Clinical and Instrumental Characteristics of Newly Diagnosed Patients with Various Forms of Pulmonary Hypertension according to the Russian National Registry.

AIM: To study demographic and clinical characteristics and to give a comparative description of the functional and hemodynamic status, profile of concomitant pathology in patients with various forms of pulmonary arterial hypertension (PAH), and chronic thromboembolic pulmonary hypertension (CTEPH) according to the Russian National Registry. METHODS: During the period from January 01, 2012, till January 01, 2019, 1105 patients aged >18 years with verified diagnosis of PAH and CTEPH, who were subsequently observed at 15 PH expert centers of the Russian Federation in the 52 provinces, are included in the Russian registry on the basis of the Federal State Budgetary Institution of Cardiology of the Ministry of Healthcare of Russia. All newly diagnosed patients (n = 727) were entered into the registry database (NCT03707561). A comparative analysis of demographic and clinical characteristics, profile of concomitant pathology, and parameters of a comprehensive examination of patients was performed. RESULTS: Among newly diagnosed patients, 67% had PAH and 28.3% had CTEPH. In the PAH group, 40.9% of patients had idiopathic arterial PAH (IPAH), 36.6% had PAH associated with simple congenital heart disease (PAH-CHD), 19.3% had PAH associated with systemic connective tissue disease (PAH-CTD), 1.8% had portal pulmonary hypertension (PoPH), 0.6% had PAH associated with HIV infection (PAH-HIV), 0.4% had heritable PAH (HPAH), and 0.4% had drug/toxin-induced PAH. At the time of diagnosis, PAH patients were younger than patients with CTEPH (45.2 ± 14.9; 52.6 ± 15.3 years, respectively) (p < 0.05). At the time of diagnosis, 71% PAH and 77% CTEPH patients had WHO FC III/IV. Mean (±SD) 6MWD was significantly less in CTEPH vs. the PAH group 331.3 ± 110.3 vs. 361.8 ± 135.7 m (p = 0.0006). Echo data showed a comparable sPAP between groups; CTEPH population had a more pronounced increase in the area of the right atrium (SRA) (24 [20; 32] cm2 and 19 [15; 26] cm2, respectively), and a significant decrease in FAC (24.7 [22, 4; 29.0] and 29.0 [23.0; 31.0] %, respectively) as compared to the PAH group. RHC showed a comparable increase of sPAP and mPAP in PAH and CTEPH groups. 15.2% of patients with IPAH and HPAH demonstrated positive results in the acute vasoreactivity testing. CTEPH patients were more often obese and suffered from arterial hypertension and right heart failure. Deep venous thrombosis was significantly more often observed in patients with CTEPH (53%). The most common concomitant pathology was erosive-ulcerative lesion of the stomach/duodenum, less often of the esophagus (23.5% and 44.5%, respectively). CONCLUSION: According to the Russian registry in patients with PAH and IPAH, the diagnosis is established at a younger age in comparison with the European registries. CTEPH patients are characterized by more severe functional status, pronounced signs of right heart failure taking into account the older age and the spectrum of comorbid pathology, which limits the possibility of surgical treatment. An increase in the number of expert centers participating in the registry is the key to improving early diagnosis of PH and optimal follow-up according to common standards in order to timely optimize therapy and reduce mortality of patients.

Hypotensive effect of Oxacom® containing a dinitrosyl iron complex with glutathione: animal studies and clinical trials on healthy volunteers.

A comparative study of hypotensive effects of binuclear forms of dinitrosyl iron complexes (DNICs) with glutathione, S-nitrosoglutathione (GS-NO) and sodium nitrite (NaNO(2)) on rats has been carried out. The latter appeared to be the least efficient, viz., mean arterial pressure (MAP) decreased by 10 and 30 mmHg at 25 and 100 µmoles/kg of NaNO(2). In contrast, DNIC and GS-NO produced an appreciable hypotensive effect when used at much lower concentrations. GS-NO reduced MAP to the same extent, viz., to 90 mmHg, on a hundredfold dose scale (from 0.4 up to 50 µmoles/kg) with subsequent restoration of MAP within the next 6-15 min. A similar effect was observed for DNIC except that the amplitude of the MAP drop was lower and the duration of hypotension was essentially greater. DNIC with glutathione were selected as a basic material for pilot-scale production of a hypotensive drug (commercial name Oxacom®). Preliminary pharmacological testing of Oxacom did not establish any adverse or deleterious side effects. Clinical trials of Oxacom® were performed on 14 healthy male volunteers in whom single intravenous infusion of the drug (5mg/kg or 0.2 µmoles/kg of DNIC, respectively) evoked a characteristic response manifested as a 3-4 min drop by 24-27 mmHg of both diastolic and systolic AP with its subsequent slow restoration within the next 8-10h. The heart rate was quickly normalized after an initial increase. Cardiac output was unchanged despite reduced cardiac filling. A comprehensive analysis of clinical and biochemical data failed to establish any significant pathological changes in these parameters. The data obtained suggest that Oxacom® can be recommended for the second phase of clinical trials.