Background/Purpose:   Interstitial lung disease (ILD) is the leading cause of death in scleroderma and is often accompanied by secondary pulmonary hypertension (Group 3 PH).  The objectives of this study were to characterize the Group 3 PH population of PHAROS, compare them to those with Group 1 PH (pulmonary arterial hypertension), and identify specific variables with prognostic significance.

Methods:   PHAROS is a prospective multi-center registry of scleroderma patients at high risk for, or with definite PH based on right heart catheterization (RHC) within six months of enrollment.  In this study, we included those considered by PHAROS investigators to have Group 3 PH as defined by the presence of moderately-severe ILD (as determined by a forced vital capacity [FVC] < 65% predicted and/or significant ILD by chest computed tomography scan) along with RHC-confirmed mean pulmonary artery pressure of ≥ 25 mmHg and pulmonary capillary wedge pressure < 15 mmHg and compared them to PHAROS subjects considered to have Group 1 PH (pulmonary arterial hypertension).  Baseline demographics and clinical characteristics at the time of RHC were assessed, and univariate analyses (STATA, version 14.0) were performed to identify variables predictive of outcome. 

Results:   Sixty-three Group 3 PH patients were identified.  Baseline demographics and clinical characteristics are displayed in the Table.  Patients with Group 3 PH were more likely to be African-American, have diffuse skin involvement, anti-Scl70 positivity and more severe impairment on pulmonary function testing, but with better cardiac hemodynamics.  With a median follow-up period of 913 days (interquartile range 383, 2158), 41% of the Group 3 PH cohort expired; with ILD progression as the most frequent cause of death (12 of 26, 46%).  The 5-year survival was similarly poor for both groups: Group 1 PH 58% vs. Group 3 PH 61%.   On univariate analysis of Group 3 PH patients, the only variable associated with survival time, was FVC (HR 0.967, 95% CI: 0.939-0.997; p=0.03):  the lower the FVC, the higher the risk of death.

Conclusion:   Moderate-severe ILD with concomitant PH is associated with a poor prognosis and the degree of physiologic restriction, as measured by FVC, is associated with worse survival time. 

*p<0.01 ** p<0.001 Categorical values are expressed as median (interquartile range) unless otherwise specified