INVESTIGATION OF CENTRAL HEMODYNAMICS VIA RIGHT HEART AND PULMONARY ARTERY CATHETERIZATION IN PATIENTS WITH SYSTEMIC CONNECTIVE TISSUE DISEASES

Pulmonary arterial hypertension (PAH) associated with systemic connective tissue diseases (SCTD) is a poor prognostic manifestation of the latter that result in death if untreated. The invasive determination of hemodynamic parameters is prominent in diagnosing the disease and determining its treatment policy and prognosis.Objective: to analyze the results of catheterization in PAH-SCTD patients admitted to the V.A. Nasonova Research Institute of Rheumatology.Subjects and methods. The investigation included 59 patients admitted to the V.A. Nasonova Research Institute of Rheumatology from September 2009 to September 2014. PAH was diagnosed in accordance with the conventional guidelines. All the patients underwent right heart and pulmonary artery (PA) catheterization at the diagnosis and over time during treatment.Results and discussion. All the patients included in the trial met the pre-capillary pulmonary hypertension (PH) criteria: mean pulmonary artery pressure (MPAP) ≥25 mm Hg; and PA wedge pressure (PAWP) <15 mm Hg. The exclusion of other causes of PH (pulmonary fibrosis, left heart disease, and thromboembolism), as well as a high transpulmonary pressure gradient >15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units could diagnose PAH in all our patients. There was a statistically highly significant association between pathological hemodynamic changes and functional class (FC). FC was found to be most closely correlated with right atrial pressure (RAP), cardiac output (CO), PVR, and cardiac index (CI). Among the most common manifestations of heart failure, only the presence of peripheral edemas was associated with worse hemodynamic parameters in PAH. It should be noted that out of two biomarkers (N-terminal pro-brain natriuretic peptide and uric acid), the former is largely related to the magnitude of changes in hemodynamic factors. The critical values of hemodynamic parameters were due to extreme edema – anasarca (RAP >17 mm Hg, PVR >20 Wood units, CI <14 ml/m2). Analysis of clinical and instrumental parameters in relation to FC revealed a linear relationship of RAP, CO, and PVR between the level of these parameters and FC; moreover, the highest correlation coefficients were observed for the hemodynamic parameters characterizing right ventricular systolic function. It is remarkable that no MPAP changes were found; only patients with FC IV showed its slight increase (from 51±8 to 55±8 mm Hg; р = 0.087). PAWP remained unchanged regardless of FC. Conclusion. Thus, the hemodynamic parameters determined in patients with PAH-SCTD during right heart and LA catheterization are closely related to the manifestations of respiratory and heart failure, the biomarkers, and FC of PAH

Внутривенный илопрост в комплексной терапии сосудистых нарушений у пациентов с системными заболеваниями соединительной ткани

Systemic connective tissue diseases, systemic scleroderma in particular, constitute a group of diseases in which vascular disorders underlying diverse clinical manifestations are one of the pathogenetic components. Raynaud 's syndrome and ulceration are the most common symptoms of these diseases, which influence quality of life in patients and require constant drug therapy. The paper discusses the authors' clinical experience with intravenous iloprost used in the combination therapy of the vascular manifestations of systemic scleroderma and systemic lupus erythematosus.Системные заболевания соединительной ткани, в частности системная склеродермия, представляют собой группу болезней, при которых одним из патогенетических звеньев являются сосудистые нарушения, лежащие в основе разнообразных клинических проявлений. Синдром Рейно и образование язв — наиболее частые симптомы этих заболеваний, влияющие на качество жизни пациентов и требующие постоянной лекарственной терапии. В статье обсуждается собственный клинический опыт использования внутривенного илопроста в комплексной терапии сосудистых проявлений системной склеродермии и системной красной волчанки

ASSESSMENT OF THE IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATIC DISEASES

