• The change in exercise capacity, as measured by the total distance walked in six minutes [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  

• The reduction of mean pulmonary-artery pressure(mPAP)and pulmonary vascular resistance(PVR) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  
• The increase of cardiac output(CO) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  
• The increase of Peripheral Saturation of oxygen(SPO2) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  
• The change in the Borg dyspnea index(a measure of perceived breathlessness on a scale of 0 to 10, with higher values indicating more severe dyspnea) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  
• The change in World Health Organization (WHO) functional classification of pulmonary arterial hypertension (an adaptation of the New York Heart Association classification) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  
• Time from randomization to clinical worsening(defined as death, transplantation,hospitalization for PAH and worse right heart failure,acute heart failure,or vardenafil allergy,or worsening leading to discontinuation,need for epoprostenol or bosentan) [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: Yes ]
  

Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure ≥25 mmHg with a pulmonary capillary wedge pressure ≤15 mmHg measured by cardiac catheterization, is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary circulation. Irrespective of its etiologies, PAH is a serious and often progressive disorder that results in right ventricular dysfunction and impairment in activity tolerance, and may lead to right-heart failure and death. The pathogenesis of PAH is complex and incompletely understood, but includes both genetic and environmental factors that alter vascular structure and function.

In recent years, several new drugs have been developed for the treatment of pulmonary arterial hypertension (PAH), including continuous intravenous epoprostenol, inhaled iloprost, subcutaneous trepostinil, oral bosentan, and oral beraprost. In addition, there is increasing evidence for the therapeutic effectiveness of the phosphodiesterase-5 (PDE-5) inhibitor sildenafil in PAH. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide (NO) .The phosphodiesterases have different tissue distributions and substrate affinities. Interestingly, PDE-5 is abundantly expressed in lung tissue, thus offering as target molecule for PAH treatment concepts.

The three commercially available PDE-5 inhibitors (sildenafil, vardenafil, and tadalafil) are currently approved for the treatment of erectile dysfunction . These inhibitors are now receiving attention for their activity in the pulmonary vasculature. Sildenafil has been proved to improve the exercise capacity and pulmonary hemodynamics of PAH patients, however, there are few reports regarding the use of vardenafil or tadalafil on the pulmonary vasculature. Although sildenafil, vardenafil, and tadalafil act on the same enzyme, these drugs exhibit different pharmacokinetics and selectivity, and therefore may not be equally efficacious in the pulmonary vascular bed. As vardenafil has a more than 20-fold greater potency than sildenafil for inhibiting purified PDE-5, we assume that it will show more favorable clinical and side-effect profiles in treating PAH.

This is a prospective, randomized, placebo-controlled, pilot study to evaluate the efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension.