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The patient with the verified diagnosis of idiopathic pulmonary hypertension, negative acute vasoreactivity testing by RHC, functional class III (WHO) was treated by phosphodiesterase type 5 inhibitor sildenafil. After one year there was achieved the significant improvement of the functional and hemodynamic status.

The key component of the pathogenesis of pulmonary hypertension (PH) is endothelial dysfunction with imbalance between vasodilators and vasoconstrictors and activation of the blood coagulation system. Randomized trials showed a beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on vascular remodelling and vasodilatation in pulmonary arterial hypertension (PAH). Sildenafil is the only PDE-5 inhibitor that is officially approved by Pharmacological Commitee in our country. PDE-5 inhibitors by blocking the breakdown of cyclic guanosinemonophosphate (cGMP) resulted in prolongation of the action of vasoactive mediators including nitric oxide (NO) that cause vasodilation and antiproliferation in the lung. Sildenafil demonstrated the efficacy in uncontrolled clinical studies in pts with idiopathic pulmonary hypertension, PAH due to systemic connective tissue disease, congenital heart defects, with pulmonary embolism. 25-75mg at doses 2-3 times a day in patients with improved pulmonary hemodynamics, exercise tolerance. Basis for the authorization of this drug in the setting of PAH was a large randomized, placebo-controlled trial in which different doses of sildenafil were assessed in 278 patients presenting with idiopathic PAH, PAH related to connective tissue disease or congenital systemic to pulmonary shunts surgically corrected. After three months of treatment significant hemodynamic and functional class improvements were noted in every sildenafil group as compared to placebo. An approved dose is 20 mg three times a day, but in clinical practice often higher doses of 40-80 mg to 3 times per day are in need. Stable long-term efficacy of Sildenafil was observed with the dose of 80 mg 3 times a day in SUPER-2 trial. PACES trial demonstrated the efficacy of sildenafil in combination with intravenous epoprostenol.

The currentguidelines on chronic thromboembolic pulmonary hypertension (CTEPH) treatment consider pulmonary thrombendarterectomy as the first therapy choice. In case of inoperability due to severe patient's condition, distal lesions of pulmonary vessels, extremely high pulmonary vascular resistance, medical treatment for CTEPH includes life-long anticoagulation therapy and reduction of heart failure symptoms. This clinical case of the 59-y-old patient M. with inoperable CTEPH demonstrates the efficacy of phosphodiеsterase-5 inhibitor Sildenafil usedin high doses. The diagnosis was confirmed by the results of the complete diagnostic process including right heart catheterization and pulmonary angiography. The initial functional class was assessed as III in accordance with WHO classification. Sildenafil 60 mg daily was added tothe standard therapy (anticoagulant, calcium channel blocker) for initial four weeks. To the 4wk visit Sildenafil dose was increased to 240 mgdailytaking into account good tolerance of the treatment.The significant improvement of functional class, positive dynamic ofhemodynamic and echo parameters were found to 4 month of follow-up.

The patient with the verified diagnosis of idiopathic pulmonary hypertension, functional class III (WHO) was treated by anticoagulants, diuretics, calcium channel blocker. After one year of adding endothelin receptor antagonist bosentan there was noticed the negative dynamic with right heart chambers dilation, appearing of heart failure signs. By 11 months of the combined pathogenetic therapy with bosentan and phosphodiesterase type 5 inhibitor sildenafil there was achieved the significant improvement of the functional and hemodynamic status. This positive dynamics remained within the next 3 years of observation.