Objective: to investigate the immunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatic diseases (RD).Subjects and methods. The prospective open-label comparative study enrolled 133 people (102 (76.7%) women and 31 (23.3%) men) aged 23 to 76 years, including 79 patients with rheumatoid arthritis (RA), 16 with systemic sclerosis, and 7 with dermatomyositis/polymyositis, as well as 31 subjects without systemic inflammatory RD (a control group), who had a recent history of at least two cases of lower respiratory tract infections (bronchitis, pneumonia). At their inclusion, all the patients with RD were receiving ant-inflammatory therapy, including 52 taking methotrexate (MT), 14 – leflunomide (LEF), and 13 – MT + tumor necrosis factor-α (TNF-α) inhibitors. The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patients and conventional laboratory studies were performed during control visits (1, 3, and 12 months after vaccination). The serum levels of anti-pneumococcal capsular polysaccharide antibodies were measured in 102 patients by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, United Kingdom).Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period of 12 months. The patients with RD and the control group showed a significant, more than double increase in anti-pneumococcal antibodies 12 months following vaccination. Vaccination was well tolerated: 90 (68%) patients displayed no adverse events; 37 (28%) had pain, cutaneous swelling and hyperemia up to 2 cm in diameter at the site of injection for vaccination;6 (4%) had low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD

Intravenous iloprost in the combination therapy of vascular disorders in patients with systemic connective tissue diseases

Systemic connective tissue diseases, systemic scleroderma in particular, constitute a group of diseases in which vascular disorders underlying diverse clinical manifestations are one of the pathogenetic components. Raynaud 's syndrome and ulceration are the most common symptoms of these diseases, which influence quality of life in patients and require constant drug therapy. The paper discusses the authors' clinical experience with intravenous iloprost used in the combination therapy of the vascular manifestations of systemic scleroderma and systemic lupus erythematosus

UP-FRONT TRIPLE COMBINATION THERAPY FOR PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH SYSTEMIC SCLEROSIS: A CASE REPORT

Pulmonary arterial hypertension (PAH) is a progressive and irreversible disease characterized by a steady increase in pulmonary vascular resistance (PVR) and death. Introduction of current PAH-specific drugs has not solved the problem of follow-up of critical patients with PAH associated with systemic sclerosis (SSc). Clinical trials have shown that 1-, 2- and 3-year survival rates are 77, 46, and 33%, respectively. Arguments in favor of starting triple PAH-specific therapy that substantially improves the prognosis of this critical group of patients are being accumulated. The paper describes Russia’s first clinical case of successful up-front triple combination therapy (iloprost, bosentan and sildenafil) in a 40 year old female with SSc and diagnosed functional class (FC) IV PAH. There were clinical, laboratory, and hemodynamic improvements already at 2 weeks after therapy initiation. Thirty-month therapy resulted in a reversal of FC from IV to II, relieved the signs of right ventricular failure, complete right ventricular reverse remodeling and subnormalization of hemodynamic parameters. Hemodynamic improvement including reductions in right atrial pressure to 4 mm Hg, mean pulmonary arterial pressure to 26 mm Hg, and PVR to 2.2 Wood units and an increase in cardiac output up to 7.4 l/min, despite preserved elevated uric acid levels (432 μmol/l). The intriguing feature of this case is critically low values of % predicted/carbon monoxide lung diffusion capacity, which rose from 17% to only 22%, in the presence of positive changes. This clinical case demonstrates the predictive capabilities of up-front triple combination therapy for severe PAH associated with SSc

The first Russian experience with the endothelin 1 receptor inhibitor traclir used in patients with pulmonary hypertension associated with systemic connective tissue diseases

