoCG data. Macitentan provided more pronounced dynamics of dyspnea than bosentan according to the results of 6MWD test and the increase in SV according to RHC data.

[The soluble guanylate cyclase stimulator riociguat is the first-line therapy for chronic thromboembolic pulmonary hypertension patients].

Chronic thromboembolic pulmonary hypertension (CTEPH) is a precapillary type of pulmonary hypertension with chronic obstruction of large and medium branches of pulmonary arteries along with secondary alterations in pulmonary microcirculation, which cause progressive increases in pulmonary vascular resistance and pulmonary arterial pressure and ensuing severe right heart dysfunction and heart failure. Pulmonary thromboendarterectomy (PTE) is the treatment of choice for CTEPH; however, this procedure is available not for all patients. Although the surgery performed in the conditions of centers with advanced experience generally shows good results, up to 40% of patients are technically inoperable or PTE is associated with a high risk of complications. At present, riociguat, the only officially approved drug from the class of soluble guanylate cyclase stimulators, is considered as a first-line treatment for inoperable and residual forms of STEPH. Introduction of riociguat to clinical practice can be called a real breakthrough in the treatment of patients with STEPH who cannot undergo PTE or those with relapse or persistent STEPH after the surgery.

[Socio-economic burden of pulmonary hypertension: relevance of assessment in Russia and the world].

Pulmonary hypertension (PH) is a progressive disease which is characterized with the increase of pulmonary artery pressure and pulmonary vascular resistance. Such condition leads to right ventricular heart failure and premature death of patients. Pulmonary arterial hypertension (PAH) has the status of an orphan disease. However in Russia only idiopathic PH is included in the list of 24 life-threatening and chronic progressive rare diseases, while other forms of PH are not in it. Inclusion in this list guarantees drug provision for patients at the expense of the regional budget, while patients with other forms of PH can rely on free medication only if they have a disability. The lack of criteria for revising this list as well as the imperfection of legal regulation in the field of drug support for orphan diseases leads to high disability, a significant decrease in the duration and quality of life of patients with PH. As part of a multicriteria approach, a clinical and economic analysis of the disease burden can be one of the tools for policy development and decision-making on the distribution of funding in the healthcare. The article provides a review of the economic burden of various forms of PH in the world.

Pulmonary arterial hypertension in Russia: six-year observation analysis of the National Registry.

AIM: Assess the prevalence, clinical course, current therapy, and mortality in patients with pulmonary arterial hypertension (PAH) in the National Registry. MATERIALS AND METHODS: In the prospective study we included patients over 18 years of age with diagnosed PAH [idiopathic PAH (IPAH); Drug- and Toxin-Induced Pulmonary Hypertension; inherited PAH; PAH associated with congenital heart disease (PAH-CHD); PAH associated with systemic connective tissue disease (PAH-CTD); PAH associated with HIV infection (PAH-HIV); with portal pulmonary hypertension (portoPAH)]. The observation was carried out in 15 expert centers of Russia from 01.01.2012 to 31.12.2017. RESULTS: Our registry included 470 patients with PAH: IPAH - 41.5%, PAH-CHD - 36%, PAH-CTD - 19.5%, inherited PAH - 0.4%, portoPAH - 1.9%, PAH-HIV - 0.4%, Drug- and Toxin-Induced PAH - 0.4%. The prevalence among women was 84%. The mean age at the time of patient enrollment in the registry for the overall group of PAH was 42.7±15.3 years. The distance in the 6-minute walking test was 361.3±129.3 m. Among all patients with PAH, 65% had functional class (FC) III/IV at the time of diagnosis, among IPAH - 62%. 69.9% received PAH-specific therapy, of which 62.1% - monotherapy, 32.7% - dual combination therapy, and 5.2% triple therapy. Sildenafil is the most commonly prescribed drug in the regimen of monotherapy. 31.6% of patients were treated with bosentan, 6.4% - riociguat, 3.4% - ambrisentan, 2.1% - macitentan and 2.0% iloprost. Survival of patients with PAH was 98.9% at 1 year of follow-up, 94.1% at 3 years and 86.0% at 5 years. CONCLUSION: The registry data indirectly indicates the need to increase efforts aimed at improving the diagnosis of systemic connective tissue diseases in adults, as well as congenital heart defects in children for timely surgical treatment. In recent years, PAH-specific drugs of the new generation have been introduced into clinical practice, but currently in Russia there are no parenteral prostanoids, which are recommended for the most severe patients.

[Features of clinical, functional and hemodynamics profile, medical treatment and prognosis evaluation in patients with inoperable chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension according to the Russian registry].

AIM: to perform the complex analysis of clinical, functional, hemodynamics profile in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) compared to the idiopathic pulmonary arterial hypertension (IPAH) group at the time of diagnosis verification according to the Russian registry, and to evaluate the features of medical therapy and it's influence on prognosis in these patients. MATERIALS AND METHODS: In the retrospective study 193 patients with IPAH and 130 patients with inoperable CTEPH older than 18 years were included. All included patients were the participants of Russian registry (www.medibase.pro) in 15 Russian expert centers during the period from 01.01.2012 to 31.12.2018 year. The diagnosis was verified according to the algorithm, reflected in the Russian guidelines on diagnosis and treatment of PH and CTEPH (2016 year). The comparison analysis of clinical, functional, hemodynamics parameters in patients with IPAH and inoperable CTEPH was made. RESULTS: The status of 193 patients with IPAH (32 male and 162 female) and 130 patients with inoperable CTEPH - (40 male and 90 female) was analyzed during the study. The CTEPH patients were older compared to the IPAH patients: 52.2 [41.1; 60.6] and 36.5 [26.8; 36.5] years, respectively. The median period since symptom occurrence till CTEPH verification was 1.08 [0.2; 3.1] years, in IPAH patients - 2.01 [0.6; 4.2] years. More than 80% of inoperable CTEPH patients had III and IV functional class (FC) according to the World Health Organization classification at the time of diagnosis verification versus 61% of IPAH patients. According to echocardiography the level of mean pulmonary arterial pressure was comparable in two groups of PH patients. However in inoperable CTEPH patients the right atrial area was larger. The significantly higher value of mean pulmonary arterial pressure and lower value oxygen saturation of arterial blood according to the right heart catheterization were revealed. The 5-year survival in CTEPH patients, receiving initial dual combination therapy in 75% cases (in 40% - combination of riociguat and iloprost ) was 93% versus 86.5% in patients with IPAH. CONCLUSION: It was revealed, that inoperable CTEPH patients were significantly older with severe functional and hemodynamics status at the time of diagnosis verification, although with higher level of 5-year survival compared to the IPAH patients according to the Russian registry.