[Hemodynamic Predictors of Clinical Deterioration in Patients With Pulmonary Arterial Hypertension Associated With Systemic Scleroderma].

OBJECTIVE: to elucidate hemodynamic predictors of clinical deterioration (CD) in patients with pulmonary arterial hypertension (PAH) associated with systemic scleroderma (SSD). MATERIAL AND METHODS: We included into this study 48 patients with PAH-SSD consecutively admitted in 2004-2014. At inclusion all patients underwent right heart catheterization (RHC) and thereafter were under dynamic observation. CD deterioration was diagnosed in the presence of the following: >15% decline in 6-minute walk test distance; worsening of PAH functional class; intensification of symptoms of right ventricular failure; necessity in administration of parenteral diuretics. RHC was used for confirmation of CD. Relative risk (RR) of events was calculated for identification of significant predictors of CD. Cut points were determined with the help of construction of characteristic curves, statistical significance was estimated in Kaplan-Meier analysis. RESULTS: During follow-up (duration 46 [23;91] months) 21 patients had 24 CDs confirmed by RHC. Calculation of RR identified a number of hemodynamic parameters related to CD development. ROC analysis confirmed significance of initial right atrial pressure (RAP) 6.5 mm Hg (95% confidence interval [CI] 0.59-0.89, sensitivity 71%, specificity 63%, p<0.004) and dynamics of pulmonary vascular resistance (PVR) -1.06 Wood units (95%CI 0.790.99; sensitivity 76%, specificity 80%, <0.0001). Kaplan-Meier analysis revealed significant differences in times to CD (median 31.5 and 10 months in patients with RAP <6.5 and more or equal 6.5 mm Hg, respectively, p=0.01; 37 and 17months in patients with PVR lowering >1.06 Wood units and no PVR lowering, respectively, p=0.009. CONCLUSION: We identified prognostic levels of key hemodynamic predictors of CD in patients with SSD and PAH (RAP 6.5 mm Hg, PVR - 1. 06 Wood units) which can be used for individualization and optimization of therapy.

[Clinical and hemodynamic characteristics and possibilities for therapy in patients with severe (functional class IV) pulmonary arterial hypertension associated with diffuse connective tissue diseases].

AIM: To study the clinical and hemodynamic characteristics of a group of patients with Functional Class (FC) IV pulmonary arterial hypertension (PAH) developing in the presence of diffuse connective tissue diseases (DCTD) and to evaluate the efficacy of intravenous iloprost. SUBJECTS AND METHODS: The study enrolled 59 patients with PAN-DCTD, including 7 who had FC IV and 8 who developed this condition during a follow-up. The diagnosis of PAH was based on pulmonary artery catheterization findings. FC IV was diagnosed using the conventional New York Heart Association classification. All the patients received PAH-specific therapy (bosentan, sildenafil); the patients with FC IV had combined therapy; 4 patients were treated with intravenous iloprost calculated with reference to 0.5-2.5 ng/kg/min for 15 days. In addition to the patients with FC IV, 3 patients with unstable FC Ill were given iloprost. Besides targeted therapy, all the patients received standard treatment, including diuretics, and ionotropic therapy. RESULTS: Evaluation of hemodynamics in patients with different FCs revealed the most important differences in right atrial pressure, cardiac output, cardiac index, and pulmonary vascular resistance. A linear relationship was seen between the level of this indicator and FC, the closest correlation being for hemodynamic parameters characterizing right ventricular systolic function. There were no changes in mean pulmonary artery pressure; only the patients with FC IV were found to have its slight elevation (from 52 ± 15 to 55 ± 11 mm Hg). Pulmonary artery wedge pressure remained unchanged regardless of FC. Intravenous iloprost was noted to have an obvious positive effect on both clinical and hemodynamic parameters. Catheterization verified improvement in 6 out of the 7 patients; no hemodynamic changes were found in 1 patient during 15-day therapy. CONCLUSION: The patients with FC IV PAH-DCTD have clinical and hemodynamic features responsible for a fatal prognosis. The results of using intravenous iloprost in patients with decompensated PAH associated with scleroderma systematica convince to use its PAH-specific tablets in cases of verified clinical deterioration when taking its dosage form.

