Open Access Open Badges Research article

The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study

Vivek Thakkar1234, Wendy Stevens1, David Prior1, Peter Youssef5, Danny Liew6, Eli Gabbay7, Janet Roddy8, Jennifer G Walker9, Jane Zochling10, Joanne Sahhar11, Peter Nash12, Susan Lester13, Maureen Rischmueller13, Susanna M Proudman14 and Mandana Nikpour12*

Author Affiliations

1 Department of Rheumatology, St Vincent’s Hospital Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065, Australia

2 Department of Medicine, St Vincent’s Hospital Melbourne, The University of Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065, Australia

3 Department of Rheumatology, Liverpool Hospital, Elizabeth Street, Liverpool, NSW 2170, Australia

4 School of Medicine, University of Western Sydney, Locked bag 1797, Penrith, NSW 2751, Australia

5 Institute of Rheumatology and Orthopaedics, Royal Prince Alfred Hospital, Queen Elizabeth II building, Missendon Road, Camperdown, NSW 2050, Australia

6 Department of Epidemiology, Biostatistics and Health Research, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050, Australia

7 Pulmonary Hypertension Service and Lung Transplantation Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6001, Australia

8 Department of Rheumatology, Royal Perth Hospital, Wellington Street, GPO Box X2213, Perth, WA 6001, Australia

9 Department of Rheumatology, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042, Australia

10 Department of Rheumatology, The Menzies Institute, Private Bag 23, Hobart, TAS 7001, Australia

11 Department of Rheumatology, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, VIC 3168, Australia

12 Sunshine Coast Rheumatology, Maroochydore, PO Box 368, Sunshine Coast, QLD 4558, Australia

13 Rheumatology Department, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011, Australia

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

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Arthritis Research & Therapy 2013, 15:R193  doi:10.1186/ar4383

Published: 19 November 2013



Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH.


We evaluated our proposed algorithm (PFT with NT-proBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).


Overall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8%, respectively.


The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies.