PAH in Systemic Sclerosis Increases Risk for Early Mortality

The majority of deaths in patients with systemic sclerosis-associated pulmonary arterial hypertension occurred within 4 years of diagnosis.

In patients with systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH), approximately 50% of deaths are PAH related, according to an article published in CHEST.

Risk factors for mortality include male sex, diffuse disease, systolic pulmonary artery pressure (PAP) on echocardiogram, mean PAP on right heart catheterization (RHC), 6-minute walk distance (6MWD), and diffusing capacity for carbon monoxide (DLCO).

SSc is an autoimmune disease typified by immune system dysfunction, vascular abnormalities, and fibrotic changes to the skin and internal organs. Up to 12% of people with SSc also have PAH, which is a leading cause of death in these individuals. However, evidence suggests that treatment may improve outcomes in this population.

Kathleen D. Kolstad, MD, PhD, of the Division of Immunology and Rheumatology, Department of Medicine at Stanford University School of Medicine in Palo Alto, California, and colleagues assessed the long-term outcomes and predictors of mortality in patients with SSc-PAH. They used PHAROS (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma), a prospective registry of people with SSc at high risk for PAH or with RHC-diagnosed PH. The investigators used Kaplan-Meier survival curves for the overall cohort and for those who died of PAH and identified predictors of mortality using multivariate Cox regression analysis. 

Of the 160 patients with SSc-PAH, survival at 1, 3, 5, and 8 years was 95%, 75%, 63%, and 49%, respectively. A total of 52% of all deaths were attributable to PAH, and 93% of those deaths occurred within 4 years of diagnosis. In contrast, long-term survivors were more likely to die of non-PAH-related causes. The highest level of risk for mortality was associated with male sex, which had a hazard ratio (HR) of 3.11, followed by diffuse disease (HR, 2.12), baseline systolic PAP on echocardiogram (HR, 1.06), mean PAP on RHC (HR, 1.03), 6MWD (HR, 0.92), and DLCO (HR, 0.65). Patients who died of PAH-related causes had significantly shorter 6MWD, lower percent-predicted DLCO, higher forced vital capacity/DLCO, and higher systolic PAP on echocardiogram.

Phosphodiesterase 5 inhibitor monotherapy was the most common therapy (57%) in the 129 patients who met the criteria for the medication analyses. Those who were started on oral therapy had better survival than those started on parenteral prostacyclin as monotherapy or in combination (P <.0001). Survival was comparable in both the oral combination and oral monotherapy groups, however. The authors noted that the use of prostacyclin likely indicates a more severe disease state at baseline, although prostacyclin may not be as effective in this population. 

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Limitations of the study included its observational nature, missing data, and the inability to validate that only an incident PAH population was included.

The authors called for further research to identify early markers and optimal treatments for patients with SSc with high risk for early PAH-related death.


Kolstad KD, Li S, Steen V, Chung L. Long-term outcomes in systemic sclerosis associated pulmonary arterial hypertension from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS) [published online May 17, 2018]. CHEST. doi:10.1016/j.chest.2018.05.002