Structural and functional changes in the vascular wall and thrombus formation are the main factors responsible for increased pulmonary vascular resistance (PVR) in patients with pulmonary hypertension (PH). The contribution of each of these factors is thought to be different among the variables underlying the causes of PH, thereby accounting for the varying responses to treatment with vasodilata-tive and antiproliferative agents in patients with PH of different etiology. Accordingly, pulmonary vasodilator agents have been used primarily for the treatment of patients with pulmonary arterial hypertension (PAH) and to a lesser extent in those patients with chronic thromboembolic PH (CTEPH) because of the notion that the fibrous organization of thrombotic material in the proximal vessel wall would block the vasodilator effect.
Nakayama and coworkers suggested the use of pulsatility indexes to distinguish between proximal and distal pulmonary arterial involvement. They showed that patients with CTEPH have higher pulmonary artery pulse pressures (PPs) [systolic — diastolic pressure] and lower mean pulmonary artery pressures (MPAPs) compared to patients with PAH, suggesting decreased proximal pulmonary arterial compliance and a less pronounced distal vessel involvement. However, these hemodynamic differences could not be confirmed in a 2002 cohort. Castelain et al explained their results by a secondary increase in vascular resistance at the level of small pulmonary arteries in patients with end-stage CTEPH, and suggested a common pathophysiologic mechanism between end-stage CTEPH and end-stage PAH. This new theory is supported by the histologic examination of small pulmonary vessels in CTEPH patients, which has indicated that the morphology of the vessels not affected by thrombotic occlusion is similar to that in PAH patients, as well as by other clinical trials, which have shown a favorable effect of vasodilator treatment not only in patients with PAH but also in those with CTEPH. To test this new concept, we conducted acute vasoreactivity testing using inhaled nitric oxide (iNO) and inhaled iloprost (ilLO) in patients with PAH and CTEPH (World Health Organization [WHO] functional class III to IV) during their initial diagnostic right heart catheterization.