title: Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure.
abstract: OBJECTIVE
  Borderline pulmonary arterial hypertension (PAH), characterized by a marked exercise-induced increase in pulmonary artery pressure (PAP) with normal resting values, may precede overt PAH in systemic sclerosis (SSc). We undertook the present study to investigate whether PAH treatment is safe in these patients and might attenuate hemodynamic progression.
  
  
  METHODS
  SSc patients with borderline PAH underwent right heart catheterization at baseline, after a 12-month observation period, and subsequently after 6 months of bosentan therapy. Changes in mean PAP at 50W during the observation period versus during therapy were compared.
  
  
  RESULTS
  Ten patients completed the study. Mean PAP at rest, at 50W, and during maximal exercise increased significantly during the observation period (mean ± SD increases of 2.5 ± 3.0 mm Hg [P = 0.03], 4.0 ± 2.9 mm Hg [P = 0.002], and 6.8 ± 4.1 mm Hg [P = 0.0005], respectively) and tended to decrease during the treatment period (decreases of 2.5 ± 3.9 mm Hg [P = 0.07], 1.5 ± 4.5 mm Hg [P = 0.32], and 1.8 ± 7.0 mm Hg [P = 0.43], respectively). The changes during the observation period versus the therapy period were significantly different (P = 0.03 at rest, P = 0.01 at 50W [primary end point], and P = 0.02 during maximal exercise). The changes in resting pulmonary vascular resistance were also significantly different during the observation period (increase of 8 ± 25 dynes · seconds · cm(-5) ) versus during the therapy period (decrease of 45 ± 22 dynes · seconds · cm(-5) ) (P < 0.0005). Changes in resting pulmonary arterial wedge pressure were not significantly different between the observation period and the treatment period, despite the significant increase during the observation period (2.6 ± 2.5 mm Hg [P = 0.01]). No relevant adverse effects were reported.
  
  
  CONCLUSIONS
  In SSc patients with borderline abnormal pulmonary hemodynamics, resting and exercise PAP may increase significantly within 1 year of observation. Bosentan might be safe and effective to attenuate these changes. Randomized controlled trials are warranted to confirm the exploratory findings of this hypothesis-generating pilot study.
authors: Medical University of Graz, Graz, Austria. gabor.kovacs@klinikum-graz.at
authors: Gabor
authors: G
authors: Kovacs
authors: Robert
authors: R
authors: Maier
authors: Elisabeth
authors: E
authors: Aberer
authors: Marianne
authors: M
authors: Brodmann
authors: Winfried
authors: W
authors: Graninger
authors: Xhylsime
authors: X
authors: Kqiku
authors: Stefan
authors: S
authors: Scheidl
authors: Natascha
authors: N
authors: Tröster
authors: Christian
authors: C
authors: Hesse
authors: Lewis
authors: L
authors: Rubin
authors: Horst
authors: H
authors: Olschewski
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects*; D000077300:Bosentan; D006328:Cardiac Catheterization / Q000009:adverse effects*; D005080:Exercise Test; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D010865:Pilot Projects; D012595:Scleroderma, Systemic / Q000150:complications*; D013449:Sulfonamides / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan