Click on image to view larger version.

Figure 1 Evidence-based treatment algorithm. Levels of evidence A, B, and C grading according to Tables 4 and 5; inh = inhaled; iv = continuous intravenous. (1) The algorithm is restricted to patients in New York Heart Association (NYHA) functional class III or IV because they represent the largest population included in controlled clinical trials. For NYHA functional class I or II, very few data are available. In addition, the different treatments have been evaluated mainly in sporadic idiopathic pulmonary arterial hypertension (IPAH) patients, and in pulmonary arterial hypertension (PAH) associated with scleroderma or to anorexigen use. Extrapolation of these recommendations to the other PAH subgroups should be done with caution. (2) Owing to the complexity and dangers of the acute vasoreactivity tests, and to the treatment options available, it is strongly recommended that consideration be given to referral of patients with PAH to a specialized center. (3) The acute vasoreactivity test should be performed in all patients with PAH even if the greater incidence of positive response is achieved in individuals with IPAH and PAH associated to anorexigen use. (4) A positive acute response to vasodilators is defined as a drop in mean pulmonary artery pressure of at least 10 mm Hg to 40 mm Hg, with an increase or unchanged cardiac output during acute challenge with inhaled nitric oxide (NO), IV epoprostenol, or IV adenosine. (5) Sustained response to calcium channel blockers (CCBs) is defined as patients being in NYHA functional class I or II with near-normal hemodynamics after several months of treatment. (6) In patients in NYHA functional class III, first-line therapy may include oral endothelin receptor antagonists, chronic IV epoprostenol, or prostanoid analogues. Phosphodiesterase-V (PDE5) inhibitors should be considered in patients who have failed or are not candidates to other therapies. (7) Most experts consider that NYHA functional class IV patients in unstable condition should be treated with IV epoprostenol (survival improvement, worldwide experience, and rapidity of action).