[Impact of bosentan therapy on stress-induced pulmonary hypertension in patients with systemic sclerosis].

AIM: To describe hemodynamic and clinical changes in patients with elevated mean pulmonary artery pressure (MPAP) > 30 mm Hg during exercise and the impact of bosentan therapy on stress-induced pulmonary hypertension (SIPH). SUBJECTS AND METHODS: The study included 19 patients with systemic sclerosis (SDS) in whom possible causes of pulmonary hypertension (PH) (lung and left heart injuries and thromboembolism) were excluded. All the patients underwent pulmonary artery catheterization at rest and during exercise. The hemodynamic (right atrial pressure (RAP), systolic and diastolic pressure, MPAP, pulmonary artery wedge pressure (PAWP), cardiac output (CO) by a thermodilution technique), clinical (demographic, immunological, and instrumental) parameters were analyzed and the risk of pulmonary arterial hypertension (PAH) was also calculated; 5 patients with SIPH received 16-week bosentan therapy according to the conventional regimen. RESULTS: Ten of the 19 patients were at increased risk for PAH in accordance with the DETECT scale, but no signs of PH at resting catheterization were found in anybody. In 5 patients, MPAP, was in the range from 21 to 24 mm Hg; in 9 (47%) patients were found to have SIPH, a median MPAP of 35 (32; 41) mm Hg. Seven patients had no diagnostic changes during exercise; 3 patients could not perform an exercise test. There were correlations between MPAP and DETECT risk scores (p < 0.05). The patients with SIPH had significantly higher levels of resting MPAP and exercise pulmonary vascular resistance (PVR) and PAWP. The calculated DETECT risk was significantly higher in the SIPH group. The level of uric acid was also higher in the SIPH group (p < 0.05). There were no changes in NT-proBNP levels, telangiectasias and anti-centromere antibodies, and EchoCG and lung test results. During 16-week bosentan therapy, there was a significant decrease in MPAP and transpulmonary gradient during exercise, but PVR, MPAP/CO ratio and NT-proBNP levels tended to decrease. CONCLUSION: In the patients with SDS, SIPH may be a stage of pulmonary vasculopathy that precedes the development of clinical PAH. The use of current PAH-specific drugs used at the preclinical stage of the disease may substantially improve lifetime prognosis in patients with SDS-associated PAH.

[Survival in pulmonary arterial hypertension, associated with connective tissue diseases, treated by sildenafil: results of the prospective study].

AIM: To investigate the effect of sildenafil on the survival of patients with pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD), who have been followed up at the Rheumatology Expert Center. SUBJECTS AND METHODS: A total of 16 patients (all women) with PAH associated with CTD, who had been admitted to the V. A. Nasonova Research Institute of Rheumatology in 2013-2015, were examined. PAH corresponded to Functional Class II in the majority of the patients. After the diagnosis was verified by catheterization of the right heart and pulmonary artery, all the patients received original sildenafil (a phosphodiesterase type 5 inhibitor, a potent vasodilator, the efficiency of which was proven in patients with PAH) at a dose of 20 mg thrice daily. Survival rates and time to clinical deterioration were estimated during a prospective follow-up). RESULTS: Three-year survival rates were 94% in the study group and 25% in the group of historical control (p < 0.05). The time to clinical deterioration was associated with the duration of the follow-up and hemodynamic parameters (right atrial pressure and changes in vascular resistance within 4 months after therapy initiation). CONCLUSION: The administration of sildenafil substantially improves survival in patients with PAH associated with CTD as compared with the historical control. The identification of poor prognostic factors in this cohort of patients and early diagnosis will favor the personification of therapy for the fatal manifestation of CTD.