Objective: to study the efficacy and safety of the endothelin 1 receptor inhibitor traclir in patients with pulmonary hypertension (PH) asso ciated with systemic connective tissue diseases. Subjects and methods. The study included 4 patients: 3 with scleroderma systematica and 1 with exanthematous lupus erythematosus. The diagnosis of PH was established on the basis of right heart catheterization data and after exclusion of all its other causes of HP. In addition to hemodynamic evaluation, the female patients underwent echocardiography (EchoCG), lung function tests, 6-minute walk test, and blood biochemical study (determination of uric acid levels). Traclir was given in a dose of 62.5 mg twice in the first 4 weeks of the study and then in a dose of 125 mg twice for the subsequent 12 weeks. Every 4 weeks, the levels of transaminases were monitored and a pregnancy test was carried out in patients of fertile age. Results. After 16-week intake of the drug, all the female patients were found to have obvious positive changes as a longer 6-min walk test distance and two female patients had improvement in the functional class of PH. Estimation of hemodynamic parameters suggested a posi tive effect in all the female patients, as confirmed primarily by an increase in cardiac index and a reduction in pulmonary vascular resist ance. According to EchoCG data, there was a substantial increase in tricuspid annular plane systolic excursion; other parameters had no informative value. During traclir therapy, there was also an increase in lung diffusion capacity and a reduction in uric acid levels. There were no adverse events throughout the trial. Conclusion. Thus, the experience with traclir used in patients with PH associated with systemic autoimmune diseases suggests its high effi cacy and safety

POSSIBILITIES FOR ECHOCARDIOGRAPHIC DETERMINATION OF PULMONARY ARTERY PRESSURE IN PATIENTS WITH SYSTEMIC CONNECTIVE TISSUE DISEASES: DATA OF A RHEUMATOLOGY EXPERT CENTER

Objective: to assess the significance of noninvasive estimation of pulmonary artery pressure (PAP) using Doppler echocardiography (echoCG) as compared to invasive measurements of this parameter in patients with systemic connective tissue diseases (SCTD). Subjects and methods. The invasively measured hemodynamic parameters versus those estimated at echoCG were analyzed. The analysis included 156 paired studies of 61 patients with pulmonary hypertension (PH) in the presence of SCTD and 26 patients, in whom PH was not verified by catheterization. Forty-five patients were found to have PH; PH was caused by left heart involvement in 7 patients and by hypoxemia in 9. Results and discussion. Systolic PAP (SPAP) measured by echoCG averaged 72.4±33.7 mm Hg and that by right heart catheterization did 63.3±25.1 mm Hg. The correlation of the values of this measure, which were obtained by the two methods, was highly significant (r = 0.83; p < 0.00001). Right atrial pressure (RAP) measured by echoCG and catheterization was 8.4±4.1 and 6.7±5.2 mm Hg, respectively. The echoCG and catheterization RAP correlation was highly significant (r = 0.57; p < 0.0001). Despite the high correlation coefficients, echoCG failed to detect higher SPAP in 7 patients with PH verified by catheterization; EchoCG could not detect higher SPAP; false-positive results were absent. EchoCG demonstrated good sensitivity (94%) and specificity (100%) for a threshold SPAP of 40.1 mm Hg (the area under the curve was 0.99 (p < 0.0001) with 95% CI 0.98–1.01. The echoCG determination of RAP by the existing methods showed good sensitivity (79%) and specificity (69%) for its threshold of 5 mm Hg (the area under the curve was 0.79 (p < 0.0001) with 95% CI 0.70–0.95. The patients with low level of mean PAP (PAPmean) measured by catheterization showed a difference of > 10 mm Hg as compared with the echoCG levels in 5% of the cases; > 20 mm Hg discrepancy was not noted. In patients with high PAPmean, the differences of > 10 and > 20 mm Hg were observed in 28.9 and 34.2% of the cases, respectively. Analysis of the Bland–Altman agreement showed deviations of +8.22 mm Hg for SPAP (95% CI 6.6–12.8) and +1.56 mm Hg for RAP (95% CI 0.85–2.27). The standard deviation of differences was 18.4 for SPAP and 4.5 for RAP. There was a relationship between the differences from their mean value, which is more significant for SPAP. The correlation coefficient for SPAP was 0.43 (p < 0.001) and that for RAP was 0.31 (p < 0.05). Thus, the Bland–Altman analysis revealed a systematic disparity, suggesting a weak agreement of the results of the two methods determining SPAP and RAP. Conclusion. Our investigation demonstrated that echoCG proved to be a valid and reliable screening method for PH in patients with SCTD. More accurate estimation of SPAP and RAP measurement requires the application of invasive diagnostic methods