title: Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease.
abstract: OBJECTIVE
  Pulmonary hypertension (PH) is an important cause of mortality in systemic sclerosis (SSc), where it can be isolated (pulmonary arterial hypertension [PAH]) or associated with interstitial lung disease (ILD). This study was undertaken to characterize determinants of survival among SSc patients with either type of PH who received PAH-specific therapy.
  
  
  METHODS
  Consecutive SSc patients with PAH or ILD-associated PH confirmed by right heart catheterization were included in the study. Kaplan-Meier and Cox proportional hazards models were used to compare survival between SSc patients with PAH and those with ILD-associated PH and to identify predictors of survival.
  
  
  RESULTS
  Fifty-nine patients (39 with PAH and 20 with ILD-associated PH) were identified. The majority (15 of 20 with ILD-associated PH and 27 of 39 with PAH) received an endothelin receptor antagonist as initial therapy. Median followup time was 4.4 years (range 2.7-7.4 years). Survival was significantly worse in SSc patients with ILD-associated PH than in those with PAH (1-, 2-, and 3-year survival rates 82%, 46%, and 39% versus 87%, 79%, and 64%, respectively; P < 0.01 by log rank test). In a multivariable analysis, ILD-associated PH was associated with a 5-fold increase in risk of death compared with PAH. Pulmonary vascular resistance index was also an independent predictor of mortality in the overall cohort (hazard ratio 1.05, P < 0.01) and was a significant univariable risk factor in each group separately. Type of initial PAH therapy and the use of warfarin were not related to survival.
  
  
  CONCLUSIONS
  Survival in SSc complicated by PH remains poor despite currently available treatment options. While therapy may be associated with improved survival in PAH compared with historical controls, the prognosis for patients with ILD-associated PH is particularly grim. Early diagnosis and treatment may improve outcomes since worsening hemodynamic factors were associated with reduced survival.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Mathai
authors.forename: Laura K
authors.initials: LK
authors.lastname: Hummers
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.forename: Ari
authors.initials: A
authors.lastname: Zaiman
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hassoun
authors.forename: Reda E
authors.initials: RE
authors.lastname: Girgis
mesh_terms: D000077300:Bosentan; D015331:Cohort Studies; D015897:Comorbidity; D065128:Endothelin Receptor Antagonists; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D007555:Isoxazoles / Q000627:therapeutic use; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D011687:Purines / Q000627:therapeutic use; D017466:Receptors, Endothelin / Q000502:physiology; D045743:Scleroderma, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use; D015996:Survival Rate; D013876:Thiophenes / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D010879:Piperazines; D011687:Purines; D017466:Receptors, Endothelin; D013449:Sulfonamides; D013450:Sulfones; D013876:Thiophenes; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; C106276:sitaxsentan; D000077300:Bosentan