Background/Purpose: Pulmonary arterial hypertension (PAH) still holds a poor prognosis in patients with connective tissue diseases (CTD), especially those with systemic sclerosis (SSc). A variety of pulmonary vasodilators are currently available, but treatment regimen should be optimized based on risk for poor outcomes in individual patients. The 2015 ESC/ERS guidelines recommended the use of risk assessment based on variables to predict prognosis. The simplified version of the risk assessment using 6 variables that stratify the patients into low, intermediate, and high risk groups has been validated in large cohorts of PAH patients. However, utility of this risk stratification strategy in patients with CTD-PAH has not been established. The present study evaluated risk stratification approaches in patients with CTD-PAH using our database.

Methods: This study enrolled 61 consecutive patients who were diagnosed as having CTD-PAH at Keio University Hospital between 2000 and 2014 and Nippon Medical School Hospital between 2014 and 2019. All clinical information had been prospectively recorded on the database. Six variables, including WHO functional class (WHO-FC), 6 minutes walking distance, BNP/NT-proBNP, right atrial pressure, cardiac index (CI), and mixed venous oxygen saturation at PAH diagnosis were used to categorize the patients into 3 risk groups. The cut-off values and the risk grading were determined according to the 2015 ESC/ERS guidelines. Survival curves were obtained using Kaplan-Meier method and cumulative survival rates were compared by log-rank test.

Results: Baseline characteristics of the enrolled patients included 98% female, age at PAH diagnosis of 51 ± 18, 64% WHO-FC III/IV, and mean pulmonary arterial pressure of 45 ± 10 mmHg. Underlying CTDs were SSc in 33%, systemic lupus erythematosus in 30%, mixed connective tissue disease in 13%, and primary Sjogren’s syndrome in 15%. Risk stratification using the standard approach failed to stratify cumulative survival rates in 3 risk groups (Figure 1). When individual variables were used to stratify patients into 3 risk groups, survival rates were significantly different between patients with low risk and intermediate or high risk judged based on WHO-FC (P = 0.016 and 0.011), and between patients with low or intermediate risk and high risk judged based on CI (P = 0.009 and 0.018). Therefore, we modified the original stratification approach by weighting WHO-FC and CI for dividing the patients into the risk groups. Specifically, risk was judged to be low if WHO-FC was I or II, and high if CI was < 2.0 L/min/m2, regardless of the risk of other variables. The modified version successfully separated survival curves of 3 risk groups, and survival rates were significantly different between high risk group and low or intermediate risk group (P < 0.001 and 0.025) (Figure 2). Principally concordant results were observed in SSc-PAH sub-population.

Conclusion: The simplified 2015 ESC/ERS PAH risk stratification using 6 variables at baseline failed to predict prognosis of patients with CTD-PAH accurately. The modified approach weighting WHO-FC and CI might be useful to discriminate survival rates among risk groups, but it should be verified using independent patient cohorts.

ACR 2019 Shirai Y Figure 1

ACR 2019 Shirai Y Figure 2

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-assessment-in-connective-tissue-disease-associated-pulmonary-arterial-hypertension/