title: Usefulness of right-to-left shunting and poor exercise gas exchange for predicting prognosis in patients with pulmonary arterial hypertension.
abstract: We hypothesized that the longitudinal changes in peak oxygen uptake, ventilatory efficiency, and exercise-induced right-to-left shunting in patients with pulmonary arterial hypertension (PAH) would predict outcomes better than baseline measurements alone. Patients with PAH die prematurely. Identifying prognostic markers is critical for treating patients with PAH; however, longitudinal prognostic information of PAH is limited. We enrolled 103 patients with PAH into a long-term, prospective outcome study using serial cardiopulmonary exercise testing to measure the peak oxygen uptake, ventilatory efficiency (ratio of ventilation to carbon dioxide output at the anaerobic threshold), right-to-left shunting, and other factors in patients treated with optimal therapy. The patients were followed up for a mean of 4.7 years. During the study period, 20 patients died, and 3 underwent lung transplantation. The baseline peak oxygen uptake and ventilatory efficiency was 0.79 L/min and 49 (normal <34), respectively, reflecting severe disease. Poorer ventilatory efficiency and greater New York Heart Association classification were associated with poor outcome at baseline and at follow-up. On multivariate analysis, the persistence or development of an exercise-induced right-to-left shunt strongly predicted death or transplantation (p <0.0001), independent of the hemodynamics and all other exercise measures, including peak oxygen uptake and ventilatory efficiency. The absence of a shunt at baseline was associated with a 20% rate of nonsurvival, which decreased to 7% at follow-up. A poorer ventilatory efficiency appeared to be associated with a poor outcome in patients without a shunt. In conclusion, a persistent exercise-induced right-to-left shunt and poor ventilatory efficiency were highly predictive of poor outcomes in patients with pulmonary arterial hypertension.
authors.affiliation: Department of Medicine, Division of Cardiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA. roudiz@labiomed.org
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Oudiz
authors.forename: Raghu
authors.initials: R
authors.lastname: Midde
authors.forename: Arsen
authors.initials: A
authors.lastname: Hovenesyan
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Sun
authors.forename: Giorgio
authors.initials: G
authors.lastname: Roveran
authors.forename: James E
authors.initials: JE
authors.lastname: Hansen
authors.forename: Karlman
authors.initials: K
authors.lastname: Wasserman
mesh_terms: D005080:Exercise Test / Q000379:methods*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011652:Pulmonary Circulation; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D011669:Pulmonary Wedge Pressure / Q000502:physiology*; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014481:United States / Q000453:epidemiology
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