Background/Purpose:  Pulmonary arterial hypertension (PAH) is a leading cause of death in patients with systemic sclerosis (SSc). Predictors of short-term mortality include male sex, age>60 years, functional class IV, and lung diffusing capacity (DLCO) <39% (1). The purpose of this study was to identify independent predictors of long-term outcomes.

Methods:  Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry is a prospective registry of SSc patients at high risk for PAH or with definite PH based on right heart catheterization within six months of enrollment. World Health Organization Group I PAH patients were included (using the strict criteria of baseline pulmonary artery pressure (PAP) >= 25 mmHg, pulmonary capillary wedge pressure <=15 mmHg, and forced vital capacity >= 65%). Baseline characteristics, time to clinical worsening (TTCW), and cause of death in the short (<1 year), medium (1-4.9 years) and long (>=5 years) term were assessed. TTCW was defined as time to death, PAH-related hospitalization, lung transplantation, parenteral prostacyclin treatment, or worsening symptoms (decrease of >15% in the 6-minute walk distance (6MWD) and worsening of functional class andaddition of PAH-specific medication). Cox proportional hazard models were used to identify the predictors of overall survival and TTCW.

Results:  A total of 167 SSc-associated PAH patients were included. The patient population was predominantly Caucasian (80%), female (90%), and had limited cutaneous SSc (72%). The 1, 3, 5, and 8-year cumulative survival rates were 95%, 76%, 64%, and 50%, respectively. The majority of patient deaths in the short and medium term were due to PAH (62% and 60%, respectively), while in the long-term were due to causes unrelated to SSc (75%), including cancer (n=2), infection (n=1), cerebrovascular disease (n=1), sudden death (n=1), and unknown (n=1). Baseline 6MWD >165 m (HR 0.38 95% CI 0.16-0.88) and % predicted DLCO >40 (HR 0.45 95% CI 0.23-0.89) were predictors of long-term survival on multivariate analysis. The median TTCW was 4.15 years (95% CI 3.07-5.94). At 1, 3, 5, and 8 years the percentage of patients meeting criteria for clinical worsening was 23%, 40%, 57%, and 70%, respectively. Mean PAP (mPAP) >34 mmHg (HR 2.09 95% CI 1.16-3.79) and pulmonary vascular resistance (PVR) >4.76 WU (HR 2.04 95% CI 1.14-3.68) were predictive of progression to clinical worsening.

Conclusion:  This is the longest-term prospective study to date evaluating outcomes in a US based multi-center cohort of patients with SSc-associated PAH. These data suggest that if PAH is well-controlled in the first several years after diagnosis, SSc patients have favorable outcomes, and typically die of causes unrelated to SSc. PVR and mPAP can predict progression to clinical worsening while 6MWD and % predicted DLCO values at the time of diagnosis predict long-term survival in this population. Reference: Chung L et al. Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry. Arthritis Care Res. 2014 66(3): 489–95.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/predictors-of-long-term-outcomes-in-systemic-sclerosis-associated-pulmonary-arterial-hypertension-from-the-pulmonary-hypertension-assessment-and-recognition-of-outcomes-in-scleroderma-registry/