[Bosentan: a considerable increase in the survival of patients with pulmonary hypertension associated with systemic rheumatic diseases].

AIM: To evaluate the short-term efficacy of the nonselective endothelin receptor antagonist bosentan in the treatment of pulmonary hypertension (PH) associated with diffuse connective tissue diseases (CTD), as well as its effect on survival in both monotherapy and in combination with other PH-specific agents. SUBJECTS AND METHODS: The study included 20 CDT-associated PH patients who had been hospitalized in 2009-2013. All the patients had valid diagnoses of scleroderma systematica (SDS) (n = 18) or systemic lupus erythematosus (SLE) (n = 2). Bosentan was given in an initial dose of 62.5 mg/day twice for 4 weeks, then 125 mg/day twice. RESULTS: Eighteen patents completed therapy at 16 weeks. One patient with Functional Class (FC) IV PH associated with SDS died after 10 weeks of treatment because of PH progression; bosentan was discontinued in another patient following 4 weeks because of the enhanced activity of transaminases. The patients who had completed the investigation showed a significant FC decrease (from 2.9 +/- 1.0 to 2.4 +/- 1.0 following 16 weeks; p = 0.03), an increase in 6-minute walking distance (from 298 +/- 140 to 375 +/- 94 m; p < 0.002), a significant reduction in mean pulmonary artery pressure (from 48.2 +/- 15.0 to 42.8 +/- 12.0 mm Hg; p = 0.002), and pulmonary vascular resistance (PVR) (from 819 +/- 539 to 529 +/- 220 din/sec/cm(-5); p = 0.003). Right atrial pressure fell from 9.8 +/- 7.0 to 8.8 +/- 7.0 mm Hg; however, the changes were insignificant. There was a significant rise in cardiac index from 2.64 +/- 0.95 to 3.26 +/- 0.75 l/min/m2 (p = 0.005) and a significant decrease in uric acid levels from 562 +/- 254 to 469 +/- 194 micromol/l (p = 0.006). Overall 1-, 3-, and 5-year survival rates in patients with PH in the presence of CTD from PH onset were 100, 93, and 72%, respectively, in their treatment with endothelin receptor antagonists and differed significantly from the historical control group (87, 30, and 4%, respectively) when PH-specific therapy was unavailable. CONCLUSION: The survival of the bosentan-treated patients with SDS and PH becomes similar to that in the patients with classical SDS. Analysis of the findings revealed the association of survival with lower PVR at 16 weeks of bosentan therapy, which is indicative of the need for hemodynamic monitoring of therapeutic effectiveness.

[Prognostic value of SAPS II and APACHE II scales in patients with multiple organ failure syndrome during early postoperative period after oncological surgery]. / Prognosticheskoe znachenie shkal SAPS II i APACHE II u bol'nykh s sindromom poliorgannoi nedostatochnosti rannego posleoperatsionnogo perioda posle onkokhirurgicheskikh vmeshatel'stv.

The key fixed task was the following: detection, as soon as possible, of patients with a high risk of lethal outcome; an objective assessment of the condition of patients during the early postoperative period by using a quantitative evaluation (SAPS II, APACHE II); and defining of the prognostic value of SAPS II and APACHE II after oncology surgeries. The in-hospital lethality amounted to 53% in 73 patients with MOFS during the early postoperative period after oncology surgeries. The formalized (numerical) score, according to SAPS II and APACHE II, made it possible to detect patients with a higher risk of lethal outcome yet during the very first day after oncology surgeries. If the score of SAPS II or APACHE II topped 30 (on the first day after surgery), then the in-hospital lethality exceeded 50%. The information density of the SAPS II and APACHE II systems turned out to be identical, however, SAPS II appears to be more convenient in terms of practical usage since it demands the evolution of a smaller number of physiological parameters.