Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: impact of pulmonary arterial hypertension therapies

Arthritis Rheum. 2011 Aug;63(8):2456-64. doi: 10.1002/art.30423.


Objective: Precapillary pulmonary hypertension (PH) is an important cause of death in patients with systemic sclerosis (SSc). It can occur in isolation (pulmonary arterial hypertension [PAH]) or in association with interstitial lung disease (ILD). Importantly, the outcomes and efficacy of PAH therapies in patients with SSc-related PH complicating ILD (PH-ILD) remain unknown. This study was undertaken to evaluate our experience with PH-ILD with regard to the efficacy and safety of PAH therapies in this patient cohort.

Methods: We conducted a retrospective analysis of consecutive SSc patients from 2 large referral centers who had PH-ILD confirmed by right-sided heart catheterization and who received targeted PAH therapies. World Health Organization (WHO) functional class, 6-minute walk distance, and hemodynamic parameters were assessed at baseline and after a mean ± SD of 7.7 ± 6.2 months of treatment for PAH. Kaplan-Meier and Cox proportional hazards models were used to analyze survival and to identify prognostic factors.

Results: Seventy patients were included in the study. No significant changes were observed in WHO functional class, 6-minute walk distance, or hemodynamic parameters after therapy. The 1-, 2-, and 3-year survival estimates were 71%, 39%, and 21%, respectively. In the multivariate model, worsening oxygenation during followup and reduced renal function were the only significant risk factors for death.

Conclusion: This study represents the largest series to date in which the impact of PAH therapies in SSc-related PH-ILD was examined. In this cohort, PAH therapies were associated with no clear benefits. Deterioration in oxygenation was an important determinant of long-term survival. Prospective clinical trials focusing on this group of patients are warranted.

MeSH terms

  • Adult
  • Aged
  • Female
  • Hemodynamics
  • Humans
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / physiopathology
  • Lung Diseases, Interstitial / etiology*
  • Lung Diseases, Interstitial / physiopathology
  • Male
  • Middle Aged
  • Registries
  • Retrospective Studies
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / physiopathology