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Original Research: Pulmonary Vascular Disease |

Baseline and Follow-up 6-Min Walk Distance and Brain Natriuretic Peptide Predict 2-Year Mortality in Pulmonary Arterial HypertensionMortality in Pulmonary Arterial Hypertension

Jason S. Fritz, MD; Christiana Blair, MS; Ronald J. Oudiz, MD, FCCP; Christopher Dufton, PhD; Horst Olschewski, MD, FCCP; Darrin Despain, MS; Hunter Gillies, MD; Steven M. Kawut, MD, FCCP
Author and Funding Information

From the Pulmonary, Allergy, and Critical Care Division (Drs Fritz and Kawut), Department of Medicine, and Penn Cardiovascular Institute (Drs Fritz and Kawut), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Gilead Sciences Inc (Ms Blair, Mr Despain, and Dr Gillies), Foster City, CA; Los Angeles Biomedical Research Institute (Dr Oudiz), Harbor-UCLA Medical Center, Torrance, CA; Rubicon Sciences LLC (Dr Dufton), Nederland, CO; Department of Internal Medicine, Division of Pulmonology (Dr Olschewski), Medical University of Graz, Graz, Austria; and Center for Clinical Epidemiology and Biostatistics (Dr Kawut), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Correspondence to: Steven M. Kawut, MD, FCCP, Perelman School of Medicine, University of Pennsylvania, 718 Blockley Hall, 423 Guardian Dr, Philadelphia, PA 19104; e-mail: kawut@upenn.edu


For editorial comment see page 285

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This work was supported by the National Institutes of Health [K24 HL103844 to S. M. K.].


Chest. 2013;143(2):315-323. doi:10.1378/chest.12-0270
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Background:  Six-minute walk distance (6MWD) and brain natriuretic peptide (BNP) levels at baseline and after initiation of treatment have been associated with survival in patients with pulmonary arterial hypertension. Our objective was to determine the individual and additive ability of pretreatment and posttreatment 6MWD and BNP to discriminate 2-year survival in patients with pulmonary arterial hypertension.

Methods:  We included patients enrolled in two randomized clinical trials of ambrisentan who had 2-year follow-up (N = 370). 6MWD and BNP were assessed before and after 12 weeks of treatment. Receiver operating characteristic curve analyses were performed to identify optimal cutoffs that defined subgroups with a high 2-year mortality. Classification and regression tree analysis was used to determine the incremental prognostic value of combined assessments.

Results:  6MWD at baseline and after 12 weeks of therapy were similarly discriminatory of 2-year survival (c-statistics = 0.77 [95% CI 0.70-0.84] and 0.82 [95% CI 0.75-0.88], respectively), whereas change in 6MWD from baseline to week 12 was not discriminating. The same observation was true of BNP at baseline and after 12 weeks of therapy (c-statistics = 0.68 [95% CI 0.60-0.76] and 0.74 [95% CI 0.66-0.82], respectively). After consideration of baseline 6MWD, there was no prognostic information added by the week 12 6MWD or BNP at either time point.

Conclusions:  6MWD and BNP values at baseline or week 12 identified a population with an elevated risk of death at 2 years. A repeat assessment of 6MWD or BNP after 12 weeks of ambrisentan therapy did not provide additional prognostic information beyond that obtained from baseline values.

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