Open Access Open Badges Research article

Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

Gene-Siew Ngian1, Wendy Stevens2, David Prior3, Eli Gabbay4, Janet Roddy5, Ai Tran5, Robert Minson6, Catherine Hill7, Ken Chow8, Joanne Sahhar9, Susanna Proudman8 and Mandana Nikpour12*

Author Affiliations

1 Department of Medicine, The University of Melbourne, Melbourne, VIC 3010, Australia

2 Department of Rheumatology, St. Vincent's Hospital Melbourne, 41 Victoria Pde, Fitzroy, VIC 3065, Australia

3 Department of Cardiology, St. Vincent's Hospital Melbourne, 41 Victoria Pde, Fitzroy, VIC 3065, Australia

4 Advanced Lung Disease Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6001, Australia

5 Department of Rheumatology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6001, Australia

6 Department of Cardiovascular Medicine, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042, Australia

7 Department of Rheumatology, The Queen Elizabeth Hospital, 28 Woodville Rd., Woodville South, SA 5011, Australia

8 Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia

9 Department of Rheumatology, Monash Medical Centre, 246 Clayton Rd., Clayton, VIC 3168, Australia

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Arthritis Research & Therapy 2012, 14:R213  doi:10.1186/ar4051

Published: 5 October 2012



Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.


Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.


Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.


In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.

Connective tissue disease; mortality; prognosis